Abstract
Sjogren’s Syndrome (SS) is a systemic autoimmune disease characterized by focal mononuclear cell infiltration into target organs such as salivary and lacrimal glands, leading to sicca symptoms. SS is characterized by the production of numerous circulating autoantibodies. The anti-muscarinic autoantibodies against the type 3 receptor (anti-M3R autoantibodies) in primary SS patients’ sera has recently been studied as its possible involvement in the pathogenesis of SS and a capable diagnostic marker, since M3R plays critical roles in exocrine secretion and smooth muscle contraction. Anti-M3R autoantibodies in the sera of SS patients were detectable with high sensitivity and specificity and had broad inhibitory effects on the exocrine secretion and the smooth muscle contraction mediated by parasympathetic neurons. In Salivary Gland Epithelial Cells (SGECs), the inhibitory effect of SS autoantibodies on M3R function were verified at the cellular and molecular levels; anti-M3R autoantibodies inhibited carbachol-induced [Ca2+]i increase and the activities of ion channels and membrane transporters, that are dependent on [Ca2+]i. Anti-M3R autoantibodies appear to inhibit M3R function in two ways: acute desensitization of M3R by direct occupation of agonist binding sites of the receptor and the resulting receptor internalization. Abundant anti-M3R autoantibodies may bind to the remaining unoccupied M3Rs, thereby causing progressive and long-term loss of M3R function. Anti-M3R positivity in SS patients was also associated with some clinical manifestations such as leucopenia, anemia, and thrombocytopenia. In this review, we will discuss the prevalence of anti-M3R autoantibodies in the sera of SS patients, the inhibitory effect of anti-M3R autoantibodies in various tissues, and the potential role of anti-M3R autoantibodies with SGECs in the pathogenesis of SS.
Highlights
Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands, leading to xerostomia and xerophthalmia
SS can be divided into primary SS and secondary SS, in which the sicca symptoms are associated with other autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis [1,2]
Lee et al [34] further confirmed that aquaporin 5 (AQP5) trafficking to the plasma membrane was inhibited by antiM3R autoantibodies in SS. These findings strongly suggest that antiM3R autoantibodies have multifaceted effects, possibly through direct binding of anti-M3R autoantibodies to M3R and by affecting other molecules involved in salivary secretion
Summary
Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands, leading to xerostomia and xerophthalmia. SS has diverse extraglandular organ involvement including in the gastrointestinal tract, lung, renal, bladder, blood vessels, and peripheral and central nervous system. SS can be divided into primary SS (pSS) and secondary SS, in which the sicca symptoms are associated with other autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis [1,2]. Patients with SS have inflammatory lesions in their target organs characterized by lymphocytic infiltration at the focal, periductal and perivenular sites with abnormal T and B cell activity. The proportion of the infiltrating mononuclear cells is associated with the severity of the autoimmune lesion [3]
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