Autoantibodies against Submandibular Gland Muscarinic Cholinoceptor Subtypes in Primary Sjögren Syndrome

Abstract

Sjögren Syndrome (SS) is a chronic autoimmune disease characterized by parasympathetic exocrine gland dysfunction. Here, the involvement of submandibular gland muscarinic acetylcholine receptor (mAChR) M4 subtype is proposed as an IgG target together with M1 and M3 mAChR subtypes. The Kd values were total membranes 0.20 ± 0.017 nM; acini membranes 0.33 ± 0.023 nM and duct membranes 0.22 ± 0.040 nM and Bmax values were total, 1038 ± 24, acini, 1359 ± 28 and ducts, 593 ± 30. The rank order of Bmax was: acini > total > ducts, indicating that acini express the highest number of binding sites. The specific mAChR antagonists (4-DAMP [M3], tropicamide [M4], pirenzepine [M1]) and the corresponding synthetic peptides impaired IgG-mAChR subtype interactions. The specificity of these reactions was assessed by the corresponding affinity-purified anti peptide antibodies recognizing M4, M3 and M1 mAChR. These data concerning autoantibodies contribute to explain the pathogenesis of SS and also represent a new clinical marker for SS diagnosis.