Muscarinic acetylcholine receptor antibodies as a new marker of dry eye Sjogren syndrome

PURPOSE. The authors investigated whether circulating autoantibodies agains t M-3 muscarinic acetylcholine receptors (mAChRs) could be a new marker for diagnosis for primary and secondary Sjogren 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 antig ens was used to determine autoantibodies against acinar cells and M-3 mAChR s. Also, nitric oxide synthase (NOS) activity was assessed to determine the biological effect of these autoantibodies in relation to the M-3 mAChR. RESULTS. Sera from dry eye primary SS (pSS) or secondary SS (sSS) patients tested by ELISA recognized membrane lacrimal gland acinar cells antigens an d the synthetic 25-mer peptide, corresponding to the second extracellular l oop of human M-3 mAChRs. Moreover, the IgG fraction and the corresponding a ffinity-purified anti-M-3 peptide autoantibodies from the same patients wer e able to activate NOS coupled to lacrimal gland M-3 mAChRs. AS controls, I gG and sera from women without dry eye with or without rheumatoid arthritis and from normal control subjects gave negative results on ELISA and biolog ical assay; thus demonstrating the specificity of the reaction. CONCLUSIONS. Autoantibodies against mAChR map be considered among the serum factors implicated in the pathophysiology of the development of pSS dry ey es and could be a new marker to differentiate SS dry eyes from non-SS dry e yes.