原发性干燥综合征患者体内存在抑制胃肠蠕动的自身抗体
发表者：作者：Park K，翻译：柴静，审校：赵金霞
日期：2015-02-27
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摘要：包括胃排空延迟和结肠蠕动障碍在内的胃肠道功能损伤是原发性干燥综合征（SS）患者的常见表现。但是，其病理机制目前仍不十分明确。该研究目的为探究毒蕈碱受体功能性自身抗体在原发性干燥综合征胃肠道功能紊乱发病中的作用。通过比较应用IgG前后卡巴胆碱（CCh）或电场刺激（EFS）诱导的肌肉收缩幅度，评价干燥综合征或者正常免疫球蛋白G（IgG）对平滑肌运动的影响。毒蕈碱受体3（M3R）在结肠和胃平滑肌收缩中具有重要作用，而M2R部分参与胃部平滑肌收缩。从4个原发性干燥综合征患者血清中所提取的IgG（SS- IgG）1mg/ml孵育结肠及胃部平滑肌条1小时能够明显抑制不同浓度卡巴胆碱所诱导的平滑肌收缩，而从健康对照组所得到的IgG几乎无效果。SS-IgG孵育结肠平滑肌条后也能抑制电场刺激所诱导的结肠肌肉收缩，这一过程可被毒蕈碱受体3选择性阻滞剂4-DAMP所模拟。NK1拮抗剂SR1403330对电场刺激所介导的结肠平滑肌收缩几乎无作用。这些结果表明从原发性干燥综合征患者中所分离的自身抗体能够抑制小鼠结肠和胃部毒蕈碱受体所介导的胆碱能神经传递，从而为解释原发性干燥综合征患者胃肠功能紊乱提供了线索。
附原文：Abstract 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.
引自: Park K, Park S, Jackson MW.The inhibitory effects of antimuscarinic autoantibodies in the sera of primary Sjogren syndrome patients on the gastrointestinal motility.MolImmunol. 2013 Dec;56(4):583-7 （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）
附原文：Abstract 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.
引自: Park K, Park S, Jackson MW.The inhibitory effects of antimuscarinic autoantibodies in the sera of primary Sjogren syndrome patients on the gastrointestinal motility.MolImmunol. 2013 Dec;56(4):583-7 （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）