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

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

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Abstract Objective To evaluate circulating levels of intercellular 6-0 igora vibrance 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).Methods 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.Results 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 valhalla axys 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.Conclusion 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.