TY - JOUR
T1 - Metabolomic signature identifies HDL and apolipoproteins as potential biomarker for systemic sclerosis with interstitial lung disease
AU - Jendrek, Sebastian T.
AU - Schmelter, Franziska
AU - Schinke, Susanne
AU - Hackel, Alexander
AU - Graßhoff, Hanna
AU - Lamprecht, Peter
AU - Humrich, Jens Y.
AU - Sina, Christian
AU - Müller, Antje
AU - Günther, Ulrich
AU - Riemekasten, Gabriela
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/11/1
Y1 - 2024/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85205429544&partnerID=8YFLogxK
U2 - 10.1016/j.rmed.2024.107825
DO - 10.1016/j.rmed.2024.107825
M3 - Journal articles
C2 - 39357678
AN - SCOPUS:85205429544
SN - 0954-6111
VL - 234
JO - Respiratory Medicine
JF - Respiratory Medicine
M1 - 107825
ER -
