Cholinoreceptor autoantibodies in Sjögren sndrome

Previous studies have demonstrated that antibodies against cholinoreceptors of exocrine glands correlate with dry mouth in persons with primary Sjögren 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 PGE₂ production. Our findings indicated that pSS IgG-stimulating M₃, M₄, and M₁ cholinoreceptors exerted an increase in COX-2 mRNA without affecting COX-1 mRNA expression and increased PGE₂ production. Inhibitors of phospholipase A₂, COX-s, L-type calcium channel currents, and Ca²⁺-ATPase from sarcoplasmic reticulum prevented the pSS IgG effect on PGE₂ production. An ionophore of calcium mimicked pSS IgG action, suggesting a crucial role of calcium homeostasis in the cholinoreceptor-stimulated increase in PGE₂ production. Moreover, the amounts of PGE₂ in saliva and in sera from persons with pSS were significantly higher than in pre- or post-menopausal women. These findings illustrate the importance of autoantibodies to cholinoreceptors in the generation of chronic inflammation of target tissues in SS.