Histological spectrum of mycophenolate mofetil-related colitis: association with apoptosis.

Aims: The main purpose of this study was to define diagnostic histological characteristics of mycophenolate mofetil (MMF)-related colitis in association with crypt epithelial cell turnover.

Methods And Results: The examined material included 43 colonic biopsies from renal transplant recipients with MMF administration and persistent diarrhoea. Thirty-three cases showed MMF-related colitis, while 10 showed no significant changes. The histological findings were scored and correlated with the apoptotic index (AI) and with the proliferation rate (PR) of the crypt epithelium examined by TUNEL assay and Ki-67 immunoexpression. Ten cases of Crohn disease and 10 of ulcerative colitis were used as comparative groups. Crypt distortion and loss as well as increased apoptosis constituted the main features, their degree and combination leading either to an inflammatory bowel disease (IBD)-like (82%) or to a graft-versus-host disease-like pattern (18%). A high AI was associated more frequently with moderate and severe crypt distortion, while the values were significantly higher compared with the control groups (P < 0.01). High PR was noted in 18 of 29 (62.1%) of the cases.

Conclusions: The diagnostic hallmark of MMF-related colitis is an IBD-like histological pattern in association with increased epithelial apoptosis, while apoptotic cell death seems to be a potential pathogenetic factor of mucosa injury.