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

Cesar, G;Natale, MA;Albareda, MC;Alvarez, MG;Lococo, B;De Rissio, AM;Fernandez, M;Castro Eiro, M;Bertocchi, G;White, BE;Zabaleta, F;Viotti, R;Tarleton, RL;Laucella, SA;

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.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.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.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.