Humoral Immune Response to Clostridioides difficile Toxins A and B in Hospitalized Immunocompromised Patients with C. difficile infection

Background The humoral immune response to C. difficile toxins in C.difficile infection (CDI) is incompletely characterized in immunocompromised hosts (ICHs). Methods We conducted a prospective study of hospitalized adults with CDI, with and without immunosuppression (hematologic malignancy, active solid tumor, solid organ or stem cell transplant, inflammatory bowel disease, autoimmune disease, congenital or acquired immunodeficiency, asplenia, chronic receipt of high dose steroids, or receipt of immunosuppressing medications within 12 months). Serum and stool antibody concentrations of IgM, IgG and IgA to C. difficile toxins A and B at treatment days 0, 3, and 10-14 were compared. Results 98 subjects (47 ICH; 51 non-ICH) were enrolled. Baseline serum anti-toxin A and B antibody levels were similar. At day 3, ICHs demonstrated lower serum levels of anti-toxin A IgG, anti-toxin A IgA, and anti-toxin B IgA (all P<0.05). At day 10-14, lower anti-toxin A IgG concentrations were observed in ICHs (ICH: 21 ELISA units [IQR, 16.4-44.6]) compared with non-ICH subjects (49.0 ELISA units [IQR, 21.5-103]); P=0.045). In stool, we observed lower concentrations of anti-toxin B IgA antibodies at baseline and at day 3 for ICH subjects, with a notable difference in concentrations of anti-toxin B IgA at day 3 (ICH: 6.7 ELISA units [IQR, 1.9-13.9] compared with non-ICH: 18.1 ELISA units [IQR, 4.9-31.7]; P=0.003). Conclusions ICHs with CDI demonstrated lower levels of C. difficile anti-toxin antibodies in serum and stool during early CDI therapy compared to non-ICHs. These data provide insight into the humoral response to CDI in ICHs.