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.
as a neuroimmune disease

GWI is a chronic disease characterized by the involvement of several organs, including the brain (Christova et al., Exp Brain Res doi: 10.1007/s00221-017-5010-8, 2017). In a previous study (Georgopoulos et al., J Neural Eng 4:349-355, 2015), we identified six protective alleles from Class II
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.
genes, and more recently, we investigated the brain correlates of this protection (James et al., EBioMedicine 13:72-79, 2016). Those and other studies (Israeli, Lupus, 21:190-194, 2012) suggested an involvement of the immune system 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.
. In a recent study (Engdahl et al., EBioMedicine doi: 10.1016/j.ebiom.2016.08.030, 2016), we showed that the brain pattern of
Synchronous Neural Interactions

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
(
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
; Georgopoulos et al., J Neural Eng 4:349-355, 2007) 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.
is distinctly different from that in healthy controls. Here we focused on the
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
itself, as a basic measure of neural communication (irrespective of specific connections) and compared it between
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 seven other diseases that cover a broad spectrum of etiology and pathophysiology. Specifically, we sought to determine which, if any, of those diseases might resemble
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.
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
, overall and within 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.
protective domain, and thus gain further knowledge regarding the nature of
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.
brain abnormality. We studied a total of 962 participants from a healthy control population (N = 583) and eight different diseases, including
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.
(N = 40), schizophrenia (SZ; N = 21), Alzheimer's disease (AD; N = 66),
Posttraumatic Stress Disorder

Posttraumatic Stress Disorder (PTSD)

A complex psychiatric syndrome that develops in response to trauma exposure. Individuals with PTSD experience intrusive recollections or reexperiencing of the traumatic event, avoidance of trauma reminders, emotional numbing, and hyperarousal. In addition, PTSD is associated with high rates of concomitant physical and mental health problems, increased health care use, and impairment in social and occupational functioning. Almost 7% of the general population and up to 30% of veterans meet lifetime criteria for PTSD. Indeed, PTSD is one of the most common psychiatric disorders, representing a significant and costly public health concern.
(
PTSD

Posttraumatic Stress Disorder (PTSD)

A complex psychiatric syndrome that develops in response to trauma exposure. Individuals with PTSD experience intrusive recollections or reexperiencing of the traumatic event, avoidance of trauma reminders, emotional numbing, and hyperarousal. In addition, PTSD is associated with high rates of concomitant physical and mental health problems, increased health care use, and impairment in social and occupational functioning. Almost 7% of the general population and up to 30% of veterans meet lifetime criteria for PTSD. Indeed, PTSD is one of the most common psychiatric disorders, representing a significant and costly public health concern.
; N = 159), major depressive disorder (MDD; N = 10), relapsing-remitting multiple sclerosis (RRMS; N = 43), Sj"ogren's syndrome (SS; N = 32), and rheumatoid arthritis (RA; N = 8). They all underwent a resting-state magnetoencephalographic (
Magnetoencephalography

Magnetoencephalography (MEG)

A noninvasive technique that detects magnetic fields above the surface of the head produced by postsynaptic potentials in the brain.
) scan to calculate SNIs. Data were analyzed using analysis of covariance (ANCOVA) with disease as fixed factor, and sex and age as covariates. We found 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.
SNIs differed significantly from control SZ, AD,
PTSD

Posttraumatic Stress Disorder (PTSD)

A complex psychiatric syndrome that develops in response to trauma exposure. Individuals with PTSD experience intrusive recollections or reexperiencing of the traumatic event, avoidance of trauma reminders, emotional numbing, and hyperarousal. In addition, PTSD is associated with high rates of concomitant physical and mental health problems, increased health care use, and impairment in social and occupational functioning. Almost 7% of the general population and up to 30% of veterans meet lifetime criteria for PTSD. Indeed, PTSD is one of the most common psychiatric disorders, representing a significant and costly public health concern.
and MDD but not from RRMS, SS and RA. In addition, we compared
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.
to RRMS, SS and RA with respect to SNIs of
MEG

Magnetoencephalography (MEG)

A noninvasive technique that detects magnetic fields above the surface of the head produced by postsynaptic potentials in the brain.
sensor pairs that were related to 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.
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.
(James et al., EBioMedicine 13:72-79, 2016). We found 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.
SNIs did not differ significantly from any of these three diseases but they did so from control SZ, AD,
PTSD

Posttraumatic Stress Disorder (PTSD)

A complex psychiatric syndrome that develops in response to trauma exposure. Individuals with PTSD experience intrusive recollections or reexperiencing of the traumatic event, avoidance of trauma reminders, emotional numbing, and hyperarousal. In addition, PTSD is associated with high rates of concomitant physical and mental health problems, increased health care use, and impairment in social and occupational functioning. Almost 7% of the general population and up to 30% of veterans meet lifetime criteria for PTSD. Indeed, PTSD is one of the most common psychiatric disorders, representing a significant and costly public health concern.
and MDD. These findings indicate that (a)
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.
brain synchronicity does not differ significantly from that of known immune-related diseases (RRMS, SS, RA), and (b) that this
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
similarity is present within 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.
-related SNIs. In contrast,
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.
SNIs differed significantly from those of the other diseases. We conclude that altered brain communication 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.
likely reflects immune-related processes, as postulated previously (James et al., EBioMedicine 13:72-79, 2016). By extension, these findings also indicate that functional brain abnormalities in RRMS, SS and RA might be, in part, due to lack 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 as documented 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.
(Georgopoulos et al., EBioMedicine 3:79-85, 2015).