Circulating antibody and memory B-cell responses to C. difficile toxins A and B in patients with C. difficile- associated diarrhoea, inflammatory bowel disease and cystic fibrosis

Monaghan, Tanya M. and Robins, Adrian and Knox, Alan and Sewell, Herbert F. and Mahida, Yashwant R. (2013) Circulating antibody and memory B-cell responses to C. difficile toxins A and B in patients with C. difficile- associated diarrhoea, inflammatory bowel disease and cystic fibrosis. PLoS ONE, 8 (9). e74452/1-e74452/14. ISSN 1932-6203

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Abstract

C. difficile infection (CDI) is rarely reported in cystic fibrosis (CF) patients despite frequent hospitalisations and

antibiotic usage. Conversely, the prevalence of CDI in inflammatory bowel disease (IBD) has received increased

attention. We investigated components of the IgG-specific humoral immune response to C. difficile toxins A and B in

patients with C. difficile-associated diarrhoea (CDAD), IBD patients with CDI, CF patients and healthy controls.

Serum anti-toxin IgG was determined by ELISA. Circulating antigen-activated B-cells were investigated using Alexa

Fluor 488-labelled toxin A and assessed by flow cytometry. Following induction of differentiation of memory B-cells,

toxin A- and B-specific antibody secreting cells (ASCs) were quantified using ELISpot. We present the first data

showing levels of serum anti-toxin A and B antibodies were significantly higher in patients with CF (without a history

of CDI) than in CDAD patients and were stably maintained over time. Notably, the CDAD patients were significantly

older than the CF patients. We also show that circulating toxin A-specific memory B-cells (IgD-negative) can be

detected in CDAD patients [0.92 (0.09–1.78)%], and were prominent (5.64%, 1.14%) in two CF patients who were

asymptomatic carriers of C. difficile. There was correlation between toxin A- and B-specific ASCs, with significantly

higher proportions of the latter seen. In some with CDAD, high serum antibody levels were seen to only one of the

two toxins. Mucosal secretion of toxin-specific IgG was detected in an additional group of IBD patients with no history

of CDI. We conclude that enhanced and stable humoral immune responses to toxins A and B may protect CF and

some IBD patients against CDI. The impaired ability to generate strong and/or sustained toxin-specific antibody and

memory B-cell responses may increase susceptibility

Item Type: Article
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Medicine > Medical Education Unit and Medical Courses Office
Identification Number: https://doi.org/10.1371/journal.pone.0074452
Depositing User: de Sousa, Mrs Shona
Date Deposited: 22 Apr 2014 07:46
Last Modified: 16 Sep 2016 23:39
URI: http://eprints.nottingham.ac.uk/id/eprint/2982

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