Pathogenesis of human chronic chagasic myocarditis.

Studies carried out during the last decades provided evidence in support of an autoimmune pathogenesis for chronic chagasic myocarditis. This opinion was based on 1) the demonstration of molecular mimicry between parasite and host antigens, 2) the appearance of autoantibodies recognizing heart epito pes during the chronic phase of infection, 3) the induction of myocarditis and electrocardiographic alterations in animals immunized with whole parasi tes, parasite fragments or with biochemically-defined antigens, 4) the isol ation from the heart of inflammatory infiltrates of B cells elaborating ant ibodies against myocardial antigens and 5) or of T cell clones reacting wit h heart epitopes and 6) induction of heart and nervous tissue alterations b y transfer of lymphocytes from infected animals into naive syngeneic hosts. However, the characteristics of the inflammatory infiltrate in human myoca rditis, displaying a wide variety of cells, many of them not involved in au toreactivity, such as the presence of giant cell granulomas and abundant eo sinophils, as well as its focality and asynchrony, and the frequent associa tion with pericarditis, casts doubts about the possibility of autoimmunity being responsible for the perpetuation of the myocarditis. This is supporte d by the recent observation that treatment of asymptomatic patients with tr ypanocidal drugs prevents the development of cardiopathy and that parasite components, either antigens or genomic fragments, are present at the site o f the inflammatory lesions. On the basis of this new evidence, other altern ative pathogenetic mechanisms should be sought to explain the appearance of a polymorphic long-lasting myocarditis that needs the presence of tiny fra gments of parasites to develop. in addition to the well known immunological pathogenesis, the link between such a small amount of parasite components, below the level of microscopic detection, and the induction of such an ext ensive inflammatory infiltrate, represents interesting avenues for research in the near future.