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

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.

Keywords: CD206; MDA5; dermatomyositis; interstitial lung disease; macrophage-mannose receptor.