AUTOANTIBODIES AGAINST LACRIMAL GLAND M-3 MUSCARINIC ACETYLCHOLINE-RECEPTORS IN PATIENTS WITH PRIMARY SJOGRENS-SYNDROME

PURPOSE. The authors demonstrated that immunoglobulin G, present in th e sera of patients with primary Sjogren syndrome (pSS), could recogniz e and activate muscarinic acetylcholine receptors (mAChRs) of rat exor bital acrimal gland. METHODS. Sodium dodecyl sulfate-polyacrylamide ge l electrophoresis (SDS-PAGE), immunoblotting, and radioligand binding and biologic assays were used to demonstrate autoantibodies against mA ChRs. RESULTS. These autoantibodies recognized by means of SDS-PAGE an d immunoblotting assay a band of approximately 70 kDa expressed on lac rimal gland membranes that comigrated with the peak of labeled mhChRs. Moreover, pSS IgG were able to inhibit, in an irreversible manner, th e binding of [H-3] quinuclidinyl benzilate to mAChRs of rat exorbital lacrimal glands and to simulate the biologic effect of mAChR agonists, because they trigger the activation of phosphoinositide turnover. Atr opine and 4-diphenylacetoxy-N-methylpiperidine methiodide blocked the effect and carbachol mimicked it, confirming that the M-3 subtype mACh Rs mediated pSS IgG action. As control, IgG from sera of women without pSS gave negative results on immunoblotting, binding, and biologic as says, thus demonstrating the specificity of the reaction. CONCLUSIONS. Autoantibodies against mAChRs may be considered among the serum facto rs implicated in the pathophysiology of the development of pSS dry eye s.