HLA News

Immunogenetic Epidemiology of Multiple Sclerosis in 14 Continental Western European Countries

Journal of Immunological Sciences - 2021-05-18James L, Georgopoulos AP
Human leukocyte antigen, a system involved in immune response to foreign antigens and in autoimmunity, has been strongly implicated in multiple sclerosis (MS). Prior research has shown that
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
DRB1*15:01 exerts the strongest susceptibility effect, although other
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
alleles have been implicated in both susceptibility to, and protection against, MS. Here we utilized an immunogenetic epidemiological approach to evaluate correlations between the population frequencies of 127
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Class I and II alleles and the population prevalence of MS in 14 Continental Western European countries to identify an
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
profile for MS. The results of these analyses, which largely corroborated prior findings and revealed several novel and highly robust
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
associations with MS, revealed a larger number of protective
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
alleles than susceptibility alleles, particularly for
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Class I. Given the role of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
in pathogen elimination and autoimmunity, these findings point to a contributory role of exposure to pathogens in the absence of protective
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
in underlying the inflammation and autoimmunity associated with MS.

Immunogenetic Epidemiology of Dementia and Parkinson's Disease in 14 Continental European Countries: Shared
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Profiles

Journal of Immunological Sciences - 2021-04-28James L, Georgopoulos AP
Human leukocyte antigen, which is critically involved in immune response to foreign antigens and in autoimmunity, has been implicated in dementia and Parkinson's disease. Here we report on the correlations between the population frequencies of 127
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Class I and II alleles and the population prevalence of dementia and Parkinson's disease in 14 Continental Western European countries, extending previous work1,2. We used these correlations to construct and compare
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
profiles for each disease3. We found that (a) the
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
profiles of the two diseases were significantly correlated across both
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Class I and Class II alleles, (b) negative ("protective")
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
-disease correlations did not differ significantly for either
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
class, but (c) positive ("susceptibility")
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
-disease correlations were significantly higher in dementia than in Parkinson's disease for both
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
classes of alleles. These findings indicate that (a) dementia and Parkinson's disease share immunogenetic
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
-related mechanisms, (b)
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
-related protective mechanisms (presumably against pathogens) do not differ between the two diseases, but (c)
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
-related susceptibility mechanisms (presumably underlying autoimmunity) are significantly stronger in dementia than in Parkinson's disease.

Human Leukocyte Antigens
The missing link in Alzheimer's disease etiology

Health and Medicine - 2021-02-01James L, Georgopoulos AP, Charonis S
Alzheimer's disease is a huge socioeconomic burden in developed countries. Recently, viral infections such as the herpes virus have been implicated in Alzheimer's disease risk. However, it is unclear what the link between the two is. Professor Lisa M. James of the University of Minnesota, in collaboration with Dr Apostolos Georgopoulos and Dr Spyros Charonis, has utilised computational biology to implicate the Human Leukocyte Antigens as the missing piece of the puzzle.

Commentary: COVID-19 and the Path to Immunity

Journal of Immunological Sciences - 2020-11-23James L, Tsilibary EC, Charonis S, Georgopoulos AP
A recently published Viewpoint1 underscored the importance of T- and B- cell-mediated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but omitted to mention the very first step necessary to trigger those responses, namely the formation of a complex between the virus antigen and a suitably matching
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
molecule. Here, we discuss the role of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
in individual variability in immune response to SARS-CoV-2, emphasizing the implications of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
as potentially underlying sustained symptoms seen in "long-COVID", as distinguished from the severe, acute COVID-19, which is associated with "stormy" immune response.

SARS-CoV-2 Virus and
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Class II: Investigation in silico of Binding Affinities for COVID-19 Protection and Vaccine Development

Journal of Immunological Sciences - 2020-11-16Charonis S, Tsilibary EC, Georgopoulos AP
SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
-Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Class II molecule for CD4+ T cell activation by the antigen-
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
molecule complex

Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Alleles Prevent Metabolically-Induced Inflammation and Cerebrocortical Thinning in
Gulf War Illness

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.

Journal of Neurology & Neuromedicine - 2020-10-20Christova P, James L, Carpenter A, Lewis S, Engdahl B, Georgopoulos AP
Independent lines of research have demonstrated that
Gulf War Illness

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
is associated with elevated inflammatory markers, metabolic disruptions, and alterations in brain morphometry. Possessing specific Class II
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
alleles, on the other hand, has been shown to protect against
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
and to be inversely associated with symptom severity in a dose-dependent manner. The aim of the present study was to evaluate the association between C-reactive protein (CRP), a marker of inflammation, body mass index (BMI), and brain morphometry in
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
veterans with and without a protective
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
allele. Sixty-three veterans with
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
provided blood samples for evaluation of CRP and
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
, height and weight for calculating BMI, and underwent a 3T magnetic resonance imaging scan from which the volume, surface area, and cortical thickness of 68 cortical regions of interest (ROI) were determined. Results demonstrated that the CRP was highly significantly associated with BMI and cortical thinning in veterans lacking protective
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
alleles but not in those possessing a protective
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
allele. Given the role of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
in antibody production against foreign antigens, the findings suggest that persistent foreign antigens stemming from lack of immunogenetic protection against them contribute to inflammation, metabolic disruption, and cortical thinning in
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
. The findings are discussed in terms of GW-related exposures that are known to result in inflammation.

Shared
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Coverage in dementia and Parkinson's disease

Journal of Neurology & Neuromedicine - 2020-09-22James L, Georgopoulos AP
Dementia and Parkinson's disease are the two most common age-related neurodegenerative conditions. Recent studies have identified
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Class II DRB1 alleles that are protective or neutral with respect to dementia. Here we extend those findings to evaluate the association of the population frequency of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
DRB1 alleles with the prevalence of dementia and Parkinson's disease in14 Continental Western European countries. Nine
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
DRB1 alleles were identified including four that are protective against dementia (DRB1*01:01, DRB1*04:01, DRB1*13:02, DRB1*15:01), three that are neutral (DRB1*03:01, DRB1*07:01, DRB1*08:01), and two susceptibility alleles (DRB1*11:01, DRB1*04:05). Results demonstrated that the population prevalence's of dementia and Parkinson's disease are highly correlated and that the association between the nine DRB1 alleles above and the population prevalence of dementia is highly overlapping with that of Parkinson's disease. These findings suggest a common
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Class II DRB1 profile. Given the diverse role of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Class II alleles in protection from foreign antigens, autoimmunity, and, possibly, neuroprotection, the shared
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
profile between dementia and Parkinson's disease indicates that common immunogenetic mechanisms underlie the pathogenesis and manifestation of these diseases

In silico assessment of binding affinities of three dementia-protective 2
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
alleles to nine human herpes virus 3 antigens

Current Research in Translational Medicine - 2020-07-02Charonis S, James L, Georgopoulos AP10.1016/j.retram.2020.06.002
Background

Human herpes viruses (HHV) have been implicated in dementia. Class II Human Leukocyte Antigens (
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
) play a critical role in host protection from foreign antigens including herpes viruses through stimulating antibody production against them. In the present study we investigated the in silico binding affinity of 9 H HV to three Class II
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
alleles that have been found to protect against dementia: DRB1*01:01, DRB1*13:02, and DRB1*15:01.


Methods

A sliding window approach was used to partition the amino acid sequences of surface glycoproteins from HHV 1-8 into subsequences. The binding affinity of the HHV subsequences to Class II
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
surface receptor proteins was predicted using the Sturniolo method in the Immune Epitope Database and reported as a percentile rank. The binding affinity of HHV subsequences to protective alleles was compared to that of three dementia-neutral Class II
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
alleles: DRB1*03:01, DRB1*07:01, and DRB1*08:01.


Findings

Binding affinity varied widely for each
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
allele, HHV type, and HHV subsequence. The protective alleles had significantly higher binding affinity that than the neutral alleles. The largest differences in binding affinity between the protective and neutral alleles was shown for HHV-6A and HHV-6B, which had the best overall binding affinity with the protective alleles.


Interpretation

The dementia protection conferred by the three protective
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
alleles investigated here is related to their superior ability to bind and successfully eliminate HHV epitopes - in particular, HHV6 - that could otherwise cause dementia if they persisted.

Tri-Allelic
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Protection Against Dementia

Journal of Neurology & Neuromedicine - 2019-12-28James L, Georgopoulos AP
Human Leukocyte Antigen Class II DRB1*13:02 has recently been found to protect against dementia in Continental Western Europe. Here we extend those findings by evaluating the association between the population frequency of two additional Class II
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
alleles - DRB1*01:01 and DRB1*15:01 - alone and in combination with DRB1*13:02, on dementia prevalence in Continental Western Europe. Results indicated that the prevalence of dementia in 14 Continental Western European (CWE) countries significantly decreased exponentially with increasing frequency of any of the three alleles alone and in combination (P's < 0.001). When combined, the population frequency of the three alleles accounted for 67% of the variance in dementia prevalence. The combined frequency of DRB1*01:01, DRB1*13:02, and DRB1*15:01 was also significantly associated with dementia prevalence in those aged 65 years and older (P = 0.004) and with a change in dementia prevalence between 1990 and 2016 (P = 0.006). These findings, which document the protective effects of three common Class II HLA alleles on dementia prevalence in CWE, are discussed in terms of the role of HLA class II genes in pathogen elimination. More specifically, we hypothesize that dementia prevalence is higher for countries in which the population frequency of these protective alleles is low, prohibiting the successful elimination of pathogens that may play a causal role in dementia.

Dementias Caused by Persistent Pathogens and the Protective Role of
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Against them

Journal of Neurology & Neuromedicine - 2019-12-27James L, Georgopoulos AP
Dementia is a leading cause of death worldwide, representing a significant global burden. In addition to genetic and lifestyle factors that have been widely linked to dementia, pathogens are increasingly recognized as contributing to the development of dementia. Here we discuss the role of human leukocyte antigens (
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
) in maintaining brain health by facilitating the elimination of pathogens and highlight evidence suggesting that the inability to eliminate pathogens contributes to dementia. Finally, we briefly review common forms of dementia including Alzheimer's disease, vascular dementia, frontotemporal dementia, Lewy body dementia, and prion dementia in an effort to contextualize the role of persistent pathogens across the various dementia phenotypes.

In Silico Analysis of the Binding Affinities of Antigenic Epitopes of Vaccines Administered to Gulf War Veterans to Specific
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Class II Alleles Protective for
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.

Journal of Neurology & Neuromedicine - 2019-10-19Charonis S, James L, Georgopoulos AP
GWI is a chronic, multi-symptom disorder of unknown etiology affecting veterans of the 1990-91 Gulf War. We identified previously a set of 6
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
class II alleles that are protective for
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
, namely DPB1*01:01, DPB1*06:01, DQB1*02:02, DRB1*01:01, DRB1*08:11, and DRB1*13:02. Since the function of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
class II molecules is to connect with matching extracellular antigens of various pathogens (mostly viruses), as an initial step in the sequence of events leading to the development of antibodies against the matched antigen and its subsequent elimination, we hypothesized that
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
may be due, in part, to the persistence of offending antigens which could not be eliminated. We further hypothesized that such antigens were contained in the 16 vaccines administered to GW veterans against adenovirus, anthrax, botulinum, cholera, diphtheria, hepatitis B, influenza A, Japanese encephalitis, measles, meningococcus, poliomyelitis, rabies, smallpox, tetanus, typhoid, yellow fever. This hypothesis predicts that antigens present in those vaccines should have a high affinity for matching with the 6
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
class II protective alleles above. Here we tested this prediction by using the Immune Epitope DataBase (IEDB7) to determine the ranked affinity of each one of the 6
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
protective alleles to the 10 most frequently assayed epitopes of each pathogen for which a vaccine was administered. We found that our 6
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
protective alleles above collectively covered all vaccine antigens except for rubella for which all alleles above showed low binding affinity. Affinity strength varied among antigen-allele pairs, with DRB1*01:01 and DRB1*13:02 showing overall higher affinities. These two alleles also had the highest binding affinities for the anthrax antigen contained in the anthrax vaccine administered to GW veterans. These findings document a good match between the 6
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
protective alleles above and the antigens contained in the GW vaccines, and support the fundamental assumption that the
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
protection for
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
is mediated through the successful elimination of potentially harmful persistent antigens contained in those vaccines.

The
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
DRB1*13:02 Allele Protects against Dementia in Continental Western Europe

Journal of Neurology & Neuromedicine - 2019-09-09James L, Georgopoulos AP
HLA Class II DRB1*13 alleles have recently been found to protect against age-related brain deterioration, even in the presence of
Apolipoprotein E

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4 (
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4), suggesting a possible protection against dementia. Here we evaluated the association between the population frequency of common DRB1*13 alleles and the prevalence of dementia in Continental Western Europe. Prevalence of dementia in Continental Western Europe was derived from published reports on dementia frequency from the Global Burden of Disease Study 2016 and population totals obtained from the Population Reference Bureau. DRB1*13:01 and DRB1*13:02 allele frequencies were obtained from a publicly available database (allelefrequency.net) and
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
was obtained from published reports on the world distribution of
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4. The prevalence of dementia in 14 Continental Western European (CWE) countries, where life expectancy is practically identical, significantly decreases exponentially with increasing frequency of DRB1*13:02 (R2 = 0.452, P = 0.008), even when adjusted for the prevalence of
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4 allele, a known risk factor for Alzheimer's disease. This finding documents the protective effect of DRB1*13:02 on dementia prevalence in CWE. Since the function of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
class II genes is to aid in the elimination of pathogens by enabling the production of antibodies against their antigens in specific immunity, the protective effect of DRB1*13:02 points to the presence of persistent harmful antigens as causal factors in development of dementia, antigens specific to DRB1*13:02 that could not be eliminated in its absence.

Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
as a Key Factor in Preventing Dementia and Associated
Apolipoprotein E

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4 Risk

Frontiers in Aging Neuroscience - 2019-04-12James L, Georgopoulos AP10.3389/fnagi.2019.00082
Itzhaki's (2018) recent review discusses the evidence for a role of herpes virus (mainly herpes virus 1) in the development of Alzheimer's disease (AD), particularly among genetically vulnerable individuals. Specifically, the viral concept proposes that latent herpes virus in the brain of
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4 (
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4) carriers is intermittently reactivated causing cumulative damage that ultimately results in AD. The viral concept and collective findings are particularly intriguing given the potential for intervention for AD aimed at neutralizing or eliminating herpes virus. Here we discuss
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
as an additional genetic link in the viral concept of AD that not only accounts for the role of herpes virus in AD, but also extends to other viruses that may contribute to AD and to other diseases, and is consistent with beneficial brain effects of treatments aimed at eliminating the damaging effects of herpes virus via antivirals or IVIG as discussed in the review.

Persistent Antigens Hypothesis: The
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Connection

J Neurol Neuromedicine - 2018-12-24James L, Georgopoulos AP
HLA genes play a critical role in immune protection from foreign antigens including viruses, bacteria, and parasites1. Located in the Major Histocompatibility Complex (MHC) of chromosome 6,
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
genes code for glycoproteins that exist on the surface of most cells in order to facilitate immune surveillance and initiate an immune response to eliminate foreign antigens. There are two main classes of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
(Class I and Class II) that support the elimination of cytosolic or extracellular foreign antigens through cell destruction and antibody production, respectively.
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
genes have evolved to be the most highly polymorphic in the human genome, thereby maximizing species resistance to foreign antigens and promoting survival. Nonetheless, successful elimination of foreign antigens is predicated on a match between one's
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
and epitopes derived from foreign antigen proteins. Each person has a limited repertoire of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
proteins inherited in a Mendelian fashion for each class. Fortunately, each
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
protein can match with various epitopes and, since everyone has one or two alleles at each of the classical loci (Class I
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
-A, B, and C and Class II
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
-DP, DQ, and DR), a large number of antigens can be effectively eliminated.

Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
in Gulf War Veterans: Association with Symptoms and Inflammatory Markers

Defense Technical Information Center - 2018-10-01James L
During the initial year of the grant period, the primary emphasis has been on obtaining regulatory approval for study procedures, training staff and building a data repository, and initial identification and recruitment of study participants. We have obtained all regulatory approvals, created a data repository, and completed 40 acquisitions, with several additional acquisitions scheduled. We will continue to recruit at an accelerated pace to meet our recruitment goals and have identified additional recruitment avenues to maximize outreach.

Reduced
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Protection in
Gulf War Illness

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.

Background

GWI is a disease of unknown etiology with symptoms suggesting the involvement of an immune process. Here we tested the hypothesis that
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
composition might differ between veterans with and without
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
.

Methods

We identified 144 unique alleles of Class I and II
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
genes in 82 veterans (66 with and 16 without
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
). We tested the hypothesis that a subset of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
alleles may classify veterans in their respective group using a stepwise linear discriminant analysis. In addition, each participant rated symptom severity in 6 domains according to established
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
criteria, and an overall symptom severity was calculated.

Findings

We found 6 Class II alleles that classified participants 84.1% correctly (13/16 control and 56/66
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
). The number of copies of the 6 alleles was significantly higher in the control group, suggesting a protective role. This was supported by a significant negative dependence of overall symptom severity on the number of allele copies, such that symptom severity was lower in participants with larger numbers of allele copies.

Interpretation

These results indicate a reduced
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
protection (i.e. genetic susceptibility) in veterans with
GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
.

Funding

University of Minnesota and U.S. Department of Veterans Affairs.