The inhibitory effects of antimuscarinic autoantibodies in the sera of primary Sjogren syndrome patients on the gastrointestinal motility

• Published in: Molecular immunology Vol. 56; no. 4; pp. 583 - 587
• Main Authors: Park, Kyungpyo, Park, Sowon, Jackson, Michael W.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2013
• Subjects: Animals; Antibodies; Autoantibodies - blood; Autoantibodies - immunology; Autoantibodies - pharmacology; Carbachol (CCh); Carbachol - pharmacology; Cholinergic Agonists - pharmacology; Colon - drug effects; Colon - immunology; Colon - physiology; Diamines - pharmacology; Dose-Response Relationship, Drug; Gastrointestinal Motility - drug effects; Gastrointestinal Motility - immunology; GI dysfunction; Humans; In Vitro Techniques; Male; Mice; Mice, Inbred BALB C; Muscarinic Antagonists - pharmacology; Muscarinic receptor; Muscle Contraction - drug effects; Muscle Contraction - immunology; Muscle, Smooth - drug effects; Muscle, Smooth - immunology; Muscle, Smooth - physiology; Piperidines - pharmacology; Receptor, Muscarinic M2 - agonists; Receptor, Muscarinic M2 - antagonists & inhibitors; Receptor, Muscarinic M2 - immunology; Receptor, Muscarinic M3 - agonists; Receptor, Muscarinic M3 - antagonists & inhibitors; Receptor, Muscarinic M3 - immunology; Sjogren's Syndrome - blood; Sjogren's Syndrome - immunology; Sjögren's syndrome (SS); Stomach - drug effects; Stomach - immunology; Stomach - physiology; SS; GI; Carbachol (CCh); PLC; IgG; Antibodies; CCh; CISC; M3R; 4-DAMP; EFS; NK1; GI dysfunction; Sjögren's syndrome (SS); SM; Muscarinic receptor; gastrointestinal tract; smooth muscle; muscarinic receptor type 3; phospholipase C; immunoglobulin G; neurokinin 1; 1,1-dimethyl-4-diphenyl acetoxy piperidinium iodide; Carbachol; Sjögren's syndrome; carbachol-induced smooth muscle contraction; electrical field stimulation
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2013.06.004

•There are antimuscarinic autoantibodies in primary Sjogren syndrome patients’ sera.•SS autoantibodies inhibit muscarinic receptor function in mouse colon and stomach.•The inhibitory effect of SS autoantibodies is mimicked by the 4-DAMP.
Impairment of gastrointestinal tract (GI) function, including delayed gastric emptying and colonic dysmotility, are common features of primary Sjögren's syndrome (SS). However, the pathogenesis remains largely unknown. The aim of the current study was to investigate the role of functional autoantibodies to the muscarinic receptor in mediating GI dysfunction associated with primary SS. The effect of SS or normal immunoglobulin G (IgG) on smooth muscle (SM) motility was assessed by comparing the amplitude of carbachol (CCh) or electrical field stimulation (EFS) – induced muscle contraction before and after IgG application. Muscarinic receptor type 3 (M3R) played a dominant role in both colon and gastric SM contraction, while M2R was partly involved in gastric smooth muscle contraction. Preincubation for 1h of the colon and gastric SM strips with 1mg/ml purified IgG from the sera of four primary SS patients (SS IgG) significantly inhibited carbachol-induced smooth muscle contraction (CISC) over a range of CCh concentrations, whereas IgG from healthy controls had little effect. Incubation of the colon SM strips with SS IgG also inhibited EFS-induced colon muscle contraction, which was mimicked by the M3R-selective blocker, 4-DAMP. SR1403330, an NK1 antagonist, had little effect on EFS-mediated colonic SM contraction. The results suggest that autoantibodies isolated from primary SS patients’ sera inhibit muscarinic receptor-mediated cholinergic neurotransmission in mouse colon and stomach, which may provide clues for explaining the GI dysfunction seen in patients with primary SS.