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

doi:10.16150/j.1671-2870.2019.02.007

摘要/Abstract

摘要：

目的：观察特发性炎性肌病（idiopathic inflammatory myopathy, IIM）合并间质性肺病（interstitial lung di- sease, 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。

关键词: 皮肌炎, 间质性肺炎, 抗黑素瘤分化相关基因5抗体, 临床特征

Abstract:

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 IIM-ILD 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 43cases, 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.

Key words: Dermatomyositis, Interstitial lung disease, Anti-MDA5 antibody, Clinical features

中图分类号:

R563.13

王娟, 王楷文, 赵江峰. 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[J]. 诊断学理论与实践, 2019, 18(2): 155-159.

WANG Juan, WANG Kaiwen, ZHAO Jiangfeng. Value of anti-melanoma differentiation-related gene 5 antibody for assessing disease activity and prognosis in patients with dermatomyositis-associated interstitial lung disease[J]. Journal of Diagnostics Concepts & Practice, 2019, 18(2): 155-159.

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参考文献 13

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参数	IIM(n=19)			IIM-ILD(n=85)
参数	PM（n=4）	DM（n=8）	ADM（n=7）	PM-ILD（n=17）	DM-ILD（n=25）	ADM-ILD（n=43）
年龄 (岁)	58.25±11.59	44.75±22.80	34.14±17.59	53.71±11.33	53.72±8.63	49.26±12.30
女性%	75.00	50.00	85.71	82.35	52.00	72.09
病程(年)	3.03±2.00	0.91±0.89	0.97±1.06	1.42±1.83	1.22±1.51	1.34±1.64
ILD病程 (年)	/	/	/	0.88±1.14	1.03±1.18	1.14±1.57
C反应蛋白 (mg/L)	2.92±0.63	2.74±3.23	3.20±1.43	6.73±7.17	18.01 ± 40.74	11.93±22.61
红细胞沉降率(mm/h)	14.33±11.68	30.20±29.18	17.83±10.13	16.41±13.77	27.71±29.36	28.59±19.94
肌酸激酶 (U/mL)	755.33±835.45	306.20±230.38	55.50±62.29	905.00±1106.49	592.22±1244.29	87.83±133.51
铁蛋白 (ng/mL)	358.03±398.49	487.34±450.09	189.68±198.49	536.19±944.29	938.51±1108.23	1,238.72±1430.43
抗MDA5抗体阳性率 (%)	0 (0.00%)	1 (12.50%)	2 (28.57%)	2 (11.76%)	11 (44.00%)	36 (83.72%)
抗ARS抗体阳性率 (%)	0 (0.00%)	1 (12.50%)	0 (0.00%)	8 (47.06%)	9 (36.00%)	3 (6.98%)
涎液化糖链抗原(U/mL)	741.00±672.02	1,150.75±2019.28	358.14±193.72	1,107.59±2329.15	1,482.60±1787.08	1,146.86±975.08
用力肺活量（%）	92.37±10.68	99.23±13.97	89.40±12.80	68.53±16.05	71.86±24.91	65.51±25.11
一氧化碳扩散功能 (mmol·min^-1·kPa^-1)	72.17±24.22	75.23±21.99	70.10±13.08	43.74±17.18	46.39±17.20	48.48±16.32
高分辨率CT评分（分）	/	/	/	109.46±5.43	132.37±32.73	142.16±41.65

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