Division of Respiratory Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
Clinical and Translational Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan.
Clin Rheumatol. 2020 Jul;39(7):2171-2178. doi: 10.1007/s10067-020-04984-x. Epub 2020 Feb 13.
INTRODUCTION/OBJECTIVES: Interstitial lung disease (ILD) is a significant cause of mortality among patients with dermatomyositis (DM) or polymyositis (PM). There are two subtypes of PM and DM often complicated with ILD: those with anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies and those with anti-MDA-5-associated amyopathic DM (ADM). Our aim is to clarify the inflammatory and immunological differences between the disorders.
We retrospectively collected consecutive patients with anti-ARS-ILD and those with anti-MDA-5 antibody-positive ADM-ILD. The serum concentration of 38 cytokines was measured using a cytokine panel. The relative risks for anti-MDA-5 antibody-positive ADM-ILD were examined with univariate and multivariate logistic regression models. Spearman's rank correlation coefficient was calculated between cytokine levels and clinical parameters in the disease. Levels of cytokines were compared between anti-ARS-ILD and anti-MDA-5-positive ADM-ILD patients (alive or dead) using Dunnett's test.
Twenty-three patients with anti-ARS-ILD and the same number of patients with anti-MDA-5-positive ADM-ILD were enrolled. The anti-MDA-5 group had poor survival (p = 0.025). Univariate logistic regression models showed that eotaxin, IL-10, IP-10, and MCP-1 were associated with the diagnosis of anti-MDA-5-positive ADM-ILD. Multivariate logistic regression models revealed that IP-10 was the most significantly associated (p = 0.001). Relationship analyses showed that IL-10 had significant positive correlations with CK (r = 0.5267, p = 0.009) and ferritin (r = 0.4528, p = 0.045). A comparison of the cytokine levels found that IP-10 was elevated in both patients who were alive and patients who had died with ADM-ILD compared with the levels in those with ARS-ILD (p = 0.003 and p = 0.001, respectively).
Anti-MDA-5-positive ADM-ILD had poorer survival than anti-ARS-ILD. IP-10 seems to be most deeply involved in the pathophysiology of anti-MDA-5-associated ADM-ILD.Key Points• To clarify differences in the inflammatory and immunological features of anti-MDA-5-positive ADM-ILD and anti-ARS-ILD, we performed an observational study to measure serum cytokine concentrations before treatment using a multiplex immunoassay system.• Multivariate logistic regression models revealed that IP-10 was associated with the most significant relative risk for ADM-ILD with anti-MDA-5 antibodies.• Levels of IP-10 were elevated considerably in anti-MDA-5-positive survivors and nonsurvivors compared with the levels in anti-ARS patients.• These results suggest that IP-10 is the most deeply involved in the pathophysiology of anti-MDA-5-positive ADM-ILD.
简介/目的：间质性肺病（ILD）是皮肌炎（DM）或多发性肌炎（PM）患者死亡的重要原因。有两种常伴有ILD的 PM 和 DM 亚型：抗氨酰-tRNA 合成酶（抗-ARS）抗体阳性和抗 MDA-5 相关无肌病性皮肌炎（ADM）。我们的目的是阐明这些疾病之间的炎症和免疫学差异。
我们回顾性收集了抗-ARS-ILD 连续患者和抗-MDA-5 抗体阳性 ADM-ILD 患者。使用细胞因子试剂盒测量 38 种细胞因子的血清浓度。使用单变量和多变量逻辑回归模型检查抗-MDA-5 抗体阳性 ADM-ILD 的相对风险。采用 Spearman 秩相关系数计算疾病中细胞因子水平与临床参数之间的相关性。使用 Dunnett 检验比较抗-ARS-ILD 和抗-MDA-5 阳性 ADM-ILD 患者（存活或死亡）的细胞因子水平。
共纳入 23 例抗-ARS-ILD 患者和相同数量的抗-MDA-5 阳性 ADM-ILD 患者。抗-MDA-5 组的生存状况较差（p=0.025）。单变量逻辑回归模型显示，嗜酸性粒细胞趋化因子（eotaxin）、白细胞介素-10（IL-10）、干扰素诱导蛋白-10（IP-10）和单核细胞趋化蛋白-1（MCP-1）与抗-MDA-5 阳性 ADM-ILD 的诊断相关。多变量逻辑回归模型显示，IP-10 与疾病的相关性最显著（p=0.001）。相关性分析显示，IL-10 与 CK（r=0.5267，p=0.009）和铁蛋白（r=0.4528，p=0.045）呈显著正相关。细胞因子水平的比较发现，与 ARS-ILD 患者相比，存活和死亡的 ADM-ILD 患者的 IP-10 水平均升高（p=0.003 和 p=0.001）。
抗-MDA-5 阳性 ADM-ILD 的生存率低于抗-ARS-ILD。IP-10 似乎与抗 MDA-5 相关 ADM-ILD 的病理生理学关系最为密切。
为了阐明抗-MDA-5 阳性 ADM-ILD 和抗-ARS-ILD 之间炎症和免疫特征的差异，我们进行了一项观察性研究，使用多重免疫分析系统在治疗前测量血清细胞因子浓度。
多变量逻辑回归模型显示，IP-10 与抗 MDA-5 抗体相关 ADM-ILD 的相对风险最显著。
与抗-ARS 患者相比，抗-MDA-5 阳性 ADM-ILD 患者的 IP-10 水平明显升高。
这些结果表明，IP-10 与抗-MDA-5 阳性 ADM-ILD 的病理生理学关系最为密切。
