Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked byTrypanosoma cruziantigens

Abstract

Antibodies of chronic chagasic patients have been shown to interfere with electric and mechanical activities of cardiac embryonic myocytes in culture and with whole mammalian hearts. A mechanism proposed for this effect involves interaction of the antibodies with G-protein-linked membrane receptors, thus leading to activation of beta adrenergic and muscarinic receptors; more specifically, IgG of chagasic patients would interact with the negatively charged regions of the second extracellular loop of these receptors. We performed competition experiments to test this hypothesis. We evaluated the effect of sera/IgG from patients previously known to depress electrogenesis and/or atrioventricular conduction in isolated rabbit hearts after incubation with live and lysed parasites, the peptide corresponding to the second extracellular loop (O2) of the M2 receptor, and different peptides derived from two ribosomal proteins of T. cruzi: P0 and P2beta. Our results indicate that 1) the antigenic factor inducing the functionally active IgGs in the chagasic patients is probably an intracellular T. cruzi antigen; 2) IgG/serum is interacting with the O2 region of the M2 receptor in the rabbit heart; and 3) the negative charges present in the ribosomal proteins of T. cruzi are important in mediating the interaction between the patients' serum/IgG and the receptor.

Sera from chronic chagasic patients depress cardiac electrogenesis and conduction

“…We further demonstrated that the depressing effects of the sera on cardiac electrogenesis were me-P.C.S. Costa et al diated by the activation of muscarinic receptors by their IgG fraction (2,3). We now report results obtained from experiments with sera from 58 CCh patients that were screened for the presence of muscarinic activity, as well as beta-adrenergic activity as previously reported for other preparations by Borda and collaborators (4,5).…”

Agonistic AT1 Receptor Autoantibody Increases in Serum of Patients with Refractory Hypertension and Improves Ca2+ Mobilization in Cultured Rat Vascular Smooth Muscle Cells

“…Because we also observed 3 of 37 normotensives had positive response in ELISA and some BP well-controlled patients always maintained positive antibodies in circulation. And there was little evidence to support molecular mimicry theory to explain the AT 1 receptor autoantibody phenomenon, which could well explain the antibodies directed against other G-protein receptors in Chagas' disease or in myasthenia gravis (31,32). There were several speculations on the origin of AT 1 -AAs in previous works.…”

Humoral Immune Response against P2β from Trypanosoma cruzi in Persons with Chronic Chagas Disease: Its Relationship with Treatment Against Parasites and Myocardial Damage

“…13,14 Furthermore, antibodies against P2β are known to cause electrocardiographic alterations in non-infected hearts of immunized mice, which suggests possible involvement of these antibodies in experimental chagasic cardiomyopathy. 15,16 The immune response elicited by the parasite may be also modified by specific chemotherapy because interferon-γ-producing T cells specific for T. cruzi decreased after 12 months of treatment to become unnoticeable in many treated patients. 17 Unlike cross-sectional studies in which predictors and outcome variables are measured on one occasion, longitudinal studies offer the opportunity of repeated measures to provide a better scenario for the study of relationships between personal characteristics or exposures and occurrence of healthrelated events.…”