Successful classification of macrophage-mannose receptor CD206 in severity of anti-MDA5 antibody positive dermatomyositis associated ILD
Successful classification of macrophage-mannose receptor CD206 in severity of anti-MDA5 antibody positive dermatomyositis associated ILD
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DOI：
10.1093/rheumatology/kez185
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发表时间：
2019-12-01
期刊：
影响因子：
5.5
通讯作者：
Suda, Takafumi
中科院分区：
文献类型：
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作者：
Horiike, Yasuoki;Suzuki, Yuzo;Suda, Takafumi
目标。巨噬-甘露糖受体CD206是巨噬细胞选择性活化的标志物。活化的巨噬细胞在糖尿病中起关键作用。间质性肺病（ILD）是糖尿病/临床淀粉样病变（CADM）患者死亡的主要原因。特别是，患有抗黑色素瘤差异基因5抗体（MDA5）的患者经常发展为致命的快速进行性ILD。本研究旨在评估替代活化巨噬细胞在具有抗mda5抗体（MDA5-CADM/DM-ILD）的CADM/DM-ILD患者中的临床意义。我们测量了33名MDA5-CADM/DM-ILD患者和36名年龄和性别匹配的对照组的血清可溶性CD206 （sCD206）浓度。同时检测MDA5-CADM/DM-ILD肺组织中CD206的表达水平。MDA5-CADM/DM-ILD患者的sCD206水平高于对照组（P < 0.0001）。在33例患者中，10例MDA5-CADM/DM-ILD患者发生致命性呼吸衰竭。致死性ILD患者的sCD206浓度显著高于幸存者，sCD206水平升高与较高的死亡率相关（Log-rank检验，P = 0.0009）。经年龄和性别调整的logistic回归分析显示，sCD206是MDA5-CADM/DM-ILD的独立预后因素。重要的是，sCD206联合PaO2的评估根据预后成功分为三组（P < 0.005）。病理分析显示，死亡病例的肺中cd206阳性巨噬细胞的积累比非死亡病例的多。MDA5-CADM/DM-ILD患者血清sCD206水平升高，且与预后不良相关。sCD206是预测MDA5-CADM/DM-ILD严重程度的潜在生物标志物。
Objectives. Macrophage-mannose receptor, CD206, is a marker of alternatively activated macrophages. Activated macrophages play key roles in DM. Interstitial lung disease (ILD) is a leading cause of mortality in patients with DM/clinically amyopathic DM (CADM). In particular, patients with the anti-melanoma differential gene 5 antibody (MDA5) frequently develop fatal rapid progressive ILD. This study aimed to evaluate the clinical implications of alternatively activated macrophages in patients with CADM/DM-ILD with anti-MDA5 antibody (MDA5-CADM/DM-ILD).Methods. We measured serum concentrations of soluble CD206 (sCD206) in 33 patients with MDA5-CADM/DM-ILD and 36 age- and sex-matched control subjects. Expression levels of CD206 in the lungs from MDA5-CADM/DM-ILD were also examined.Results. Patients with MDA5-CADM/DM-ILD had higher levels of sCD206 than those in controls (P < 0.0001). Of the 33 patients, 10 MDA5-CADM/DM-ILD patients developed fatal respiratory failure. Concentrations of sCD206 in patients with fatal ILD cases were significantly higher than those in the survivors, and increased sCD206 levels were associated with a higher mortality rate (Log-rank test, P = 0.0009). Age- and gender-adjusted logistic regression analyses showed that sCD206 was an independent prognostic factor for MDA5-CADM/DM-ILD. Importantly, assessment by sCD206 together with PaO2 successfully divided into three groups by their prognosis (P < 0.005, respectively). Pathological analyses showed accumulations of CD206-positive macrophages in lungs from the fatal case rather than those in the non-fatal cases.Conclusions. Levels of serum sCD206 are increased in MDA5-CADM/DM-ILD and associated with poor prognosis. sCD206 is a potential biomarker to predict the severity of MDA5-CADM/DM-ILD.