. 2015 Nov 22:3:79-85.

doi: 10.1016/j.ebiom.2015.11.037. eCollection 2016 Jan.

Reduced Human Leukocyte Antigen (HLA) Protection in Gulf War Illness (GWI)

Apostolos P Georgopoulos¹, Lisa M James², Margaret Y Mahan³, Jasmine Joseph³, Angeliki Georgopoulos⁴, Brian E Engdahl⁵

Affiliations

¹ Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN 55455, USA; Graduate Program in Biomedical Informatics and Computational Biology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: omega@umn.edu.
² Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA; Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN 55455, USA.
³ Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA; Graduate Program in Biomedical Informatics and Computational Biology, University of Minnesota, Minneapolis, MN 55455, USA.
⁴ Metabolic Service, Department of Medicine, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA; Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
⁵ Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN 55455, USA; Department of Psychology, University of Minnesota, Minneapolis, MN 55455, USA.

PMID: 26870819
PMCID: PMC4739436
DOI: 10.1016/j.ebiom.2015.11.037

Reduced Human Leukocyte Antigen (HLA) Protection in Gulf War Illness (GWI)

Apostolos P Georgopoulos et al. EBioMedicine. 2015.

. 2015 Nov 22:3:79-85.

doi: 10.1016/j.ebiom.2015.11.037. eCollection 2016 Jan.

Authors

Apostolos P Georgopoulos¹, Lisa M James², Margaret Y Mahan³, Jasmine Joseph³, Angeliki Georgopoulos⁴, Brian E Engdahl⁵

Affiliations

¹ Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN 55455, USA; Graduate Program in Biomedical Informatics and Computational Biology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: omega@umn.edu.
² Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA; Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN 55455, USA.
³ Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA; Graduate Program in Biomedical Informatics and Computational Biology, University of Minnesota, Minneapolis, MN 55455, USA.
⁴ Metabolic Service, Department of Medicine, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA; Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
⁵ Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN 55455, USA; Department of Psychology, University of Minnesota, Minneapolis, MN 55455, USA.

PMID: 26870819
PMCID: PMC4739436
DOI: 10.1016/j.ebiom.2015.11.037

Abstract

Background: Gulf War Illness (GWI) is a disease of unknown etiology with symptoms suggesting the involvement of an immune process. Here we tested the hypothesis that Human Leukocyte Antigen (HLA) composition might differ between veterans with and without GWI.

Methods: We identified 144 unique alleles of Class I and II HLA genes in 82 veterans (66 with and 16 without GWI). We tested the hypothesis that a subset of HLA 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 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). 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 protection (i.e. genetic susceptibility) in veterans with GWI.

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

Keywords: Genetic risk; Gulf War Illness (GWI); Human Leukocyte Antigen (HLA); Veterans.

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Figures

**Fig. 1**
ROC curve of classification by the six discriminating alleles. AUC, Area Under the Curve. The asymptotic standard error of the AUC was 0.062; P = 0.00004; 95% confidence intervals for the AUC: 0.708–0.953.

**Fig. 2**
Mean GWI symptom severity is plotted against the average number of copies of the six discriminating alleles. N denotes the number of participants. (See text for details.)

**Fig. 3**
Mean (± SEM, N = 6 alleles) frequency of the six discriminating alleles (combined) for the five groups indicated.

**Fig. 4**
Mean ln( $\hat{ω}$ ) (± SEM) for the control and GWI groups across the three databases. (See text for details.)

**Fig. 5**
Mean ln( $\hat{ω}$ ) for the control and GWI groups for each database. (See text for details.)

See this image and copyright information in PMC

Comment in

Towards a Biopsychosocial Model of Gulf War Illness?
Wojcik W, Lawrie SM. Wojcik W, et al. EBioMedicine. 2015 Dec 23;3:6-7. doi: 10.1016/j.ebiom.2015.12.021. eCollection 2016 Jan. EBioMedicine. 2015. PMID: 26870810 Free PMC article. No abstract available.

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References

1. Blackwell J.M., Jamieson S.E., Burgner D. HLA and infectious diseases. Clin. Microbiol. Rev. 2009;22:370–385. - PMC - PubMed
1. Broderick G., Ben-Hamo R., Vashishtha S. Altered immune pathway activity under exercise challenge in Gulf War Illness: an exploratory analysis. Brain Behav. Immun. 2013;28:159–169. - PubMed
1. Broderick G., Fletcher M.A., Gallagher Exploring the diagnostic potential of immune biomarker coexpression in Gulf War Illness. Methods Mol. Biol. 2012;934:145–164. - PubMed
1. Cano P., Klitz W., Mack S.J. Common and well-documented HLA alleles: report of the Ad-Hoc committee of the American society for histocompatiblity and immunogenetics. Hum. Immunol. 2007;68:392–417. - PubMed
1. Craddock T.J., Harvey J.M., Nathanson L., Barnes Z.M., Klimas N.G., Fletcher M.A. Using gene expression signatures to identify novel treatment strategies in gulf war illness. BMC Med. Genomics. 2015;8 (36–015-0111-3) - PMC - PubMed

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Reduced Human Leukocyte Antigen (HLA) Protection in Gulf War Illness (GWI)

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