Department of Immunology and Rheumatology, Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto 1-7-1, Nagasaki 852-8501, Japan.
Rheumatology (Oxford). 2012 Jul;51(7):1278-84. doi: 10.1093/rheumatology/ker518. Epub 2012 Feb 29.
Interstitial lung disease (ILD), especially rapidly progressive ILD (RPILD), is a major poor prognostic factor in patients with DM. We investigated the association of anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) with clinical characteristics and mortality in Japanese patients with DM.
Seventy-nine DM patients, comprising 58 classic DM and 21 clinically amyopathic DM (CADM) patients, were enrolled. Serum Abs were screened by immunoprecipitation assays, and an immunosorbent assay (ELISA) was used for MDA5. The relationships of clinical characteristics and mortality with each Ab were investigated.
Anti-MDA5 Ab was detected in 17 patients. Anti-clinically amyopathic DM 140 kDa polypeptide Abs (anti-CADM-140 Abs) were found in 16 of the 17 anti-MDA5 Ab(+) patients. Skin ulcers, palmar papules, CADM, RPILD and mediastinal emphysema were widely distributed in anti-MDA5 Ab(+) patients. Mortality at 6 months as well as 5 years was also significantly higher in anti-MDA5 Ab(+) patients than in anti-MDA5 Ab(-) patients. In a multivariable Cox regression analysis, mortality was independently associated with anti-MDA5 Ab (relative hazard 6.33; 95% CI 1.43, 28.0). All of the deaths in anti-MDA5 Ab(+) patients were attributed to respiratory failure of RPILD; however, RPILD did not worsen in any of the anti-MDA5 Ab(+) patients who survived the first 6 months.
The presence of anti-MDA5 Ab identifies the characteristic skin, musculoskeletal, pulmonary and prognostic features in patients with DM. In addition, anti-MDA5 Ab seems to predict a group of patients with CADM-complicated fatal RPILD.
间质性肺病(ILD),特别是快速进展性 ILD(RPILD),是 DM 患者预后不良的主要因素。我们研究了抗黑色素瘤分化相关基因 5(MDA5)抗体(Ab)与日本 DM 患者临床特征和死亡率的关系。
纳入 79 例 DM 患者,包括 58 例经典 DM 和 21 例临床肌病型 DM(CADM)患者。通过免疫沉淀法筛查血清 Ab,采用酶联免疫吸附法(ELISA)检测 MDA5。研究了每种 Ab 与临床特征和死亡率的关系。
在 17 例患者中检测到抗-MDA5 Ab。在 17 例抗-MDA5 Ab(+)患者中,发现 16 例存在抗临床肌病型 DM 140 kDa 多肤 Ab(抗-CADM-140 Ab)。抗-MDA5 Ab(+)患者广泛存在皮肤溃疡、手掌丘疹、CADM、RPILD 和纵隔气肿。抗-MDA5 Ab(+)患者的 6 个月和 5 年死亡率也明显高于抗-MDA5 Ab(-)患者。多变量 Cox 回归分析显示,死亡率与抗-MDA5 Ab 独立相关(相对危险度 6.33;95%CI 1.43,28.0)。所有抗-MDA5 Ab(+)患者的死亡均归因于 RPILD 的呼吸衰竭;然而,在抗-MDA5 Ab(+)患者中,没有任何患者在存活的 6 个月内发生 RPILD 恶化。
抗-MDA5 Ab 的存在可识别 DM 患者的特征性皮肤、肌肉骨骼、肺部和预后特征。此外,抗-MDA5 Ab 似乎预测了一组伴有 CADM 合并致命性 RPILD 的患者。