Abstract
BACKGROUND: Gulf War Illness (GWI) is a chronic multisystemic illness found in one-third of Gulf War Veterans. The aetiology of GWI is elusive; however, is strongly associated with exposure to multiple toxic agents, environmental exposures, and prophylactic medications or vaccinations. In the literature, disruption of the immune system and the presence of inflammation have been reported in GWI. In this novel study, we report gene expression-based analysis of a panel of 785 immune function related gene markers in GWI. METHOD: Ribonucleic acid (RNA) was extracted from peripheral blood mononuclear cells (PBMCs) isolated from n = 20 Australian GWI (CDC Case Definition and Kansas Criteria, 54.4 ± 0.74 years), and n = 15 healthy control (HC, 47.47 ± 2.91 years) participants. All participants were sex-matched (100% male). RNA gene expression was quantified using the NanoString® nCounter Immune Exhaustion panel and analysed using Rosalind Bio and IPA. RESULTS: Thirty-three differentially expressed genes were identified, of which 21 were upregulated and 12 were downregulated in the GWI cohort. Upregulated genes included SIGLEC1, BPI, MMP9, RSAD2, IFIT1/2, CEACAM1/3 and were associated with metabolic and cellular stress responses, while downregulated genes were associated with T cell receptor regions and humoral immune responses. Downregulated genes included TRDV3, IGHG1, TRGV4, TRDV1/4, and IL7. Gene set analysis revealed associations between gene expression and type I interferon signalling, natural killer receptors, T cell receptors, and tumour necrosis factor signalling. Pathway analysis revealed the role of differentially expressed genes in neutrophil signalling and degranulation, toll-like receptor cascades, and the role of lipids/lipid rafts in infection. CONCLUSION: This investigation elucidates the potential role of immune dysregulation underlying GWI, emphasising the importance of immune exhaustion pathways in disease progression. Further investigations in a larger cohort may further elucidate or confirm these identified markers for potential screening or therapeutic applications in GWI.