癌胚抗原和抗MDA5抗体阳性皮肌炎相关间质性肺疾病预后相关性研究

Prognostic correlation between serum carcinoembryonic antigen and Anti-MDA5 positive dermatomyositis with interstitial lung disease

目的观察血清癌胚抗原(carcinoembryonic antigen,CEA)与抗黑色素瘤分化相关基因5(melanoma differentiation associated gene 5,MDA5)抗体阳性皮肌炎相关间质性肺疾病(interstitial lung disease,ILD)患者预后相关性关系。方法回顾性收集四川大学华西医院2017年2月—2019年9月确诊为抗MDA5抗体阳性皮肌炎214例患者临床资料,实验室检查,影像学检查并进行随访。根据CEA水平将患者分为CEA升高组(CEA≥4.63 ng/mL)和CEA正常组(CEA<4.63 ng/mL)。采用R4.1.2软件对所有数据进行统计分析,Kaplan-Meier法绘制生存曲线。对合并ILD患者采用Cox比例风险模型进行生存分析,探索抗MDA5抗体阳性皮肌炎合并ILD患者的死亡影响因素。结果符合纳入排除标准的合并ILD患者共180例,57例为快速进展肺间质纤维化(rapidly progressive pulmonary interstitial fibrosis,RPILD),123例为非RPILD;其中女121例,男59例,平均年龄(50.2±10.7)岁;平均随访23.5个月,死亡52例。单因素分析提示CEA≥4.63 ng/mL、吸烟、合并RPILD、乳酸脱氢酶(lactate dehydrogenase,LDH)≥321 IU/L、白蛋白<30 g/L及伴有呼吸困难是抗MDA5皮肌炎合并ILD患者死亡危险因素。多因素Cox回归分析提示CEA≥4.63 ng/mL[风险比(hazard ratio,HR)=3.01,95%可信区间(confidence interval,CI)1.23~7.32,P=0.015]、合并RPILD(HR=3.87,95%CI 2.09~7.19,P<0.001)、吸烟(HR=2.37,95%CI 1.25~4.47,P=0.008)、LDH≥321 IU/L(HR=2.47,95%CI 1.23~4.96,P=0.011)、白蛋白<30 g/L(HR=2.57,95%CI 1.38~4.78,P=0.003)是影响患者远期预后的独立因素。结论CEA升高可作为抗MDA5抗体阳性皮肌炎合并ILD患者不良预后的临床指标。合并RPILD、吸烟、LDH≥321 IU/L、白蛋白<30 g/L是抗MDA5抗体阳性皮肌炎相关间质性肺炎患者死亡的独立危险因素。

Objective To evaluate the clinical relationship between serum carcinoembryonic antigen(CEA)and mortality of anti-melanoma differentiation associated gene 5(MDA5)antibody positive dermatomyositis with interstitial lung disease(ILD).Methods The consecutive clinical data of 214 patients with anti MDA5 antibody positive dermatomyositis from West China Hospital of Sichuan University from February 2017 to September 2019 were collected retrospectively,including demographic,laboratory examination and imaging examination data.Patients were divided into CEA elevated group(CEA≥4.63 ng/mL)and CEA normal group(CEA<4.63 ng/mL)according to CEA level.R4.1.2 software was used for statistical analysis of all data,and Kaplan Meier method was used to draw the survival curve.Cox proportional hazard model was used to analyze the survival of patients with ILD,and to explore the risk factors associated with the survival of patients with anti-MDA5 antibody positive dermatomyositis with ILD.Results There were 180 patients with ILD who met the inclusion and exclusion criteria,57 patients with rapidly progressive pulmonary interstitial fibrosis(RPILD),and 123 patients without RPILD;121 women and 59 men,with an average age of 50.2±10.7 years;The average follow-up was 23.5 months,and 52 patients died.Univariable analysis suggested that CEA≥4.63 ng/mL,smoking,RPILD,lactate dehydrogenase(LDH)≥321 IU/L,albumin<30 g/L and dyspnea were risk factors associated with death in patients with anti MDA5 dermatomyositis combined with ILD.Multivariable Cox regression analysis showed that CEA≥4.63 ng/mL[hazard ratio(HR)=3.01,95%confidence interval(CI)1.23-7.32,P=0.015],RPILD(HR=3.87,95%CI 2.09-7.19,P<0.001),smoking(HR=2.37,95%CI 1.25-4.47,P=0.008),LDH≥321 IU/L(HR=2.47,95%CI 1.23-4.96,P=0.011),albumin<30 g/L(HR=2.57,95%CI 1.38-4.78,P=0.003)were independent predictors for mortality.Conclusions Serum CEA level can be used as a clinical prognostic predictor in patients with anti-MDA5 positive dermatomyositis and ILD.RPILD,smoking,LDH≥321 IU/L,and albumin<30 g/L are independent predictors for mortality.