DIFFERENTIAL SCREENING OF TRYPANOSOMA CRUZI ANTIGENS

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Chagas disease is a potentially fatal disease caused by the kinetoplastid protzoan Trypanosoma cruzi. This organism is endemic in most Latin American countries where 16-18 million people are infected, and it constitutes a threat to the blood supply not only in those countries but also in the United States. The majority of chronically infected person are asymptomatic and remain for life in the so-called indeterminate phase of the disease. In 10-30 percent of infected individuals, however, cardiac and gastrointestinal manifestations typical of chronic Chagas disease occur. The study of T. cruzi antigens proposed in this application has three long-term objectives: (1.) to understand the immune processes involved in pathogenesis, (2.) to improve serological methods for diagnosis and (3.) to identify potential candidates for vaccine development. We propose to evaluate recombinant T. cruzi antigens for the humoral and cellular immune responses they elicit in two groups of chronically infected chagasic patients: asymptomatic persons and patients with chagasic cardiomyopathy. These patients have been studied in the Transplantation Immunology Laboratory of the Sao Paulo University Hospital since 1990. By immunoscreening an amastigote cDNA library with these sera, we plan to identify antigens that are recognized by the immune responses of the two groups of patients. Each recombinant antigen will be tested for its reactivity with sera and peripheral blood monocytes (PMBCs) derived from each patient. We hypothesize that two classes of antigens will be found: (a) potentially protective antigens that stimulate B- and/or T cell responses controlling the parasitic infection, responses expected to be more prevalent in asymptomatic patients, and (b) cross-reactive antigens containing epitopes shared by the parasite and mammalian cells that will be more likely identified using sera from cardiac patients with possible autoimmune reactions. Our studies will verify whether there is a correlation between the antibody and/or cellular response to a number of purified parasite antigens and the course of the T. cruzi infection.