Distribution of anti-melanoma differentiation associated gene 5 (MDA5) IgG subclasses in MDA5+ dermatomyositis

Distribution of anti-melanoma differentiation associated gene 5 (MDA5) IgG subclasses in MDA5+ dermatomyositis
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抗黑色素瘤分化相关基因 5 (MDA5) IgG 亚类在 MDA5 皮肌炎中的分布。

DOI:
10.1093/rheumatology/keab268
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发表时间:
2022-01-01
期刊:
影响因子:
5.5
通讯作者:
Cao, Hua
Cao, Hua
中科院分区:
医学1区
文献类型:
--
作者:
Chen, Mengya;Zhao, Qian;Cao, Hua

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目标 抗黑色素瘤分化相关基因5(MDA 5)抗体是皮肌炎(DM)和临床无肌病性皮肌炎(CADM)患者间质性肺病(ILD)的主要预测因子。然而,一部分MDA 5+患者预后良好。我们旨在确定使用抗MDA 5抗体同种型和IgG亚类评估ILD风险的可能性。 方法 采用酶联免疫吸附试验(ELISA)检测36例抗-MDA 5阳性的DM/CADM患者血清中抗-MDA 5的IgG、伊加和IgM亚型。进一步研究抗-MDA 5抗体的IgG亚类。基于抗-MDA 5同种型和抗-MDA 5 IgG亚类分析实验室检查结果和累积生存期。 结果 在MDA 5+的DM/CADM患者中,抗MDA 5 IgG、伊加、IgM阳性率分别为100%、97%、6%。抗MDA 5抗体IgG 1、IgG 2、IgG 3和IgG 4的阳性率分别为72%、25%、0%和28%。抗MDA 5 IgG 1+患者的急性间质性肺炎发生率、死亡率和血清铁蛋白水平均显著高于抗MDA 5 IgG 1-DM/CADM患者(P分别为0.0027、0.015、0.0011)。抗MDA 5 IgG 1预测死亡率的敏感性为100%,特异性为41.7%。联合使用抗MDA 5 IgG 1和IgG 4预测死亡率的特异性更好(87.5%)。 结论 伊加和IgG是主要的抗MDA 5抗体同种型。抗MDA 5 IgG 1是MDA 5 IgG亚类的主要成分,抗MDA 5 IgG 1和IgG 4可作为预测DM-ILD死亡率的有用生物标志物。
OBJECTIVES The anti-melanoma differentiation-associated gene 5 (MDA5) antibody is the main predictor of interstitial lung disease (ILD) in dermatomyositis (DM) and clinically amyopathic dermatomyositis (CADM). Nevertheless, a subset of MDA5+ patients have a favorable prognosis. We aimed to determine the possibility of using anti-MDA5 antibody isotypes and IgG subclasses for evaluating ILD risk. METHODS The isotypes (IgG, IgA and IgM) of anti-MDA5 were detected in serum samples of 36 anti-MDA5+ patients with DM/CADM using enzyme-linked immunosorbent assay (ELISA). IgG subclasses of anti-MDA5 antibodies were further investigated. Laboratory findings and cumulative survival were analyzed based on the isotypes of anti-MDA5 and subclasses of anti-MDA5 IgG. RESULTS Among the MDA5+ patients with DM/CADM, the positive rates of anti-MDA5 IgG, IgA, IgM were 100%, 97%, and 6%, respectively. The positive rates of anti-MDA5 IgG1, IgG2, IgG3, and IgG4 were 72%, 25%, 0%, and 28%, respectively. The incidence of acute interstitial pneumonia, mortality rate, and serum ferritin were significantly higher in anti-MDA5 IgG1+ patients than those in anti-MDA5 IgG1- patients with DM/CADM (P = 0.0027, 0.015, 0.0011, respectively). The sensitivity and specificity of anti-MDA5 IgG1 for predicting mortality were 100% and 41.7%, respectively. A combination of anti-MDA5 IgG1 and IgG4 for predicting mortality, yielded better specificity (87.5%). CONCLUSION IgA and IgG are the primary anti-MDA5 antibody isotypes. Anti-MDA5 IgG1 is the primary component of MDA5 IgG subclasses and anti-MDA5 IgG1 and IgG4 might serve as useful biomarkers for predicting mortality in DM-ILD.