Overview of molecular mechanisms in chagasic cardioneuromyopathy and achalasia

Evidence accumulated by our investigations over the years give adequate pro of 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, tri ggers in the cells intracellular signal transductions that alter the physio logical behaviour of the target organs. These events convert the normal cel ls into pathologically active cells. The interaction of antibodies with hea rt beta adrenergic and cholinergic receptors triggers physiologic, morpholo gic, enzymatic and molecular alterations, leading to tissue damage. The ana lysis of the prevalence and distribution of these antibodies reveals a stro ng association with cardiac and esophageal autonomic dysfunction in seropos itive 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 dis ease, in which the sympathetic and parasympathetic systems are affected. Th e deposit of autoantibodies behaving like an agonist on neurotransmitter re ceptors, induceds desensitization and/or down regulation of the receptors. This in turn, could lead to a progressive blockade of neurotransmitter rece ptors, with sympathetic and parasympathetic dennervation, a phenomenon that has been described during the course of Chagas cardioneuropathy and achala sia. The clinical relevance of these findings is the demonstration, using b iomolecules, of a strong association between the existence of circulating a utoantibodies against peptides corresponding to the second extracellular lo op of the human heart beta, adrenoceptor and M-2 cholinoceptor in chagasic patients, and the presence of dysautonomic symptoms, making these autoantib odies a proper early marker of heart and digestive autonomic dysfunction.