Metabolomic signature identifies HDL and apolipoproteins as potential biomarker for systemic sclerosis with...

High-density lipoproteins (HDL) affect endothelial functions such as the expression of endothelial cell adhesion molecules and exert anti-apoptotic/-thrombotic functionalities. Therefore, profound analysis of lipoproteins may unveil biomarkers for (micro-)vasculopathy in systemic sclerosis (SSc) and mortality determining disease manifestations like interstitial lung disease (SSc-ILD). Because nuclear magnetic resonance (NMR) spectroscopy provides a wide range of lipoprotein parameters beyond the capabilities of classical analyses it has been used herein to examine lipoprotein profiles in SSc.

To detect the metabolic and lipidomic profile serum samples from clinically well-characterized SSc patients (n = 100) and age-and sex-matched healthy controls (n = 40) were analyzed by 1H NMR spectroscopy using Bruker's in-vitro diagnostic research (IVDr) protocol. Statistical analyses were performed to validate significant findings and to search for associations between lipoproteins and clinical phenotypes.

Patients with SSc-ILD and lung fibrosis displayed reduced HDL levels. Furthermore, a reduction in apolipoprotein A1 + A2 and its HDL fractions reflected a distinct lipoprotein profile for SSc-ILD patients. This association was independent of potential clinical confounders for dyslipidemia. Notably, in SSc-ILD HDL levels correlate with FVC (forced vital capacity), DLCO (diffusion capacity of the lungs for carbon monoxide), and the modified Rodnan-Skin-Score.

These results suggest HDL and its lipoproteins may be considered as potential new biomarkers for SSc-ILD. Immune-mediated HDL effects on the endothelium facilitate microvasculopathy - one of the pathophysiological hallmarks in SSc. Therefore, a closer prospective evaluation of the capability of HDL-determination and its lipoproteins regarding a more individualized evaluation of SSc-ILD is warranted.