AUTOIMMUNITY IN CHAGAS-DISEASE CARDIOPATHY - BIOLOGICAL RELEVANCE OF A CARDIAC MYOSIN-SPECIFIC EPITOPE CROSS-REACTIVE TO AN IMMUNODOMINANT TRYPANOSOMA-CRUZI ANTIGEN

Heart tissue destruction in chronic Chagas disease cardiopathy (CCC) m ay be caused by autoimmune recognition of heart tissue by a mononuclea r cell infiltrate decades after Trypanosoma cruzi infection. Indirect evidence suggests that there is antigenic crossreactivity between T. c ruzi and heart tissue. As there is evidence for immune recognition of cardiac myosin in CCC, we searched for a putative myosin-crossreactive T. cruzi antigen. T. cruzi lysate immunoblots were probed with anti-c ardiac myosin heavy chain. IgG antibodies (AMA) affinity-purified from CCC or asymptomatic Chagas disease patient-seropositive sera. A 140/1 16-kDa doublet was predominantly recognized by AMA from CCC sera. Furt her, recombinant T. cruzi protein B13-whose native protein is also a 1 40- and 116-kDa double band-was identified by crossreactive AMA. Among 28 sera tested in a dot-blot assay, AMA from 100% of CCC sera but onl y 14% of the asymptomatic Chagas disease sera recognized B13 protein ( P = 2.3 x 10(-6)). Sequence homology to B13 protein was found at posit ions 8-13 and 1442-1447 of human cardiac myosin heavy chain. Competiti ve ELISA assays that used the correspondent myosin synthetic peptides to inhibit serum antibody binding to B13 protein identified the heart- specific AAALDK (1442-1447) sequence of human cardiac myosin heavy cha in and the homologous AAAGDK B13 sequence as the respective crossreact ive epitopes. The recognition of a heart-specific T. cruzi crossreacti ve epitope, in strong association with the presence of chronic heart l esions, suggests the involvement of crossreactivity between cardiac my osin and B13 in the pathogenesis of CCC.