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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.; Robins, Adrian; Knox, Alan; Sewell, Herbert F.; Mahida, Yashwant R.

Authors

Tanya M. Monaghan

Adrian Robins

Alan Knox

Herbert F. Sewell

Yashwant R. Mahida

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

Journal Article Type Article
Publication Date Sep 10, 2013
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 8
Issue 9
Article Number e74452
Institution Citation Monaghan, T. M., Robins, A., Knox, A., Sewell, H. F., & Mahida, Y. 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), doi:10.1371/journal.pone.0074452
DOI https://doi.org/10.1371/journal.pone.0074452
Publisher URL http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0074452
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0




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