Upregulation of Fas-Fas-L (CD95/CD95L)-Mediated Epithelial Apoptosis—A Putative Role in Pouchitis?

• Published in: The Journal of surgical research 2001-06, Vol.98 (1), p.27-32
• Main Authors: Coffey, J.C., Bennett, M.W., Wang, J.H., O'Connell, J., Neary, P., Shanahan, F., Redmond, H.P., Kirwan, W.O.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antibodies, Monoclonal; Apoptosis - physiology; Atrophy; Biological and medical sciences; Child; epithelial apoptosis; Fas Ligand Protein; fas Receptor - physiology; Fas-L; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Ileum - pathology; Ileum - physiopathology; Immunohistochemistry; In Situ Nick-End Labeling; Intestinal Mucosa - pathology; Intestinal Mucosa - physiopathology; M30; Medical sciences; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - physiology; Microvilli - pathology; Middle Aged; Other diseases. Semiology; pouchitis; Pouchitis - pathology; Pouchitis - physiopathology; Stomach, duodenum, intestine, rectum, anus; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; TUNEL; Up-Regulation; villous atrophy
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.2001.6129

Introduction. Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes considerable morbidity in 40% of patients with IPAA. This study examined the role of 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 patients who were pouchitis free. Apoptosis was detected immunohistochemically using a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL). Villous atrophy was assessed histologically and correlated with levels of apoptosis. Epithelial Fas-ligand (L) was also assessed immunohistochemically. Results. A significant increase in TUNEL staining was seen at the epithelial but not at the lamina propria level for known pouchitis patients versus controls (0.091 vs 0.035; P < 0.01). Similarly, epithelial M30 immunoreactivity (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 compared with normal pouches. Upregulation of Fas-L expression was characteristic of this epithelium. Mononuclear cells were strongly positive for Fas-L. Increased epithelial levels of apoptosis correlated with increased levels of villous atrophy. Conclusions. Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-mediated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispose to infection by otherwise apathogenic organisms.