Functional implications of circulating muscarinic cholinergic receptor autoantibodies in chagasic patients with achalasia

Background & Aims: Autoantibodies against M-2-muscarinic acetylcholine rece ptors (M-2 mAChR) have been reported in patients with chronic Chagas' disea se who have cardiac dysautonomia. The aim of this study was to investigate the presence of such antibodies in chronic chagasic and non-chagasic patien ts with esophageal achalasia and their ability to activate M-2 mAChR in the isolated esophagus. Methods: Enzyme-linked immunosorbent assay was used to detect serum immunoglobulin (Ig) G antibodies against a synthetic 24-mer p eptide corresponding to the second extracellular loop of human M-2 mAChR, T he effects of both total serum IgG and affinity-purified antipeptide antibo dies on the contractile activity and adenosine 3',5'-cyclic monophosphate ( cAMP) production in rat esophageal strips were also tested. Results: Circul ating IgG antibodies from chagasic achalasia patients recognized the M-2-pe ptide more often than those from non-chagasic achalasia patients (P < 0.000 5) and normal subjects (P < 0.0001), A strong association between the exist ence of circulating anti-M-2 mAChR antibodies and the presence of achalasia in chagasic patients was found (P < 0.01). Both the total IgG fraction and anti-M-2-peptide antibodies increased the basal tone, reduced the relaxant effect of isoproterenol, and decreased cAMP accumulation in esophageal str ips, displaying a muscarinic agonist-like activity on M-2, mAChR. Conclusio ns: Patients with chronic Chagas' disease have circulating autoantibodies a gainst M-2 mAChR, These antibodies could be involved in the pathophysiologi cal mechanism of chagasic achalasia.