Infect Immun 1998;66:5462C9. IgG producing cells in CDAD biopsies. Only patients with PMC relapsed. In these patients, B/plasma cell and IgA producing cell counts (in biopsies with and without inflammatory exudates) were significantly lower (p<0.01) in mucosal samples from those who subsequently relapsed (five) than those who did not. Conclusions: A selective reduction in mucosal IgA producing cells and macrophages is associated with colonic disease in infected patients. Severe reduction in colonic IgA producing cells may predispose to recurrence of CDAD. Keywords: B cells, Clostridium difficile toxins, plasma cells, mucosal immunology, pseudomembranous colitis The bacterium is the leading infectious cause of nosocomial diarrhoea in developed countries.1C3 The disease is mediated by two secreted toxins,4 and its presentation ranges from asymptomatic carriage to life threatening and sometimes fatal pseudomembranous colitis (PMC).5C7 Despite initial adequate treatment, a considerable proportion of patients relapse, with some having Cyromazine multiple relapses.8C11 Factors reported to be associated with recurrence include previous episodes of associated diarrhoea (CDAD), increasing age, chronic renal insufficiency, high white blood counts, and impaired antibody responses to toxin A. 8,10C12 At sigmoidoscopy, PMC can be readily identified by the presence of characteristic yellow/white plaques (pseudomembranes), which are often separated from each other by mucosa that may macroscopically appear normal or erythematous.13 Histologically, the yellow/white plaques are exudates of inflammatory cells, fibrin, mucin, and cellular debris, arising from distinct areas of epithelial ulceration (volcano lesions). The lamina propria under the area of ulceration consists of a large number of inflammatory cells, of which neutrophils are prominent by routine haematoxylin and eosin staining.13,14 However, there is little information on the characterisation of other mucosal cell types in CDAD. There are a large number of T cells,15 B/plasma cells,16 and macrophages17,18 in the normal colonic lamina propria. A major function of these cells of the mucosal immune system is to facilitate the production of secretory IgA, which is transported by epithelial cells to the lumen, to provide protection against pathogenic microorganisms.19 Impaired mucosal protection via alterations in the number or function of cells in the lamina propria may lead to increased susceptibility to CDAD and/or its recurrence. Despite initial adequate treatment, a considerable proportion of patients relapse, with some having multiple relapses In our study, we have investigated mucosal populations of T cells, B/plasma cells, immunoglobulin producing cells, and macrophages in colonic biopsies of (1) patients with CDAD and PMC, (2) patients with CDAD and either absent or minimal colonic inflammation, and (3) controls. Cyromazine We show that the numbers of mucosal macrophages, B/plasma cells, and IgA producing cells are significantly reduced in patients with CDAD, with the greatest reduction in those with PMC. The numbers of lamina propria B/plasma cells and IgA producing cells were also significantly lower in biopsies of patients in whom the disease recurred, compared with those with a single episode. MATERIALS AND METHODS Study population Colonic biopsies were obtained from patients with diarrhoea (? 3 liquid motions for more than 24 hours), as part of a prospective study to investigate the role of flexible sigmoidoscopy in the management of hospitalised patients suspected to have CDAD.20 The biopsies were divided into Cyromazine four groups (ACD). Group A (n ?=? 12) comprised mucosal samples from control patients with self limiting diarrhoea whose stool tests were negative for conventional enteric pathogens (spp, spp, spand O157) and cytotoxin, and whose sigmoidoscopy was normal, as was histological examination of colonic biopsies. Group B (n ?=? 6) comprised patients with CDAD (positive stool test for cytotoxin) with absent or minimal inflammation macroscopically at sigmoidoscopy (no pseudomembranes) and on histological Rabbit polyclonal to RFP2 examination. Groups C and D (n ?=? 10) comprised patients with CDAD (confirmed by positive stool test for cytotoxin) who had.