血清抗黑色素瘤分化相关基因抗体检测在多发性肌炎/皮肌炎患者中的意义

目的 检测多发性肌炎/皮肌炎(PM/DM)患者血清抗黑色素瘤分化相关基因(MDA5)抗体水平,探讨其在多发性肌炎/皮肌炎患者中的意义.方法 采用酶联免疫吸附试验(ELISA)法测定113例多发性肌炎/皮肌炎、30例系统性红斑狼疮(SLE),30例类风湿关节炎(RA),15例原发性干燥综合征(pSS),21例急性肺部感染患者以及50名健康对照组血清中抗MDA5抗体的阳性率.统计学方法采用t检验、Mann-Wittney U检验、X2检验、Fisher检验及Logistic多因素回归分析.结果 血清抗MDA5抗体的阳性率在多发性肌炎组、皮肌炎组、SLE组、RA组、SS组、肺部感染组及健康对照组分别是0、22.6％、3.3％、3.3％、0、0和0.皮肌炎组血清抗MDA5抗体阳性率(22.6％)明显高于多发性肌炎患者(0,P＜0.01),亦高于SLE患者(3.3％,X2=5.68,P＜0.05)、RA患者(3.3％,X2=5.68,P＜0.05)、pSS患者(0,P＜0.05)、肺部感染患者(0,P＜0.05)及健康对照(0,P＜0.01).皮肌炎亚组中,临床无肌病性皮肌炎(CADM)患者抗MDA5抗体阳性率(62.5％)较经典皮肌炎( CDM)患者高(18.4％,P＜0.05).抗MDA5抗体阳性的皮肌炎患者关节炎、发热、Ⅴ字疹、癌胚抗原升高、CA153升高的发生率及血清谷氨酰转肽酶(GGT)、铁蛋白浓度较抗MDA5抗体阴性患者显著升高(X2=4.08,8.06,6.357,32.4,4.867；Z=-2.86,-2.44；P均＜0.05)；而抗核抗体阳性、血清肌酸激酶浓度及外周血T细胞、自然杀伤细胞计数则低于抗MDA5阴性组(X2=4.08;Z=-2.072,-2.013,-2.907；P均＜0.05).此外,抗MDA5抗体阳性的皮肌炎患者急性/亚急性间质性肺炎(A/SIP)的发生率(78.9％)显著高于阴性患者(3.2％)(P＜0.01).抗MDA5抗体诊断皮肌炎合并A/SIP的敏感性为88.2％,特异性为94％.多因素分析发现血清抗MDA5阳性为皮肌炎合并间质性肺疾病(ILD)患者死亡的独立危险因素(0R=8.46,95％CI 1.77～40.36,P＜0.01).结论 在我国多发性肌炎/皮肌炎患者人群,血清抗MDA5抗体主要存在于皮肌炎患者,是皮肌炎合并A/SIP的敏感及特异性血清学指标,也是皮肌炎合并ILD死亡的独立危险因素.

Anti-MDA5 antibody is associated with acute/subacute interstitial pneumonia and predicts poor prognosis for interstitial lung diseases in patients with dermatomyositis

Objective To determine the serum MDA5 levels and their clinical associations in patients with polymyositis/dermatomyositis (PM/DM).Methods Serum anti-MDA5 antibody was detected by ELISA in 119 adult PM/DM patients,30 patients with systemic lupus erythematosus (SLE),30 patients with rheumatoid arthritis (RA),15 patients with primary Sj(O)gren's syndrome (SS),21 patients with pulmonary infection and 50 healthy controls.t-test,Mann-Whitney U test or chi-square test or Fisher exact test as well as Logistic multivariate regression analysis were carried out to compare the results of this study.Results Serum antiMDA5 antibody positive rate in DM patients (22.6％) were significantly higher compared with that of patients with PM (0,P＜0.01),patients with SLE (3.3％,X2=5.68,P＜0.05),RA (3.3％,X2=5.68,P＜0.05),pSS (0,P＜0.05) and pulmonary infection(0,P＜0.05) and healthy controls (0,P＜0.01).In the DM subgroup,CADM patients presented a higher positive anti-MDA5 antibody rate than classic DM patients.The incidence of arthritis,fever,vrash raised CEA and CA153 level,and serum concentration of GGT and ferritin were significantly higher in the anti-MDA5 positive DM group than anti-MDA5 negative DM group (X2=4.08,8.06,6.357,32.4,4.867; Z=-2.86,-2.44; P value of all these tests were less than 0.05 ),while the rate of serum positive ANA,serum level of CK and T,NK cell counts in the peripheral blood were much lower than those in anti-MDA5 negative DM group (X2=4.08; Z=-2.072,-2.013,-2.907; all P＜0.05).Moreover,the incidence of acute/subacute interstitial pneumonia (A/SIP) was significantly higher in anti-MDA5 positive DM patients than anti-MDA5 negative DM patients.The sensitivity and specificity of anti-MDA5 antibody for diagnosing A/SIP in DM patients were 88.2％ and 94％ respectively.Additionally,logistic multivariate analysis showed that anti-MDA5 was an independent risk factor for death of interstitial lung diseases (ILD) in DM (OR=8.46,95％CI 1.77～40.36,P＜0.01).Conclusion In Chinese PM/DM patients,serum anti-MDA5 antibody is mainly present in DM patients and is a strong predictor for poor prognosis diagnosis of DM with A/SIP and is an independent risk factor for death of ILD in DM.