Open Forum Infectious Diseases | June 1, 2021

Alonso CD, Papamichael K, Sprague R, Barrett C, Gonzales-Luna AJ, Daugherty K, Garey KW, Villafuerte-Gálvez J, Xu H, Lin Q, Wang L, Chen X, Pollock NR and Kelly CP

Open forum infectious diseases. 2021

DOI: https://doi.org/10.1093/ofid/ofab286

This study was performed using a Simoa Homebrew assay.

Abstract

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.