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Role of Neurotransmitter Autoantibodies in the Pathogenesis of Chagasic Peripheral Dysautonomia
Author(s) -
STERINBORDA LEONOR,
BORDA ENRI
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb05393.x
Subject(s) - autoantibody , chagas disease , dysautonomia , medicine , endocrinology , cholinergic , biology , autonomic nervous system , receptor , neurotransmitter , immunology , antibody , heart rate , disease , blood pressure
A bstract : Chagas' disease is caused by a parasite, Trypanosoma cruzi , which is widely distributed in South and Central America. Dysautonomias, derangements of sympathetic and parasympathetic nervous system function, are seen fairly often during the chronic course of Chagas' disease. Many infected subjects developed, in the course of the disease, neurogenic cardiomyopathy or digestive damage. Our investigations show the existence of circulating antibodies in Chagas' disease that bind to β‐adrenergic and muscarinic cholinergic receptor (mAChR). The neurotransmitter receptor‐autoantibody interaction triggers in the cells intracellular signal transductions that alter the physiological behavior of the target organs, leading to tissue damage. Moreover, the deposit of autoantibodies behaving as agonists induces desensitization and/or down regulation of the receptors. This in turn can lead to a progressive blockade of them with sympathetic and parasympathetic denervation. Using synthetic peptides for immunoblotting and enzyme immunoassay, we demonstrated that these autoantibodies reacted against the second extracellular loop of the human heart β 1 adrenoceptor and M 2 cholinoceptor. Also, the corresponding affinity‐purified antipeptide antibodies displayed an agonist‐like activity associated with specific receptor activation. A strong association between circulating antipeptide M 2 mAChR autoantibodies and the presence of patients' low heart rate variablity index, bradycardia and cardiac or esophageal autonomic dysfunction in chronic chagasic patients was verified. This fact make these antipeptide antibodies a proper marker of cardiac neoromyopathy and achalasia.