Metabolomic signature identifies HDL and apolipoproteins as potential biomarker for systemic sclerosis with interstitial lung disease

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Endothelium; HDL; Lung fibrosis; Metabolomics; Microvasculopathy; SSc-Associated interstitial lung disease (SSc-ILD).