title: Humoral immune response as predictor of recurrence in Clostridium difficile infection.
abstract: Low serum concentrations of antibodies directed against the toxins TcdA and TcdB have been associated with a higher risk of recurrence of Clostridium difficile infection (CDI) after successful antibiotic treatment. However, there are conflicting reports. Herein, we compared serum levels of antibodies of patients with a single episode of CDI with those of patients who subsequently suffered a recurrence. We used a serum bank from patients who received an experimental whey protein product following successful antibiotic treatment for CDI. We determined levels of IgA and IgG directed against TcdA, TcdB and non-toxin cell surface antigens in serum collected directly and 3 weeks after completing a 10-day course of antibiotic treatment for CDI. We also developed an objective flow cytometry-based assay to determine the proportion of cells exhibiting cytopathic effect after exposure to TcdB. Using this method, we measured the TcdB-neutralizing capacity of sera. We compared the results for patients without a subsequent recurrence with those of patients who suffered a recurrence within 60 days after completing the antibiotic treatment. Advanced age, comorbidity other than immunocompromised state and low serum levels of anti-TcdA and anti-TcdB antibodies were associated with recurrence, whereas serum levels of antibodies directed against cell surface antigens were not. Serum TcdB-neutralizing capacity, which correlated only weakly with serum IgG anti-TcdB, was not significantly associated with recurrence.
authors.affiliation: Department of Infectious Diseases, Centre for Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: M P
authors.initials: MP
authors.lastname: Bauer
authors.forename: P H
authors.initials: PH
authors.lastname: Nibbering
authors.forename: I R
authors.initials: IR
authors.lastname: Poxton
authors.forename: E J
authors.initials: EJ
authors.lastname: Kuijper
authors.forename: J T
authors.initials: JT
authors.lastname: van Dissel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D016360:Clostridioides difficile / Q000276:immunology*; D003015:Clostridium Infections / Q000453:epidemiology* / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007070:Immunoglobulin A; D007074:Immunoglobulin G
keywords: Antibodies; Clostridium difficile; IgA; IgG; recurrence; toxins