Department of Neuroimmunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Clinical Research, Nagasaki Kawatana Medical Center, Nagasaki, Japan.
Arthritis Res Ther. 2020 Feb 21;22(1):32. doi: 10.1186/s13075-020-2128-z.
Patients with systemic sclerosis (SSc) complicated by gastrointestinal dysmotility are difficult to treat and have high mortality. To clarify the pathogenesis of gastrointestinal manifestations, we aimed to demonstrate the association among the clinical features of SSc, the serological markers, the autoantibodies against nicotinic acetylcholine receptor at autonomic ganglia (gAChR).
Fifty patients were enrolled and divided into two groups according to the presence or absence of gastrointestinal manifestations, and the characteristics were analyzed between these two groups. We measured biomarkers and the autoantibodies against two gAChRα3 and β4 subunits to test sera samples. Furthermore, patients were classified based on the presence or absence of anti-gAChR autoantibodies, and their clinical features were compared.
In patients with SSc and gastrointestinal manifestations, digital ulcers were more frequent (p = 0.050) and VEGF expression was significantly higher (p = 0.038). Seven subjects with SSc were seropositive for α3 subunit, whereas one patient was seropositive for β4 subunit. The mean level of anti-gAChRα3 autoantibodies in SSc patients with gastrointestinal manifestations was significantly higher than that in SSc patients without gastrointestinal manifestations (p = 0.001). The group of patients with SSc and gAChR autoantibodies had significantly higher endostatin levels (p = 0.046).
This study is the first to demonstrate that clinical characteristics of SSc patients with seropositivity for gAChR autoantibodies. Patients with SSc have circulating autoantibodies against gAChR, which may contribute to gastrointestinal manifestations associated with this disease, suggesting that gAChR-mediated autonomic neurotransmission may provide a pathomechanism for gastrointestinal dysmotility in SSc.
伴有胃肠动力障碍的系统性硬化症（SSc）患者治疗困难，死亡率高。为了阐明胃肠表现的发病机制，我们旨在展示 SSc 的临床特征、血清标志物、自主神经节烟碱型乙酰胆碱受体（gAChR）自身抗体之间的关联。
共纳入 50 例患者，根据是否存在胃肠表现分为两组，分析两组间的特征。我们测量了生物标志物和针对两个 gAChRα3 和β4 亚基的自身抗体来检测血清样本。此外，根据是否存在抗 gAChR 自身抗体对患者进行分类，并比较其临床特征。
在伴有胃肠表现的 SSc 患者中，手指溃疡更为常见（p=0.050），VEGF 表达显著升高（p=0.038）。7 例 SSc 患者血清抗 gAChRα3 亚基阳性，1 例患者血清抗 gAChRβ4 亚基阳性。伴有胃肠表现的 SSc 患者抗 gAChRα3 自身抗体的平均水平明显高于无胃肠表现的 SSc 患者（p=0.001）。伴有 gAChR 自身抗体的 SSc 患者的内皮抑素水平显著升高（p=0.046）。
本研究首次证明了 gAChR 自身抗体阳性的 SSc 患者的临床特征。SSc 患者存在针对 gAChR 的循环自身抗体，可能导致与该疾病相关的胃肠表现，提示 gAChR 介导的自主神经传递可能为 SSc 中的胃肠动力障碍提供一种发病机制。
