Cholinoreceptor autoantibodies in Sjogren syndrome

Previous studies have demonstrated that antibodies against cholinoreceptors of exocrine glands correlate with dry mouth in persons with primary Sjogren syndrome ( pSS). The aim of the present investigation was to establish if serum IgG antibodies ( pSS IgG) were able to interact with cholinoreceptors in rat submandibular gland-dependent stimulation of cyclo-oxygenase 2 ( COX-2) mRNA expression and PGE(2) production. Our findings indicated that pSS IgG-stimulating M 3, M 4, and M 1 cholinoreceptors exerted an increase in COX-2 mRNA without affecting COX-1 mRNA expression and increased PGE2 production. Inhibitors of phospholipase A (2), COX-s, L-type calcium channel currents, and Ca2+-ATPase from sarcoplasmic reticulum prevented the pSS IgG effect on PGE(2) production. An ionophore of calcium mimicked pSS IgG action, suggesting a crucial role of calcium homeostasis in the cholinoreceptor-stimulated increase in PGE(2) production. Moreover, the amounts of PGE(2) in saliva and in sera from persons with pSS were significantly higher than in pre- or postmenopausal women. These findings illustrate the importance of autoantibodies to cholinoreceptors in the generation of chronic inflammation of target tissues in SS.