Exploring clinical serological correlations at large scale: changes in the antibody repertoire of patients with Chagas Disease Cardiomyopathy

PRINCIPATO M; VON WULFFEN A; AGÜERO F; RICCI A; PAOLUCCI A; BRACCO L; CARBAJALES J; CIAMPI N; JUAN MUCCI,

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 their clinical history and thus represent a rich source of diagnostic markers. How these serological markers correlate with pathology is an open question. Chagas Disease (CD) is caused by the protozoan parasite Trypanosoma cruzi and develops into Chagas Disease Cardiomyopathy (CCD) in ~30% of cases. CCD can be mild (stage B1) or evolve to cause arrhythmias and bundle branch blocks (stage B2) progressing to dilation (stages C, D) which can result in further symptoms and complications leading to mortality. In this work we investigated serological correlations in 17 individuals at different stages of CCD. Using high-density arrays displaying 2.8 million peptides from the complete proteomes of two T. cruzi strains (CL-Brener + Sylvio X10) we examined antibody repertoires using pooled samples from three groups of CCD patients: stage B1, stage B2, and stages C+D. These pools, were used to map reactive antigens in these patients and search for epitope markers that could correlate with disease progression. Next, using a subset of ~400,000 peptides, we assayed serum samples from a 42 year old patient that showed progression of CCD. At age 39 the heart ejection fraction (EF) was 52% accompanied by electrocardiogram with synus rythm, right bundle block and left anterior hemiblock (Sample1). One year later EF worsened to 39% accompanied by complex ventricular arrhythmia (Sample2), maintaining similar values until today. Analysis of these two serum samples showed ~320 T. cruzi antigens with significant serological changes between both stages (threshold = 50% signal change). Similar fractions of antigens increased or decreased measured antibody levels. To our knowledge, this is the first and largest collection of Chagas Disease antigens and epitopes correlated with pathology, providing a rich source of serological biomarkers.