Du Y, Wu X, Chen M, Wang W, Xv W, Ye L, Wu D, Xue J, Sun W, Luo J, Wu H
Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Department of Clinic Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Clin Exp Immunol. 2017 May;188(2):234-242. doi: 10.1111/cei.12924. Epub 2017 Feb 17.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by extensive immune response, including over-activation of T and B cell development of pathogenic autoantibodies, organ damage induced by the formation and deposition of immune complex and the abnormal elevation of type I interferon. Semaphorin5A (Sema5A) is involved essentially in immune cell regulation and is also implicated in the pathogenesis of autoimmune disorders. We aimed to evaluate the role of Sema5A in patients with SLE. Serum levels of Sema5A were tested by enzyme-linked immunosorbent assay (ELISA) in 152 SLE patients and 48 healthy controls. The message ribonucleic acid (mRNA) expression levels of Sema5A and ADAM metallopeptidase domain 17 (ADAM17) in the peripheral blood mononuclear cells (PBMC) from 43 patients with SLE and 19 healthy controls were detected by the real-time-quantitative polymerase chain reaction (qPCR). Serum Sema5A levels were increased significantly in SLE patients compared with healthy controls (P < 0·001). Elevated levels of Sema5A were correlated positively with 24-h proteinuria excretion (r = 0·558, P < 0·0001), SLE disease activity index (SLEDAI) (r = 0·278, P = 0·0006) and C-reactive protein (CRP) (r = 0·266, P = 0·002), but negatively with planet (PLT) (r = -0·294, P = 0·0003) and complement 3 (C3) (r = -0·287, P = 0·0004) in SLE patients. Patients with elevated Sema5A levels showed higher incidence of rash, serositis and nephritis (P < 0·05 or P < 0·001). Patients with decreased PLT, C3 or positive for proteinuria also showed elevated Sema5A (P < 0·001 or P < 0·05). The mRNA ADAM17 was increased in SLE patients and correlated positively with serum Sema5A levels. Our data demonstrated that elevated serum Sema5A in SLE patients correlated with disease activity and are involved in kidney and blood system damage; ADAM17 might be involved in the release of secreted Sema5A.
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征为广泛的免疫反应，包括T和B细胞过度激活、致病性自身抗体的产生、免疫复合物形成和沉积所导致的器官损伤以及I型干扰素异常升高。信号素5A（Sema5A）主要参与免疫细胞调节，也与自身免疫性疾病的发病机制有关。我们旨在评估Sema5A在SLE患者中的作用。采用酶联免疫吸附测定（ELISA）检测了152例SLE患者和48例健康对照者血清中Sema5A的水平。通过实时定量聚合酶链反应（qPCR）检测了43例SLE患者和19例健康对照者外周血单个核细胞（PBMC）中Sema5A和ADAM金属蛋白酶结构域17（ADAM17）的信使核糖核酸（mRNA）表达水平。与健康对照相比，SLE患者血清Sema5A水平显著升高（P < 0.001）。Sema5A水平升高与24小时蛋白尿排泄量（r = 0.558，P < 0.0001）、SLE疾病活动指数（SLEDAI）（r = 0.278，P = 0.0006）和C反应蛋白（CRP）（r = 0.266，P = 0.002）呈正相关，但与SLE患者的血小板（PLT）（r = -0.294，P = 0.0003）和补体3（C3）（r = -0.287，P = 0.0004）呈负相关。Sema5A水平升高的患者皮疹、浆膜炎和肾炎的发生率更高（P < 0.05或P < 0.001）。血小板、C3降低或蛋白尿阳性的患者Sema5A水平也升高（P <0.001或P < 0.05）。SLE患者中mRNA ADAM17升高，且与血清Sema5A水平呈正相关。我们的数据表明，SLE患者血清Sema5A升高与疾病活动相关，并参与肾脏和血液系统损伤；ADAM17可能参与分泌型Sema5A的释放。
