Functional implications of circulating muscarinic cholinergic receptor autoantibodies in chagasic patients with achalasia.
OBJECTIVE
Autoantibodies against M(2)-muscarinic acetylcholine receptors (M(2) mAChR) have been reported in patients with chronic Chagas' disease who have cardiac dysautonomia. The aim of this study was to investigate the presence of such antibodies in chronic chagasic and non-chagasic patients 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 peptide corresponding to the second extracellular loop of human M(2) mAChR. The effects of both total serum IgG and affinity-purified antipeptide antibodies on the contractile activity and adenosine 3', 5'-cyclic monophosphate (cAMP) production in rat esophageal strips were also tested.


RESULTS
Circulating IgG antibodies from chagasic achalasia patients recognized the M(2)-peptide more often than those from non-chagasic achalasia patients (P < 0.0005) and normal subjects (P < 0.0001). A strong association between the existence 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 strips, displaying a muscarinic agonist-like activity on M(2) mAChR.


CONCLUSIONS
Patients with chronic Chagas' disease have circulating autoantibodies against M(2) mAChR. These antibodies could be involved in the pathophysiological mechanism of chagasic achalasia.
Goin
J C
JC
Pharmacological Units, School of Dentistry, University of Buenos Aires, Argentina.
Sterin-Borda
L
L
Bilder
C R
CR
Varrica
L M
LM
Iantorno
G
G
Ríos
M C
MC
Borda
E
E
D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000494:pharmacology; D014355:Chagas Disease / Q000097:blood / Q000150:complications* / Q000276:immunology*; D000242:Cyclic AMP / Q000378:metabolism; D004931:Esophageal Achalasia / Q000150:complications* / Q000503:physiopathology; D004947:Esophagus / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000276:immunology*
D001323:Autoantibodies; D011976:Receptors, Muscarinic; D000242:Cyclic AMP