Induction of antibodies reactive to cardiac myosin and development of heart alterations in cruzipain-immunized mice and their offspring

Human and murine infection with Trpanosoma cruzi parasite is usually accomp anied by strong humoral and cellular immune response to cruzipain, a parasi te immunodominant antigen. In the present study we report that the immuniza tion of mice with cruzipain devoid of enzymatic activity, was able to induc e antibodies which bind to a 223-kDa antigen from a mouse heart extract. We identified this protein as the mouse cardiac myosin heavy chain by sequenc ing analysis. The study of IgG isotype profile revealed the occurrence of a ll IgG isotypes against cruzipain and myosin. IgG1 showed the strongest rea ctivity against cruzipain, whereas IgG2a was the main isotype against myosi n. Anti-cruzipain antibodies purified by immunoabsorption recognized the ca rdiac myosin heavy chain, suggesting cross-reactive epitopes between cruzip ain and myosin. Autoimmune response in mice immunized with cruzipain was as sociated to heart conduction disturbances. In addition, ultrastructural fin dings revealed severe alterations of cardiomyocytes and IgG deposit on hear t tissue of immunized mice. We investigated whether antibodies induced by c ruzipain transferred from immunized mothers to their offsprings could alter the heart function in the pups. All IgG isotypes against cruzipain derived from transplacental crossing were detected in pups' sera. Electrocardiogra phic studies performed in the offsprings born to immunized mothers revealed conduction abnormalities. These results provide strong evidence for a path ogenic role of autoimmune response induced by a purified T: cruzi antigen i n the development of experimental Chagas' disease.