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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 126-131 |
| Number of pages | 6 |
| Journal | EBioMedicine |
| Volume | 26 |
| DOIs | |
| State | Published - Dec 2017 |
Bibliographical note
Funding Information:Partial funding for this study was provided by the US Department of Defense, U.S. Department of Veterans Affairs, and the University of Minnesota (Brain and Genomics Fund and the American Legion Brain Sciences Chair). 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.
Funding Information:
This work was partially supported by a service directed grant from the United States Department of Veterans Affairs, a grant for the United States Department of Defense (award number W81XWH-15-1-0520), 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:
This work was partially supported by a service directed grant from the United States Department of Veterans Affairs, a grant for the United States Department of Defense (award number W81XWH-15-1-0520 ), 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.
Publisher Copyright:
© 2017
Keywords
- Cerebellum
- DRB1*13:01
- DRB1*13:02
- Gulf War Illness
- Human Leukocyte Antigen
- Subcortical brain atrophy