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Construction of Trypanosoma Cruzi epitope phage display library to identify antibody profile in chronic chagas cardiomyopathy

Grant number: 19/11821-1
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): August 01, 2019
Effective date (End): July 31, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Alexandre da Costa Pereira
Grantee:Gabriela Venturini da Silva
Supervisor abroad: Cristine E. Seidman
Home Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Local de pesquisa : Harvard University, Boston, United States  
Associated to the scholarship:17/13706-0 - Comprehensive T. cruzi and auto-antibody profiling in Chagas cardiomyopathy: leveraging phage-display and next-generation sequencing to reassess an old hypothesis, BP.PD

Abstract

Heart Failure (HF) is worldwide epidemic problem and is the result from multiple underlying cardiovascular and systemic conditions. Chronic Chagas Cardiomyopathy (CCC) is one of the HF caused by infectious process. Chagas Disease is a tropical disease caused by intracellular parasite Trypanosoma cruzi (T cruzi) and, despite the high prevalence in Latin America countries, the number of infected people in non-endemic areas such as United States and Canada is raising in last decades. Currently, around 8 million people are infected with T cruzi and approximately 70 million are at risk of infection. Around 70% of infected people still in an asymptomatic form; however, decades after the infection, 30% will develop some chronic manifestation and, among them, CCC is the most severe manifestation. Until the moment, there is no cure for chronic form of the disease or any biomarker or clinical feature can be useful as a predictor of CCC development. The mechanisms involved in the CCC development are not well stablish, but the immune response has been highlighted since 90s as a mediator of disease pathogenicity. Both, a specific response against the parasite and host autoimmune response, seem to have a role in chronic response after the infection and implicate in disease development. Here we are proposing to use a high-throughput methodology that is able to comprehensively screen antibody response in biological samples for the entire range of Tcruzi proteome. Using PhIPseq methodology, we will profile sera from Chagas patients with and without cardiomyopathy to identify T. cruzi epitopes and associate presence and titers of identified antibodies to disease severity and progression. For this, we will construct a specific library carrying T cruzi peptides and screen them using a large collection of blood samples organized by the Brazilian Consortium for Genetics of Chagas Cardiomyopathy.