Determination of the humoral antigenic profile from chagasic patients using Trypanosoma cruzi genome shotgun phage display

Abstract

Chagas' disease is a chronic illness and an important health issue in Brazil, Latin America and, more recently, in the world due to the steady increase in migration to developed countries. It is estimated that 200,000 people will die due to Chagas' disease in the next five years. Since there is no vaccine and existing therapies rely mostly on old drugs with limited efficacy and toxic side effects, it is crucial to develop novel therapeutic and diagnostic alternatives for the disease. Cardiomyopathy is the main cause of death, which develops in about a third of infected individuals. The reason why the other two thirds remain asymptomatic is still unclear. Due to the apparent lack of parasites in the heart and the presence of auto-antibodies in the sera, it has been proposed that Chagas' disease could be an autoimmune disease. However, using more advanced techniques, it has been shown that these patients still have extremely low number of parasites in their heart, which lead to inflammatory reactions that contribute to disease progression. However, the molecular mechanisms of disease progression are not yet fully understood. To help understanding the importance of the immune system in Chagas' disease, in particular the humoral response, we will explore the immune repertoire of T. cruzi using combinatorial biology. Genome shotgun libraries will be utilized to map the humoral response of T. cruzi infected patients throughout the different stages of the disease. Our expectation is that this work will lead to the identification and validation of novel T. cruzi antigens, which might contribute to the development of novel diagnostic and therapeutic options for Chagas' disease patients. (AU)