Muscarinic acetylcholine receptor antibodies as a new marker of dry eye Sjögren syndrome.
OBJECTIVE
The authors investigated whether circulating autoantibodies against M(3) 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 M(3) mAChRs. 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 and the synthetic 25-mer peptide, corresponding to the second extracellular loop of human M(3) mAChRs. Moreover, the IgG fraction and the corresponding affinity-purified anti-M(3) peptide autoantibodies from the same patients were able to activate NOS coupled to lacrimal gland M(3) 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.
Bacman
S
S
Pharmacology Unit, School of Dentistry and the Pathology and Pharmacology Department, School of Medicine, Buenos Aires University, Argentina.
Berra
A
A
Sterin-Borda
L
L
Borda
E
E
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000302:isolation & purification; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007765:Lacrimal Apparatus / Q000201:enzymology; D008875:Middle Aged; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010455:Peptides / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D007074:Immunoglobulin G; D010455:Peptides; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat