B-Cell Responses in Chronic Chagas Disease: Waning of Trypanosoma cruzi–Specific Antibody-Secreting Cells Following Successful Etiological Treatment

Abstract

Abstract Background A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. Methods Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment. Results T. cruzi–specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment. Conclusions T. cruzi–specific antibodies in the circulation of chronically T. cruzi–infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.