Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis - A putative role in pouchitis?

Introduction, Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes consider able morbidity in 40% of patients with IPAA, This study examined the role o f increased epithelial apoptosis in the etiology of pouchitis. Methods. Following ethical approval pouch biopsies taken from patients with a history of pouchitis were compared with age-matched controls from patien ts who were pouchitis free, Apoptosis was detected immunohistochemically us ing a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transfera se (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL), Villous atrophy wa s assessed histologically and correlated with levels of apoptosis, Epitheli al Fas-ligand (L) was also assessed immunohistochemic ally. Results. A significant increase in TUNEL staining was seen at the epithelia l but not at the lamina propria level for known pouchitis patients versus c ontrols (0.091 vs 0.035; P < 0.01), Similarly, epithelial M30 immunoreactiv ity (0.225 vs 0.082; P < 0.05) and villous atrophy (0.035 vs 0.10; P < 0.05 ) were significantly increased in pouches with previous pouchitis when comp ared with normal pouches. Upregulation of Fas-L expression was characterist ic of this epithelium. Mononuclear cells were strongly positive for Fas-L, Increased epithelial levels of apoptosis correlated with increased levels o f villous atrophy. Conclusions. Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-me diated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispo se to infection by otherwise apathogenic organisms. (C) 2001 Academic Press .