Plasma levels of adhesion molecules are elevated in dermatomyositis-interstitial lung disease and associated with low paraoxonase-1 activity

Abstract

To evaluate circulating levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) in patients with dermatomyositis (DM) and DM associated interstitial lung disease (DM-ILD). We performed a cross-sectional study in plasma samples from DM patients and matched healthy controls. Plasma ICAM-1 and VCAM-1 (CAM) levels were measured by ELISA. The activity of paraoxonase-1 (PON1), a high density lipoprotein (HDL) associated antioxidative enzyme was measured using paraoxonase, arylesterase and lactonase assays. Association analysis was performed between clinical predictors and CAM levels. We analyzed whether CAM levels have a mediating role in the association between PON1 activity and IIM outcomes using causal mediation analysis. Plasma samples from 83 DM patients with anti-Jo1 (n = 24), MDA5 (n = 29), and TIF1gamma (n = 30) and 28 age and sex matched healthy controls were analyzed. Plasma CAM levels were significantly higher in DM patients compared to controls. CAM levels were particularly higher in anti-MDA5 + DM patients compared to other autoantibody groups and in DM-ILD compared to DM without ILD. Higher ICAM-1 levels correlated low PON1 lactonase activity as well as worse restrictive lung physiology in multivariate models. Mediation analysis showed that 54% of the effect of low lactonase on worse DLCO was mediated through ICAM-1. Plasma CAM levels were higher in DM patients compared to healthy controls, particularly in DM patients with ILD. Our analyses support a pathway of low PON1 lactonase activity representing poor HDL function with low protective capacity of microvessels allowing increased endothelial activation leading to DM and DM-ILD. • Dermatomyositis (DM) patients had higher circulating ICAM-1 and VCAM-1 levels compared to healthy controls. • Plasma CAM levels were particularly higher in anti-MDA5 + patients and in DM with interstitial lung disease (ILD). • Our results support a potential pathway in which low PON1 associates with DM and DM-ILD partly mediated by increased endothelial activation.