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Anti-Trypanosoma cruzi Antibody Isotype Profiles in Patients with Different Clinical Manifestations of Chagas' Disease

Chagas' disease results from infection with the protozoan hemoflagellate Trypanosoma cruzi. Patients in the chronic phase of infection can be categorized into four groups based on the presence of cardiac abnormalities (CARD), gastrointestinal involvement (DIGEST), a combination of both presentations (BOTH), or indeterminate (IND) if Chagas' related pathology is not apparent. Previous studies have indicated that parasite-specific antibody production is important in both resistance to and pathogenesis of disease. The anti-T. cruzi epimastigote stage antibody isotype profiles in the sera of Brazilian patients from each clinical category, as well as from uninfected individuals (UNINF) from the same endemic area were analyzed. Anti-epimastigote immunoglobulin G (IgG)1 and IgG3 levels were strikingly high with titers 1:100,000. Sera from patients in the CARD group had higher levels of IgM than either UNINF or IND individuals, which is consistent with the theory that autoimmunity may contribute to chagasic cardiomyopathy. The IgA levels were higher in sera from patients with gastrointestinal involvement when compared with individuals from any of the other clinical categories as well as from uninfected controls. Interestingly, patients with both digestive and cardiac involvement did not express high serum levels of IgA. However, like patients with cardiac involvement alone, persons with both clinical manifestations produced elevated levels of IgG2 compared with the IND or UNINF groups. These data suggest the presence of complex immunoregulatory processes, most likely related to differential cytokine involvement, which can influence the expression of antibody isotypes and possibly the course of disease.