Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjögren's syndrome.
OBJECTIVE
Sjögren's syndrome (SS) is an autoimmune disorder characterized by dry eyes and mouth (sicca syndrome) and lymphocytic infiltration of the lacrimal and salivary glands. Abnormalities of parasympathetic neurotransmission may contribute to the glandular dysfunction. In this study, we used a functional assay to investigate autoantibody-mediated effects on parasympathetic neurotransmission and smooth muscle contraction.


METHODS
Serum and purified IgG were obtained from patients with primary and secondary SS and from control subjects. Contraction of isolated bladder strips in response to stimulation of M3-muscarinic receptors by a muscarinic receptor agonist, carbachol, or by endogenous acetylcholine released from postganglionic parasympathetic nerves was measured before and after the addition of patient serum or IgG.


RESULTS
Sera from 5 of 9 patients with primary SS and from 6 of 6 patients with secondary SS inhibited carbachol-evoked bladder contraction by approximately 50%. Sera from these patients also inhibited the action of neuronally released acetylcholine at M3-muscarinic receptors. Sera from 7 of 8 healthy individuals, from patients with rheumatoid arthritis without sicca symptoms, and from patients with systemic lupus erythematosus had no effect. The anti-muscarinic receptor activity was localized in the IgG fraction, since purified IgG from patients with SS also inhibited agonist- and nerve-evoked contractions. In this preliminary study, the autoantibodies seemed to be associated with the presence of bladder symptoms and other autonomic features.


CONCLUSIONS
Autoantibodies that act as antagonists at M3-muscarinic receptors on smooth muscle occur in a subset of patients with primary and secondary SS. Their presence in secondary SS was unexpected and provides new evidence for a common pathogenetic link between primary and secondary SS. These autoantibodies appear to contribute to sicca symptoms and may explain associated features of autonomic dysfunction in some patients.
Waterman
S A
SA
Department of Physiology, University of Adelaide, South Australia, Australia.
Gordon
T P
TP
Rischmueller
M
M
D000109:Acetylcholine / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000276:immunology*; D001743:Urinary Bladder / Q000187:drug effects
D001323:Autoantibodies; D007074:Immunoglobulin G; D018721:Muscarinic Agonists; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D002217:Carbachol; D000109:Acetylcholine