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

CESAR, G; NATALE, M A; ALBAREDA, M C; ALVAREZ, M G; LOCOCO, B; DE RISSIO, A M; FERNANDEZ, M; CASTRO EIRO, M D; BERTOCCHI, G; WHITE, B E; ZABALETA, F; VIOTTI, R; TARLETON, R L; LAUCELLA, S A

JOURNAL OF INFECTIOUS DISEASES

UNIV CHICAGO PRESS

Año: 2022

0022-1899

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.