Chagasic Cardiopathy

Abstract

SUMMARYTwenty-four out of 25 patients with Chagas' heart disease have circulating immunoglobulins which react by indirect immunofluorescence technique with endocardium, interstitium and blood vessels of the heart. With skeletal muscle the reaction was observed in interstitium and vascular structures, but with other organs it was limited to vascular structures. This endocardial-vascularinterstitial factor (EVI) fixed complement. Some evidence indicated that this reaction could be obtained using the serum and tissues from the same patient: for instance, in one positive case a right atrium biopsy was performed. When this substrate was used for indirect immunofluorescence, employing the patient's own serum, positive results were obtained. Specificity is not related to AB blood group systems, or to Forssman or Wassermann antigens. The reacting factor was effectively absorbed from sera with organ homogenates, and with guinea pig red blood cells although it was independent of heterophil antibodies. In almost all cases studied, the EVI factor of the serum, when absorbed with epimastigotes of T.cruzi, results in a negative reaction, suggesting that the genesis of the reacting gamma globulin is related to antigens of T.cruzi.The EVI factor was also observed in 19 of 47 asymptomatic controls from an endemic area with positive serology for T.cruzi and in 3 of 27 with negative serology. These 3 cases had anti-T.cruzi antibodies in titers just below those considered of clinical value. The EVI factor was not observed in 119 normal individuals and 286 patients with selected cardiovascular diseases or another pathology from a nonendemic area. These findings and those mentioned above were statistically significant (P < 0.001). These results indicate the possibility of a more accurate diagnosis of chagasic myocardiopathy based on the study of the EVI factor, because in an individual case the diagnosis of chronic chagasic cardiopathy can be considered with a low probability in the absence of this factor.

Autoimmunity in Chagas disease cardiopathy: biological relevance of a cardiac myosin-specific epitope crossreactive to an immunodominant Trypanosoma cruzi antigen.

“…sensitivity responses toward a tissue-specific heart component bearing structural similarities to a given T. cruzi antigen. Several investigators found autoantibody and self-reactive T-cell formation in human and experimental T cruzi infection (5,6). Crossreactive autoantibodies were mainly directed toward ubiquitous and evolutionarily conserved molecules (7,8).…”

Basement Membrane Peptides: Functional Considerations and Biomedical Applications in Autoimmunity

“…Sera from patients suffering from both forms of the disease demonstrate cross-reactivity with the parasite as well as with normal endocardium, blood vessels, and material surrounding striated muscle and Schwann cells [25]. It was further recognized that these sera as well as sera from primates infected with Trypanosoma cruzi reacted specifically with basement membranes, as can be seen in Fig.…”

Molecular mimicry by Trypanosoma cruzi: the F1-160 epitope that mimics mammalian nerve can be mapped to a 12-amino acid peptide.

“…Autoreactive antibodies and T cells directed to target organs have been described in experimental and natural chronic T. cruzi infection (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). There are at least two nonexclusive explanations for the generation of autoimmunity in Chagas disease: (i) infection with the parasite perturbs immunoregulation, leading to loss of tolerance for self-antigens; (ii) immune recognition of T. cruzi antigens is crossreactive with selected mammalian antigens, leading to autoimmunity (molecular mimicry).…”

“…Antibodies to endocardium, vasculature, and interstitium of striated muscle (EVI) and Schwann cells ofperipheral nerve have been found in acute and chronic cases of Chagas disease (3,4). Antibodies to EVI have been found to be directed to carbohydrate on mammalian laminin, apparently stimulated by crossreactive carbohydrate epitopes present in T. cruzi (5,6).…”