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. 2017 Dec:26:126-131.
doi: 10.1016/j.ebiom.2017.11.005. Epub 2017 Nov 9.

Human Leukocyte Antigen (HLA) and Gulf War Illness (GWI): HLA-DRB1*13:02 Spares Subcortical Atrophy in Gulf War Veterans

Lisa M James  1 , Peka Christova  2 , Brian E Engdahl  3 , Scott M Lewis  4 , Adam F Carpenter  4 , Apostolos P Georgopoulos  5
Affiliations

Human Leukocyte Antigen (HLA) and Gulf War Illness (GWI): HLA-DRB1*13:02 Spares Subcortical Atrophy in Gulf War Veterans

Lisa M James et al. EBioMedicine. 2017 Dec.

Abstract

Background: Gulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-91 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. We reported previously on the protective role of six Human Leukocyte Antigen (HLA) alleles in GWI (Georgopoulos et al., 2016) and their association with regional brain function (James et al., 2016). More recently, we reported on the presence of subcortical brain atrophy in GWI (Christova et al., 2017) and discussed its possible relation to immune mechanisms. Here we focused on one of the six HLA GWI-protective HLA alleles, DRB1*13:02, which has been found to have a protective role in a broad range of autoimmune diseases (Furukawa et al., 2017), and tested its effects on brain volumes.

Methods: Seventy-six Gulf War veterans (55 with GWI and 21 healthy controls) underwent a structural Magnetic Resonance Imaging (sMRI) scan to measure the volumes of 9 subcortical brain regions to assess differences between participants with (N=11) and without (N=65) HLA class II allele DRB1*13:02.

Findings: We found that DRB1*13:02 spared subcortical brain atrophy in Gulf War veterans; overall subcortical volume was 6.6% higher in carriers of DRB1*13:02 (P=0.007). The strongest effect was observed in the volume of cerebellar gray matter which was 9.6% higher (P=0.007) in carriers of DRB1*13:02 than in non-carriers. By contrast, DRB1*13:01 had no effect.

Interpretation: These findings document the protective effect of DRB1*13:02 on brain atrophy in Gulf War veterans and are in keeping with recent results documenting sharing of brain mechanisms between GWI and other immune-related diseases (Georgopoulos et al., 2017). We hypothesize that the protective role of DRB1*13:02 is due to its successful elimination of external antigens to which Gulf War veterans were exposed, antigens that otherwise would persist causing low-grade inflammation and possibly leading to autoimmunity.

Funding source: U.S. Department of Defense (W81XWH-15-1-0520), Department of Veterans Affairs, American Legion Brain Sciences Chair, and University of Minnesota.

Keywords: Cerebellum; DRB1*13:01; DRB1*13:02; Gulf War Illness; Human Leukocyte Antigen; Subcortical brain atrophy.

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Figures

Fig. 1
Fig. 1
Mean (± SEM) subcortical volumes in the absence and presence of DRB1*13:02. Statistics are from a univariate ANCOVA where the Subcortical volume was the dependent variables, the absence or presence of DRB1*13:02 was a fixed factor, and sex, age and eTIV were covariates.
Fig. 2
Fig. 2
Mean (± SEM) volumes of cerebellar gray matter in the absence and presence of DRB1*13:02. Statistics are from a multivariate ANCOVA where the cerebellar gray matter volume (one of 9 subcortical regions; see Table 2) was a dependent variable, the absence or presence of DRB1*13:02 was a fixed factor, and sex, age and eTIV were covariates.
Fig. 3
Fig. 3
Schematic diagram illustrating the steps of antibody production in health.
Fig. 4
Fig. 4
Schematic diagram illustrating the disruption at various possible stages of antibody production leading to disease.
See this image and copyright information in PMC

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References

    1. Bettencourt A., Carvalho C., Leal B. The protective role of HLA-DRB1*13 in autoimmune diseases. J Immunol Res. 2015;948723:15. - PMC - PubMed
    1. Blake D.D., Weathers F.W., Nagy L.M. The development of a clinician-administered PTSD scale. J. Trauma. Stress. 1995;8:75–90. - PubMed
    1. Brown J.H., Jardetzky T.S., Gorga J.C. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature. 1993;364:33–39. - 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. Christova P., James L.M., Engdahl B.E. Subcortical brain atrophy in Gulf War Illness. Exp. Brain Res. 2017;235:2777–2786. - PubMed

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