Human Leukocyte Antigen (HLA) Alleles Prevent Metabolically-Induced Inflammation and Cerebrocortical Thinning in Gulf War Illness

Abstract

Independent lines of research have demonstrated that GWI is associated with elevated inflammatory markers, metabolic disruptions, and alterations in brain morphometry. Possessing specific Class II human leukocyte antigen (HLA) alleles, on the other hand, has been shown to protect against GWI and to be inversely associated with symptom severity in a dose-dependent manner. The aim of the present study was to evaluate the association between C-reactive protein (CRP), a marker of inflammation, body mass index (BMI), and brain morphometry in GWI veterans with and without a protective HLA allele. Sixty-three veterans with GWI provided blood samples for evaluation of CRP and HLA, height and weight for calculating BMI, and underwent a 3T magnetic resonance imaging scan from which the volume, surface area, and cortical thickness of 68 cortical regions of interest (ROI) were determined. Results demonstrated that the CRP was highly significantly associated with BMI and cortical thinning in veterans lacking protective HLA alleles but not in those possessing a protective HLA allele. Given the role of HLA in antibody production against foreign antigens, the findings suggest that persistent foreign antigens stemming from lack of immunogenetic protection against them contribute to inflammation, metabolic disruption, and cortical thinning in GWI. The findings are discussed in terms of GW-related exposures that are known to result in inflammation.

Keywords: Brain Atrophy Persistent Antigens; Gulf War Illness; Inflammation; Metabolic Human Leukocyte Antigen.

Figure 1.

Frequency distribution of BMI for the two HLA groups. (See text for details.)

Figure 2.

Frequency distribution of CRP and ln(CRP) for the two HLA groups. (See text for details.)

Figure 3.

ln(CRP) is plotted against BMI for the two HLA groups. (See text for details.)

Figure 4.

HLA-p0 group: ln(Cortical thickness) adjusted for age, gender and eTiV (mean ± SEM) is plotted against binned ln(CRP) (binwidth = 1 lnCRP unit). (See text for details.)