The serological antibody repertoire in Chagas Disease

RICCI A; BRACCO L; RAMSEY J; NOLAN M; TORRICO F; ALTCHEH J; KESPER JR N; VILLAR JC; AGÜERO F

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias SAIC . SAFE . SAB . SAP . AACyTAL . NANOMED-ar . HCS; 2019

SAIC . SAFE . SAB . SAP . AACyTAL . NANOMED-ar . HCS

During an infection the immune system produces antibodies against pathogens. With time, the immune repertoires of infected individuals become specific to the history of infections and thus represent a rich source of diagnostic markers. A comprehensive description of the specificities of global antibody repertoires has been hindered by the lack of powerful tools. In Chagas Disease the immune response is directed to Trypanosoma cruzi, a protozoan parasite that evades immune mediated elimination and mounts long-lasting chronic infections. Although available diagnostic tests give satisfactory results in most cases, there is currently no gold standard for diagnosis of infection and discordant results remain a possible cause of undetected cases. Here, using state of the art high-density peptide arrays we examined the global human antibody repertoire developed by Chagas Disease patients. Peptide arrays displaying 2.8 million unique peptides from the complete proteomes of T. cruzi strains CL-Brener (DTU TcVI, 19,668 proteins) and Sylvio X10 (DTU TcI, 10,832 proteins) were assayed with 72 serum samples from infected subjects from Argentina, Bolivia, Brazil, Colombia, Mexico and the US, as well as negative samples from the same regions. A cascading screening strategy was designed to identify the antigenic core of these genomes using pooled samples, and in a secondary screening assay individual serum samples to study seroprevalence of identified antigens and fine map all epitopes. Our analysis uncovered >4,500 antigens and >22,000 antibody-binding regions, delineating both public (shared) Chagas antigens as well as private (non-shared) individual anti-T. cruzi responses. To our knowledge, this the first and largest collection of Chagas Disease antigens and epitopes described to date. This dataset will enable the study of the human antibody repertoire in Chagas Disease at an unprecedented depth and granularity, while also providing a rich dataset of serological biomarkers.