Autoantibodies against cerebral muscarinic cholinoceptors in Sjögren syndrome: functional and pathological implications.
Previous studies have demonstrated that antibodies against muscarinic acetylcholine receptors (mAChRs) from exocrine glands, correlates with Sjögren syndrome (SS) in the majority of patients. The aim of the present investigation was to establish if serum IgG antibodies present in SS interacts with cerebral mAChRs. Results show that anti-cerebral IgG are present in the sera of 40% SS patients studied. Autoantibodies were able to interact with mAChRs of cerebral frontal cortex membranes inhibiting the [(3)H]QNB binding to its specific receptor. Moreover, tested by ELISA and dot blot they recognized the synthetic peptides corresponding to the second extracellular loop of human M(1) and M(3) mAChR. In addition, the corresponding affinity-purified anti-M(1) and anti-M(3) peptide IgGs displayed an agonistic activity, stimulating phosphoinositide hydrolysis. The results support the notion that serum IgG autoantibodies in SS patients target cerebral mAChRs may have some role in the pathogenesis of higher cognitive dysfunction present in SS patients.
Reina
Silvia
S
Pharmacology Unit, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
Sterin-Borda
Leonor
L
Orman
Betina
B
Borda
Enri
E
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D001666:Binding Sites, Antibody / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D005260:Female; D005625:Frontal Lobe / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000096:biosynthesis; D017433:Protein Structure, Secondary; D051381:Rats; D043643:Receptor, Muscarinic M1 / Q000276:immunology* / Q000502:physiology; D043587:Receptor, Muscarinic M3 / Q000276:immunology* / Q000502:physiology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000473:pathology*; D015854:Up-Regulation / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D010716:Phosphatidylinositols; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3