Investigating serodiscordance and borderline serology in Chagas Disease using high-density peptide arrays.

JANINE RAMSEY ; MENDICINO, DIEGO; LUZ RODELES; IVÁN MARCIPAR; LEONEL BRACCO; LUZ PEVERENGO; FERNÁN AGÜERO

Mar del Plata

Congreso; Investigating serodiscordance and borderline serology in Chagas Disease using high-density peptide arrays; 2019

Diagnosis of chronic Chagas Disease is currently based on serological techniques. Although available diagnostic tests give satisfactory results in most cases, there is currently no gold standard 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 of chronic Chagas Disease patients as well as serodiscordant and borderline serology cases. First, 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 serum samples from infected subjects from Argentina, Bolivia, Brazil, Colombia, Mexico and the US, as well as negative samples from the same regions. This allowed us to identify the antigenic subset of T. cruzi peptides recognized by a diverse collection of sera. Next, in a second screening focusing on 400,000 pepdies selected from this subset we assayed individual serum to study 28 serodiscordant cases from Argentina and Mexico with borderline serology. These displayed a wide reactivity based on the number of positive peptides and quantification of signal. We observed almost complete lack of correlation between the quantitative values obtained in commercial ELISA (Wiener v4.0) and those obtained by the array. Hence, there is much room for improvement of current serological diagnosis. Based on the reactivity against 6 known antigens, we have separated these sera in three groups: one group of 17 sera reactive against several antigens; a second group of 8 sera reactive with fewer antigens and a group of 3 sera that were negative against most known antigens assayed. Using this information we will shortlist novel antigens from the high-content screening to improve existing diagnostic kits. In this presentation we will revisit the concept of serodiscordance in the light of all new data arising from this screen.