抗MDA5抗体对皮肌炎继发间质性肺病的病情活动与预后评估的价值

Value of anti-melanoma differentiation-related gene 5 antibody for assessing disease activity and prognosis in patients with dermatomyositis-associated interstitial lung disease

目的 :观察特发性炎性肌病(idiopathic inflammatory myopathy, IIM)合并间质性肺病(interstitial lung disease, ILD)患者血清中抗黑素瘤分化相关基因5(melanoma differentiation associated gene 5, MDA5)抗体的表达水平,探讨抗MDA5抗体与IIM合并ILD(IIM-ILD)临床特征、严重程度及6个月死亡率之间的关系,为寻找新的免疫干预新途径积累实验数据。方法:采用酶联免疫吸附试验检测104例IIM不合并ILD患者19例和IIM-ILD患者85例[其中多发性肌炎(polymyositis, PM)4例,皮肌炎(dermatomyositis, DM)8例,无肌病性皮肌炎(amyopathic dermatomyositis, ADM)7例, PM-ILD 17例, DM-ILD 25例, ADM-ILD 43例],以及13名正常对照者血清中的抗MDA5抗体水平,分析该抗体与患者肺功能[包括用力肺活量(forced vital capacity, FVC%)]与一口气呼吸法一氧化碳扩散功能(single breath, carbon monoxide diffusing capacity, DLCO/SB)、肺结构包括高分辨率CT评分及半年生存率间的关系。结果 :ADM-ILD患者血清中的抗MDA5抗体水平较正常对照组、IIM不合并ILD组及PM-ILD组明显增高(P<0.005);相比DM-ILD患者,ADM-ILD患者血清中的抗MDA5抗体水平增高(P<0.05);该抗体水平与IIM患者肺功能间无相关性(FVC%,r=-0.044 25,P=0.757 9;DLCO/SB,r=-0.068 39,P=0.633 5),而与肺结构改变呈显著正相关(r=0.387 9,P=0.000 2);抗MDA5阳性DM患者的半年内的生存率与抗MDA5阴性患者相比明显降低(77.55%比100.00%),差异有统计学意义(P=0.000 2)。结论:采用酶联免疫吸附试验测得的血清抗MDA5抗体水平,与DM尤其是ADM合并ILD患者的肺功能、肺结构破坏严重程度及半年生存率密切相关。

Objective: To study the expression level of anti-melanoma differentiation gene 5 antibody(anti-MDA5 antibody) in serum of idiopathic inflammatory myopathy(IIM) patients associated with interstitial lung disease(ILD), and to explore the relationship between anti-MDA5 antibody and clinical characteristics, severity and 6-month mortality of IIMILD patients for providing laboratory evidences to delineate new immune intervention pathway. Methods: The expression of anti-MDA5 antibody in serum of 104 patients with IIM or IIM-ILD, including polymyositis 4 cases, dermatomyositis 8 cases, amyopathic dermatomyositis, 7 cases, polymyositis-ILD 17 cases, dermatomyositis-ILD 25 cases, amyopathic dermatomyositis-ILD 43 cases, and normal control group was detected by ELISA, and the relationships between anti-MDA5 antibody and lung function [FVC% and DLCO/SB(single breath, carbon monoxide diffusing capacity)], lung structure[HRCT score(high resolution CT score)] and 6-month survival were analyzed. Results: In patients with amyopathic dermatomyositis(ADM), the serum level of anti-MDA5 antibody was higher than that of normal controls, patients with dermatomyositis(DM), IIM not associated with ILD and polymyositis(PM) with ILD(P<0.005). Compared with DM-ILD patients, the serum level of anti-MDA5 antibody in patients with ADM-ILD was increased(P<0.05). There was no correlation between anti-MDA5 antibody level and lung function in patients with IIM(FVC% r=-0.04425 P=0.7579, DLCO/SB,r=-0.06839 P=0.6335), and was positively correlated with lung structural changes(r=0.3879 P=0.0002). The 6-month mortality of IIM patients with positive anti-MDA5 antibody was significantly different from that of anti-MDA5 antibody negative patients(P=0.0002). Conclusions: The anti-MDA5 antibody level detected by ELISA is closely correlated with lung function, severity of lung structural damage and mortality in patients with DM-ILD, especially ADM-ILD.