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Colonic IgA producing cells and macrophages are reduced in recurrent and non-recurrent Clostridiumdifficile associated diarrhoea

¹ Division of Gastroenterology, University Hospital, Nottingham NG7 2UH, UK
² Institute of Infection, Immunity and Inflammation, University Hospital, Nottingham
³ Department of Histopathology, University Hospital, Nottingham
⁴ Central Public Health Laboratory, Health Protection Agency London NW9 5HT, UK

Correspondence to:
Y R Mahida
Institute of Infection, Immunity and Inflammation, University Hospital, Queen’s Medical Centre, Nottingham NG7 2UH, UK; Yash.Mahida{at}Nottingham.ac.uk Background: In Clostridium difficile associated diarrhoea (CDAD), histological changes in the colonic mucosa range from minimal inflammation to pseudomembranous colitis (PMC). The disease also recurs in a considerable proportion of patients.

Aim: To investigate mucosal immune system cells in colonic biopsies of patients with CDAD.

Methods: Colonic biopsies were obtained from 12 control patients with diarrhoea, six patients with CDAD and minimal inflammation, and 10 patients with CDAD with pseudomembranous colitis (samples obtained from areas with and without inflammatory exudate). Immunohistochemical studies were performed using antibodies to T cells (CD3), macrophages (CD68), B/plasma cells (CD79), and to IgA, IgM, and IgG. Labelled cells in lamina propria were quantified.

Results: In contrast to T cells, there were significant reductions in B/plasma cell and macrophage counts in all biopsies from patients with CDAD compared with controls (p<0.001). Studies using anti-immunoglobulin antibodies showed significant reductions in IgA producing cells in CDAD biopsies (p<0.05), with the greatest reduction in samples from patients with PMC. In contrast, there was a significant increase (p<0.05) in 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 C difficile infected patients. Severe reduction in colonic IgA producing cells may predispose to recurrence of CDAD.

Abbreviations: CDAD, Clostridiumdifficile associated diarrhoea; PMC, pseudomembranous colitis

Keywords: B cells; Clostridium difficile toxins; plasma cells; mucosal immunology; pseudomembranous colitis

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