Mucosal Immune Activation in Irritable Bowel Syndrome: Gender-Dependence and Association With Digestive Symptoms

OBJECTIVES: Immune activation may be involved in the pathogenesis of irritable bowel syndrome (IBS). However, the relative magnitude of this immune component and its correlation with gender and gastrointestinal complaints in IBS patients remains poorly elucidated. METHODS: We enrolled 48 IBS patients, with either diarrhea or constipation, 12 patients with microscopic colitis, 20 patients with ulcerative colitis, and 24 healthy controls. Colonic immunocytes were identified with quantitative immunohistochemistry on mucosal biopsies. Gastrointestinal symptoms were assessed using a validated questionnaire. RESULTS: IBS patients showed a significant 72% increase in mucosal immune cells compared to controls (P<0.001). Further analyses showed that increased immune cells were present in 50% of the IBS patients. The magnitude of the immune infiltrate in IBS was significantly lower than that of microscopic colitis or ulcerative colitis (42% and 124% increases vs. IBS, respectively;P<0.001). Compared with controls, IBS patients had increased numbers of CD3 +, CD4+, and CD8+ T cells and mast cells (P< 0.001). Compared to male IBS patients, female IBS patients had greater numbers of mast cells (P=0.066), but lower numbers of CD3+ and CD8 + T cells (P= 0.002 and <0.001, respectively). Mucosal mast cell infiltration of IBS patients was significantly associated with abdominal bloating frequency (P=0.022) and with symptoms of dysmotility-like dyspepsia (P=0.001), but not ulcer-like dyspepsia. CONCLUSIONS: A large subset of IBS patients shows gender-dependent mucosal infiltration of immunocytes that correlates with abdominal bloating and dysmotility-like dyspepsia. These results provide the rationale for considering immune mechanisms as a pathophysiological component in a subset of IBS patients. Am J Gastroenterol 2009; 104:392-400; doi:10.1038/ajg.2008.94; published online 13 January 2009