Successful classification of macrophage-mannose receptor CD206 in severity of anti-MDA5 antibody positive dermatomyositis associated ILD

• Published in: Rheumatology (Oxford, England) Vol. 58; no. 12; pp. 2143 - 2152
• Main Authors: Horiike, Yasuoki, Suzuki, Yuzo, Fujisawa, Tomoyuki, Yasui, Hideki, Karayama, Masato, Hozumi, Hironao, Furuhashi, Kazuki, Enomoto, Noriyuki, Nakamura, Yutaro, Inui, Naoki, Ogawa, Noriyoshi, Suda, Takafumi
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.12.2019
• Subjects: Aged; Autoantibodies - immunology; Dermatomyositis - complications; Dermatomyositis - immunology; Dermatomyositis - metabolism; Female; Humans; Interferon-Induced Helicase, IFIH1 - immunology; Lectins, C-Type - metabolism; Logistic Models; Lung - metabolism; Lung - pathology; Lung Diseases, Interstitial - etiology; Lung Diseases, Interstitial - metabolism; Macrophages - metabolism; Macrophages - pathology; Male; Mannose-Binding Lectins - metabolism; Middle Aged; Prognosis; Receptors, Cell Surface - metabolism; Respiratory Insufficiency - etiology; Respiratory Insufficiency - metabolism; Respiratory Insufficiency - mortality; Retrospective Studies; CD206; dermatomyositis; interstitial lung disease; MDA5; macrophage-mannose receptor
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/kez185

Abstract 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.