Abstract
ObjectivesDespite multiple risk factors and a high rate of colonization for Clostridium difficile, the occurrence of C. difficile infection in patients with cystic fibrosis is rare. The aim of this study was to compare the prevalence of binding C. difficile toxin-specific immunoglobulin (Ig)A, IgG and anti-toxin neutralizing antibodies in the sera of adults with cystic fibrosis, symptomatic C. difficile infection (without cystic fibrosis) and healthy controls.MethodsSubclass-specific IgA and IgG responses to highly purified whole C. difficile toxins A and B (toxinotype 0, strain VPI 10463, ribotype 087), toxin B from a C. difficile toxin-B-only expressing strain (CCUG 20309) and precursor form of B fragment of binary toxin, pCDTb, were determined by protein microarray. Neutralizing antibodies to C. difficile toxins A and B were evaluated using a Caco-2 cell-based neutralization assay.ResultsSerum IgA anti-toxin A and B levels and neutralizing antibodies against toxin A were significantly higher in adult cystic fibrosis patients (n=16) compared with healthy controls (n=17) and patients with symptomatic C. difficile infection (n=16); p≤0.05. The same pattern of response prevailed for IgG, except that there was no difference in anti-toxin A IgG levels between the groups. Compared with healthy controls (toxins A and B) and patients with C. difficile infection (toxin A), sera from cystic fibrosis patients exhibited significantly stronger protective anti-toxin neutralizing antibody responses.ConclusionA superior ability to generate robust humoral immunity to C. difficile toxins in the cystic fibrosis population is likely to confer protection against symptomatic C. difficile infection. This protection may be lost in the post-transplantation setting, where sera monitoring of anti-C. difficile toxin antibody titers may be of clinical value.
Highlights
Clostridium difficile[1] is the leading worldwide infectious cause of hospital-acquired and antibiotic-associated diarrhea.The spectrum of clinical disease varies from asymptomatic colonization to fulminant colitis and death.[2]
We identified significantly higher levels of IgA anti-toxins A and B and neutralizing antibodies against toxin A in adult cystic fibrosis patients compared with healthy controls and patients with symptomatic C. difficile infection
Limited by small sample size, our findings suggest that subclinical C. difficile infection is common among patients with cystic fibrosis
Summary
The spectrum of clinical disease varies from asymptomatic colonization to fulminant colitis and death.[2] Current understanding indicates that C. difficile pathogenesis is multifactorial, dictated by pathogenic toxin production, gut microbial dysbiosis, and altered host immune and inflammatory responses.[3]. Dovepress symptoms or develop C. difficile infection.[4,5,6,7,8,9,10] Asymptomatic carriers may be protected from progression to symptomatic infection because they can mount a humoral immune response to clostridial toxins.11The main aim of this study was to investigate the prevalence of serum immunoglobulin (Ig)A and IgG antibodies to C. difficile toxins in an adult cystic fibrosis population and to determine if sera from patients with cystic fibrosis contain protective neutralizing antibodies against the toxins
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