Preprint Gulf War Illness Induced Sex-Specific Transcriptional Differences Under Stressful Conditions, 2025, Frank et al

Abstract
Gulf War Illness (GWI) is a multi-symptom disorder affecting 1990–1991 Persian Gulf War veterans and is characterized by post-exertional malaise, neurological symptoms, immune deregulation, and exhaustion. Causation is not understood, and effective diagnostics and therapies have not yet been developed. In this work, we analyzed stress-related, sex-specific transcriptomic shifts in GWI subjects and healthy controls through RNA sequencing of peripheral blood mononuclear cells (PBMCs).

Blood samples at baseline (T0), at maximal exertion (T1), and four hours post-exertion (T2) were analyzed. In female subjects with GWI proinflammatory processes, and in male subjects IL-12 signaling and lymphocytic activation were deregulated at T1 compared to T0. During recovery from stress, HCMV activity and microglia activation increased in female GWI subjects, and apoptotic signaling changed in males with GWI. Documented sex-specific immune deregulation warrants personalized markers and therapies. Targeting sex-specific transcriptomic markers of disease could lead to new therapies for GWI.

Link (MDPI preprint, open access)