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Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked by Trypanosoma cruzi antigens

^a Instituto de Biofisica Carlos Chagas Filho, CCS, UFRJ, Brazil
^b Hospital Universitário Clementino Fraga Filho, CCS, UFRJ, Rio de Janeiro, RJ, Brazil
^c Instituto de Investigaciones en Ingenieria Genética y Biología Molecular (INGEBI), 1428 Buenos Aires, Argentina
^d Laboratoire d'Enzymologie et de Chimie de Protéins, Centre National de la Recherche Scientifique, F-37032 Tours, France

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 P2ß. 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.—Masuda, M. O., Levin, M., Farias de Oliveira, S., dos Santos Costa, P. C., Bergami, P. L., dos Santos Almeida, N. A., Pedrosa, R. C., Ferrari, I., Hoebeke, J., Campos de Carvalho, A. C. Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked by Trypanosoma cruzi antigens. FASEB J. 12, 1551–1558 (1998)

Key Words: immunoglobulin • heart block • ribosomal P proteins • muscarinic receptor

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