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

Apostolos P. Georgopoulos; Lisa M. James; Margaret Y. Mahan; Jasmine Joseph; Angeliki Georgopoulos; Brian E. Engdahl

doi:10.1016/j.ebiom.2015.11.037

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

Apostolos P. Georgopoulos, Lisa M. James, Margaret Y. Mahan, Jasmine Joseph, Angeliki Georgopoulos, Brian E. Engdahl

Neuroscience

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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.

Original language	English (US)
Pages (from-to)	79-85
Number of pages	7
Journal	EBioMedicine
Volume	3
DOIs	https://doi.org/10.1016/j.ebiom.2015.11.037
State	Published - Jan 1 2016

Bibliographical note

Funding Information:
We thank Ryan Miller PhD, Kari Resel and Alina Shub for assisting in recruiting participants and data collection, and Laura Kalipe for DNA isolation. Partial funding for this study was provided by the US Department of Veterans Affairs and the University of Minnesota (Brain and Genomics Fund and the American Legion Brain Sciences Chair). The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Funding Information:
Partial funding for this study was provided by the US Department of Veterans Affairs (Service Directed Research Program, Project Number 3106) and the University of Minnesota (Brain and Genomics Fund [University of Minnesota Foundation Fund Number 20507] and the American Legion Brain Sciences Chair [University of Minnesota Foundation Fund Number 20442]). The sponsors had no role in the current study design, analysis or interpretation, or in the writing of this paper. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Publisher Copyright:
© 2015.

Keywords

Genetic risk
Gulf War Illness (GWI)
Human Leukocyte Antigen (HLA)
Veterans

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

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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.",

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N2 - 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.

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KW - Human Leukocyte Antigen (HLA)

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

Abstract

Bibliographical note

Keywords

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