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From the Pharmacology Unit, School of Dentistry and the Pathology and Pharmacology Department, School of Medicine, Buenos Aires University; and National Research Council (CONICET), Buenos Aires, Argentina.
PURPOSE. The authors investigated whether circulating autoantibodies against M3 muscarinic acetylcholine receptors (mAChRs) could be a new marker for diagnosis for primary and secondary Sjögren syndrome (SS) dry eye.
METHODS. Enzyme-linked immunosorbent assay (ELISA) using both rat exorbital lacrimal gland acinar cell membranes and synthetic 25-mer peptide as antigens was used to determine autoantibodies against acinar cells and M3 mAChRs. Also, nitric oxide synthase (NOS) activity was assessed to determine the biological effect of these autoantibodies in relation to the M3 mAChR.
RESULTS. Sera from dry eye primary SS (pSS) or secondary SS (sSS) patients tested by ELISA recognized membrane lacrimal gland acinar cells antigens and the synthetic 25-mer peptide, corresponding to the second extracellular loop of human M3 mAChRs. Moreover, the IgG fraction and the corresponding affinity-purified anti-M3 peptide autoantibodies from the same patients were able to activate NOS coupled to lacrimal gland M3 mAChRs. As controls, IgG and sera from women without dry eye with or without rheumatoid arthritis and from normal control subjects gave negative results on ELISA and biological assay; thus demonstrating the specificity of the reaction.
CONCLUSIONS. Autoantibodies against mAChR may be considered among the serum factors implicated in the pathophysiology of the development of pSS dry eyes and could be a new marker to differentiate SS dry eyes from non-SS dry eyes.
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