Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjogren's syndrome

Objective. Sjogren'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 neurotransmi ssion may contribute to the glandular dysfunction, In this study, we used a functional assay to investigate autoantibody-mediated effects on parasympa thetic neurotransmission and smooth muscle contraction. Methods. Serum and purified IgG were obtained from patients with primary an d secondary SS and from control subjects. Contraction of isolated bladder s trips in response to stimulation of M-3-muscarinic receptors by a muscarini c receptor agonist, carbachol, or by endogenous acetylcholine released from postganglionic parasympathetic nerves was measured before and after the ad dition 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 simila r to 50%, Sera from these patients also inhibited the action of neuronally released acetylcholine at M-3-muscarinic receptors, Sera from 7 of 8 health y individuals, from patients with rheumatoid arthritis without sicca sympto ms, 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 a ssociated with the presence of bladder symptoms and other autonomic feature s. Conclusion. Autoantibodies that act as antagonists at M-3-muscarinic recept ors on smooth muscle occur in a subset of patients with primary and seconda ry SS, Their presence in secondary SS was unexpected and provides new evide nce for a common pathogenetic link between primary and secondary SS, These autoantibodies appear to contribute to sicca symptoms and may explain assoc iated features of autonomic dysfunction in some patients.