Sex-related peripheral immune profile in ulcerative colitis: links to fatigue

This is the authors' abstract. We don't add key points for this paper.

Background: Ulcerative colitis (UC) is a chronic inflammatory disease marked by mucosal and systemic immune dysregulation. Fatigue is a common, burdensome extraintestinal symptom that often persists beyond active inflammation and affects quality of life. Sex-based differences in immune response and fatigue severity have been reported, but their mechanistic basis remain unclear. This study aimed to characterize peripheral immune profiles across UC disease stages and explore links between immunity, fatigue, and sex. Methods: Eighty-nine individuals were enrolled: active UC (A; n=29), remission (R; n=30), and healthy controls (C; n=30). Flow cytometry assessed peripheral neutrophils, monocytes, dendritic cells (DCs), and T cell subsets, alongside plasma cytokines (BDNF, TNF, IL-6, IL-18, sTREM-2). Fatigue was evaluated using the validated Inflammatory Bowel Disease Fatigue (IBD-F) questionnaire, with sex-stratified correlation analyses. Results: DCs, and Th9/Th22 cells suggested protective immune modulation. Fatigue severity correlated with specific immune subsets in a sex-dependent manner: in males, fatigue inversely correlated with classical monocytes and Th9/Th17/Tregs; in females, with NK cells and Tregs. Fatigue scores were higher in female patients. Discussion: Peripheral immune dysregulation in UC correlates with fatigue severity in a sex-specific manner. Our findings underscore the relevance of gut-brain axis signaling and highlight immune biomarkers with potential for stratified fatigue management in UC.