B cell responses in chronic Chagas disease: Waning of Trypanosoma cruzi-specific antibody-secreting cells following successful etiological treatment

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B cell responses in chronic Chagas disease: Waning of Trypanosoma cruzi-specific antibody-secreting cells following successful etiological treatment

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 and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric subjects with chronic Chagas disease prior to and after etiological treatment.

Results: Trypanosoma cruzi-specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated subjects with declining parasite-specific antibody levels posttreatment, whereas B cells in most subjects with unaltered antibody levels were low prior to 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 non-infection profile after successful treatment.

Conclusions: T. cruzi-specific antibodies in the circulation of chronically T. cruzi-infected subjects likely derive from both antigen-driven plasmablasts, that disappear following successful treatment, and long-lived plasma cells that persist and account for the low frequency and long course to complete seronegative conversion in successfully treated subjects.

G Cesar, M A Natale, M C Albareda, M G Alvarez, B Lococo, Ana María De Rissio, Marisa Fernandez, M Castro Eiro, G Bertocchi, B E White, F Zabaleta, R Viotti, R L Tarleton, S A Laucella.J Infect Dis. 2022 Dec 26;jiac495. doi: 10.1093/infdis/jiac495. Online ahead of print.