Overview of molecular mechanisms in chagasic cardioneuromyopathy and achalasia.
Evidence accumulated by our investigations over the years give adequate proof for the existence of circulating antibodies in Chagas disease which bind to beta adrenergic and muscarinic cholinergic receptor of myocardium. The interaction of agonist-like antibodies with neurotransmitter receptors, triggers in the cells intracellular signal transductions that alter the physiological behaviour of the target organs. These events convert the normal cells into pathologically active cells. The interaction of antibodies with heart beta adrenergic and cholinergic receptors triggers physiologic, morphologic, enzymatic and molecular alterations, leading to tissue damage. The analysis of the prevalence and distribution of these antibodies reveals a strong association with cardiac and esophageal autonomic dysfunction in seropositive patients in comparison with those without alteration of the heart and esophagus autonomic disorders: therefore, the presence of these antibodies may partially explain the cardiomyoneurophathy and achalasia of Chagas disease, in which the sympathetic and parasympathetic systems are affected. The deposit of autoantibodies behaving like an agonist on neurotransmitter receptors, induceds desensitization and/or down regulation of the receptors. This in turn, could lead to a progressive blockade of neurotransmitter receptors, with sympathetic and parasympathetic dennervation, a phenomenon that has been described during the course of Chagas cardioneuropathy and achalasia. The clinical relevance of these findings is the demonstration, using biomolecules, of a strong association between the existence of circulating autoantibodies against peptides corresponding to the second extracellular loop of the human heart beta, adrenoceptor and M2 cholinoceptor in chagasic patients, and the presence of dysautonomic symptoms, making these autoantibodies a proper early marker of heart and digestive autonomic dysfunction.
Sterin-Borda
L
L
CEFYBO-CONICET, Facultad de Medicina y Odontología, Universidad de Buenos Aires, Argentina. leo@cefybo.edu.ar
Borda
E
E
D000913:Antibodies, Protozoan / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000378:metabolism*; D002598:Chagas Cardiomyopathy / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D004931:Esophageal Achalasia / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D009468:Neuromuscular Diseases / Q000276:immunology* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism
D000913:Antibodies, Protozoan; D001323:Autoantibodies; D007074:Immunoglobulin G; D011943:Receptors, Adrenergic, beta; D011950:Receptors, Cholinergic; D017981:Receptors, Neurotransmitter