Humoral immune response as predictor of recurrence in Clostridium difficile infection

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.