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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.
- Source :
-
PloS one [PLoS One] 2013 Sep 10; Vol. 8 (9), pp. e74452. Date of Electronic Publication: 2013 Sep 10 (Print Publication: 2013). - Publication Year :
- 2013
-
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 of older patients to CDI and highlight the need to investigate the role of immune senescence in future studies.
- Subjects :
- Adult
Antibodies, Bacterial immunology
Antibody Specificity immunology
Cell Movement immunology
Clostridium Infections blood
Clostridium Infections complications
Clostridium Infections immunology
Clostridium Infections microbiology
Cystic Fibrosis blood
Cystic Fibrosis complications
Cystic Fibrosis immunology
Diarrhea blood
Diarrhea complications
Diarrhea immunology
Enterotoxins immunology
Female
Flow Cytometry
Humans
Immunoglobulin G blood
Inflammatory Bowel Diseases blood
Inflammatory Bowel Diseases complications
Inflammatory Bowel Diseases immunology
Intestinal Mucosa immunology
Intestinal Mucosa pathology
Male
Time Factors
Young Adult
Antibodies, Bacterial blood
B-Lymphocytes immunology
Bacterial Toxins immunology
Clostridioides difficile immunology
Cystic Fibrosis microbiology
Diarrhea microbiology
Immunologic Memory immunology
Inflammatory Bowel Diseases microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24058568
- Full Text :
- https://doi.org/10.1371/journal.pone.0074452