Clinical significance of soluble CD163 in polymyositis-related or dermatomyositis-related interstitial lung disease

Abstract

BackgroundMacrophage activation is involved in the pathogenesis of polymyositis (PM)/dermatomyositis (DM). CD163, a scavenger receptor expressed on the surface of activated macrophages, mediates anti-inflammatory functions. This study aimed to evaluate the clinical significance of soluble CD163 (sCD163) in PM/DM-related interstitial lung disease (ILD).MethodsThe main subjects were 48 patients with PM/DM-related ILD. As controls, 10 patients with PM/DM without ILD and 20 healthy volunteers were enrolled. In patients with PM/DM-related ILD, the baseline characteristics and clinical course were obtained through a review of patient medical records. Serum sCD163 levels at ILD diagnosis were quantified by enzyme-linked immunosorbent assay, which were compared with the other baseline clinical factors and evaluated for potential as a prognostic biomarker. In addition, immunohistochemistry analysis using anti-human CD163 antibody was performed on the lung sections of two patients with DM-related ILD (a survivor and non-survivor, respectively) and one patient with early-stage lung cancer as a normal control.ResultsThe median value of serum sCD163 in patients with PM/DM-related ILD was 818 ng/mL, which was higher than that of PM/DM patients without ILD and healthy volunteers (716 ng/mL and 340 ng/mL, respectively). Significant but mild correlations with serum sCD163 levels were observed for serum C-reactive protein levels (r = 0.322) and % predicted forced vital capacity (r = −0.301) in patients with PM/DM-related ILD. A Cox proportional hazard model demonstrated that patients with PM/DM-related ILD and higher sCD163 levels had worse prognosis (age-adjusted and gender-adjusted hazard ratio per 100 ng/mL increase 1.27, 95% confidence interval 1.11–1.45, P <0.001). In immunohistochemistry analysis, compared with normal lung, alveolar infiltration of CD163-positive macrophages was evident in the lungs of patients with DM-related ILD. Especially, the finding was more severe in the non-survivor’s lung.ConclusionsSerum sCD163 might be a potential biomarker for predicting the severity and prognosis of PM/DM-related ILD. Our results suggest the importance of macrophage activation in the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1214-8) contains supplementary material, which is available to authorized users.

A high level of serum neopterin is associated with rapidly progressive interstitial lung disease and reduced survival in dermatomyositis

“…Enomoto et al revealed that patients with higher serum sCD163 (a marker of macrophage activation) had significantly lower survival rates that those with lower sCD163. Alveolar infiltration of CD163‐positive macrophages was evident in lungs of patients with DM‐related ILD, and was particularly more severe in the non‐survivors’ lungs . Our findings indicate not only serum neopterin as a possible prognostic biomarker for DM, but also the potential role of activated macrophages in the immunopathogenesis of DM.…”

“…In a previous study, we found significantly increased serum levels of soluble CD163 (sCD163) in polymyositis and DM patients, and patients with high serum sCD163 levels also showed a higher incidence of CD163 + macrophage infiltration in muscle tissue [39]. The elevated serum sCD163 levels were further confirmed in two independent Japanese cohorts [40,41]. Enomoto et al revealed that patients with higher serum sCD163 (a marker of macrophage activation) had significantly lower survival rates that those with lower sCD163.…”

A circulating cell population showing both M1 and M2 monocyte/macrophage surface markers characterizes systemic sclerosis patients with lung involvement

“…Intriguingly, imbalance in macrophage phenotype features and macrophage activation have been lately considered essential for the development of inflammatory-autoimmune, fibrotic, infective and neoplastic disorders characterized by lung involvement [ 11 – 16 ]. Macrophages have been initially categorized as classically (M1) or alternatively activated (M2), mirroring T cells categories.…”

AST/ALT ratio as a predictor of mortality and future exacerbations of PM/DM-ILD——a retrospective cohort study with 522 cases

“…showed that higher soluble CD163 levels were associated with worse prognosis and forced volume vital percentage of predicted value. [39] Additionally, the measurement of several serum biomarkers,…”