Anti-M3 Muscarinic Cholinergic Autoantibodies from Patients with Primary Sjögren’s Syndrome Trigger Production of MMP-3 and PGE2 from the Submandibular Glands

Keywords: Autoantibodies, anti-M3 peptide IgG, Sjögrens Syndrome,         
Background: We demonstrated that serum IgG from patients with primary Sjögren’s syndrome (pSS) interacting with the second extracellular loop of human glandular M3 muscarinic acetylcholine receptors (M3 mAChR) trigger the production of MMP-3 and PGE2. Methods: ELISA assays was performed in the presence of M3 mAChR synthetic peptide as antigen to detected in serum the autoantibodies. Also, MMP-3 and PGE2 production in the presence of anti-M3 mAChR autoantibodies were determined. Results: An association between serum and anti-M3 mAChR autoantibodies and serum levels of MMP-3 and PGE2 in pSS patients was observed. Thus, we established that serum anti-M3 mAChR autoantibodies, MMP-3 and PGE2 may be considered to be early markers of pSS associated with inflammation. Affinity-purified anti-M3 mAChR peptide IgG from pSS patients, while stimulating salivary-gland M3 mAChR, causes an increase in the level of MMP-3 and PGE2 as a result of the activation of  PLA2 and COX-2 (but not COX-1). Conclusions: These results provide a novel insight into the part that cholinoceptor antibodies play in the development of glandular inflammation. This is the first report showing that an antibody interacting with glandular mAChR can induce the production of proinflammatory mediators (MMP-3/PGE2).