Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis--a putative role in pouchitis?
BACKGROUND
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.
Coffey
J C
JC
Department of Academic Surgery, Cork University Hospital, Cork, Ireland.
Bennett
M W
MW
Wang
J H
JH
O'Connell
J
J
Neary
P
P
Shanahan
F
F
Redmond
H P
HP
Kirwan
W O
WO
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000502:physiology*; D001284:Atrophy; D002648:Child; D053222:Fas Ligand Protein; D006801:Humans; D007082:Ileum / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D008871:Microvilli / Q000473:pathology; D008875:Middle Aged; D019449:Pouchitis / Q000473:pathology / Q000503:physiopathology*; D015854:Up-Regulation; D019014:fas Receptor / Q000502:physiology*
D000911:Antibodies, Monoclonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor