抗黑色素瘤分化相关基因5抗体阳性皮肌炎危险因素分析及早期诊断

Risk factors analysis and early diagnosis of anti-melanoma differentiation associated gene 5 antibody positive dermatomyositis

目的探讨抗黑色素瘤分化相关基因5(MDA5)抗体阳性DM患者的独立危险因素及早期诊断。方法回顾性分析2012年1月至2021年6月徐州医科大学附属医院风湿免疫科收治的DM患者223例作为研究对象,根据抗MDA5抗体是否阳性分为抗MDA5抗体阳性组(34例)和抗MDA5抗体阴性组189例,比较2组患者的一般资料、临床表现及实验室检查结果。用二元Logistic回归法分析抗MDA5抗体阳性DM患者的危险因素,绘制受试者工作特征曲线(ROC),评估各危险因素对抗MDA5抗体阳性DM患者的预测价值。结果抗MDA5抗体阳性组的皮肤溃疡发生率[20.6%(7/34)和9.0%(17/189),χ^(2)=4.03,P=0.045]、抗Ro52抗体阳性率[61.8%(21/34)和21.2%(40/189),χ^(2)=23.90,P<0.001]、间质性肺疾病(ILD)[91.2%(31/34)和38.6%(73/189),χ^(2)=31.98,P<0.001]及快速进展性间质性肺疾病(RP-ILD)发生率[67.6%(23/34)和5.3%(10/189),χ^(2)=88.87,P<0.001]、D-二聚体[1.87(1.23,2.56)μg/ml和1.15(0.59,1.29)μg/ml,χ^(2)=4.68,P<0.001]、血清铁蛋白水平[931.65(579.12,1160.43)ng/ml和507.40(200.40,588.55)ng/ml,χ^(2)=5.60,P<0.001]均高于抗MDA5抗体阴性组,而肌酸激酶(CK)水平显著低于抗MDA5抗体阴性组[85.50(61.25,155.00)U/L和263.00(66.50,1111.14)U/L,χ^(2)=3.08,P=0.002]。多因素Logistic回归分析显示,抗Ro52抗体阳性[OR(95%CI)=5.027(1.632,15.483),P=0.005]、D-二聚体水平升高[OR(95%CI)=1.665(1.124,2.466),P=0.011]、发生ILD[OR(95%CI)=10.071(2.061,49.207),P=0.004]及RP-ILD[OR(95%CI)=10.910(3.294,36.134),P<0.001]是抗MDA5抗体阳性DM患者的独立危险因素。ROC曲线显示,抗Ro52抗体、D-二聚体、ILD及RP-ILD的曲线下面积(95%CI)分别为[0.703(0.615,0.791)、0.752(0.661,0.843)、0.763(0.703,0.822)、0.812(0.730,0.893)](P均<0.001),预测抗MDA5抗体阳性DM的价值均较高。结论抗Ro52抗体阳性、D-二聚体水平升高、发生ILD及RP-ILD是抗MDA5抗体阳性DM患者的独立危险因素,且对抗MDA5抗体阳性DM患者均有一定的早期诊断价值。

Objective To explore the independent risk factors and early diagnosis of dermatomyositis(DM)with positive anti-melanoma differentiation associated gene 5(MDA5)antibody.Methods A total of 223 DM patients admitted to the Department of Rheumatology and Immunology,Affiliated Hospital of Xuzhou Medical University from January 2012 to June 2021 were retrospectively analyzed,according to whether the anti-MDA5 antibody was positive or not,the patients were divided into anti-MDA5 antibody positive group(n=34)and anti-MDA5 antibody negative group(n=189).The demographic data,clinical manifestations and laboratory test results of the two groups were compared.The risk factors of DM patients with positive anti-MDA5 antibody were analyzed by binary Logistic regression,and the receiver operating characteristic curve(ROC)was drawn to evaluate the predictive value of various risk factors for anti-MDA5 antibody positive DM patients.Results The incidence of skin ulcer[20.6%(7/34)vs 9.0%(17/189),χ^(2)=4.03,P=0.045],the positive rate of anti-Ro52 antibody[61.8%(21/34)vs 21.2%(40/189),χ^(2)=23.90,P<0.001],the incidence of interstitial lung disease(ILD)[91.2%(31/34)vs 38.6%(73/189),χ^(2)=31.98,P<0.001]and rapidly progressive interstitial lung disease(RP-ILD)[67.6%(23/34)vs 5.3%(10/189),χ^(2)=88.87,P<0.001],the levels of D-dimer[1.87(1.23,2.56)μg/ml vs 1.15(0.59,1.29)μg/ml,χ^(2)=4.68,P<0.001]and serum ferritin(SF)[931.65(579.12,1160.43)ng/ml vs 507.40(200.40,588.55)ng/ml,χ^(2)=5.60,P<0.001]in the anti-MDA5 antibody positive group were higher than those in the anti-MDA5 antibody negative group,wherease the creatine kinase(CK)level in the anti-MDA5 anti-body positive group was significantly lower than that in the anti-MDA5 antibody negative group[85.50(61.25,155.00)U/L vs 263.00(66.50,1111.14)U/L,χ^(2)=3.08,P=0.002].Multivariate Logistic regression analysis showed that positive anti-Ro52 antibody[OR(95%CI)=5.027(1.632,15.483),P=0.005],increased D-dimer level[OR(95%CI)=1.665(1.124,2.466),P=0.011],occurrence of ILD[OR(95%CI)=10.071(2.061,49.207),P=0.004]and RP-ILD[OR(95%CI)=10.91(3.294,36.134),P<0.001]were independent risk factors for anti-MDA5 antibody positive DM patients.The ROC curve showed that the areas under the curve(95%CI)of anti-Ro52 antibody,D-dimer,ILD and RP-ILD were 0.703(0.615,0.791),0.752(0.661,0.843)],0.763(0.703,0.822),0.812(0.730,0.893)respectively.The P value of all these parameters were<0.001 and their value in predicting anti-MDA5 antibody positive DM was high.Conclusion Positive anti-Ro52-Ab,increased D-dimer level,presence of ILD and RP-ILD are independent risk factors for anti-MDA5 antibody positive DM patients,and they have certain early diagnostic value for DM patients with positive anti-MDA5 antibody.