UCLA

Purpose: Damage to the vascular endothelium is strongly implicated in the pathogenesis of idiopathic inflammatory myopathies (IIM). Normal high density lipoprotein (HDL) protects the vascular endothelium from damage from oxidized phospholipids, which accumulate under conditions of oxidative stress. The current work evaluated the function of HDL in IIM patients.

Methods: HDL’s anti-oxidant function was measured in IIM patients using a cell free assay, which assesses the ability of isolated patient HDL to inhibit oxidation of low density lipoproteins (LDL). Cholesterol profiles were measured for all patients and subgroup analysis included assessment of oxidized fatty acids in HDL by mass spectrometry and plasma myeloperoxidase (MPO) activity. A subgroup of IIM patients were compared to a group of healthy controls (HC).

Results: HDL was dysfunctional in patients with IIM compared to HC and associated with higher plasma MPO activity and higher oxidized fatty acids in HDL. Higher 5-HETE in HDL correlated with impaired lung diffusion capacity in patients with interstitial lung disease, and HDL function was most impaired in patients with MDA5 or anti-synthetase antibodies. In multivariate analysis including 182 IIM patients, dysfunctional HDL was associated with higher disease activity and DM diagnosis.

Conclusions: The anti-oxidant function of HDL is abnormal in IIM patients and may warrant further investigation for its role in propagating microvascular inflammation and damage in this patient population.