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.