Clinic for Rheumatology and Clinical Immunology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany.
Institute of Nutritional Medicine, University of Lübeck, Lübeck, Germany.
Respir Med. 2024 Nov-Dec;234:107825. doi: 10.1016/j.rmed.2024.107825. Epub 2024 Sep 30.
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.
高密度脂蛋白（HDL）影响内皮细胞功能，如内皮细胞黏附分子的表达，并发挥抗凋亡/抗血栓功能。因此，深入分析脂蛋白可能揭示系统性硬化症（SSc）和间质肺病（SSc-ILD）等决定死亡率的疾病表现的（微血管）病变的生物标志物。由于核磁共振（NMR）光谱提供了经典分析能力之外的广泛脂蛋白参数，因此本文使用它来检查 SSc 中的脂蛋白谱。
为了检测代谢和脂质组学谱，使用 Bruker 的体外诊断研究（IVDr）方案通过 1H NMR 光谱分析来自临床特征明确的 SSc 患者（n=100）和年龄和性别匹配的健康对照者（n=40）的血清样本。进行统计分析以验证显著发现，并搜索脂蛋白与临床表型之间的关联。
有 SSc-ILD 和肺纤维化的患者显示 HDL 水平降低。此外，载脂蛋白 A1+A2 及其 HDL 分数的减少反映了 SSc-ILD 患者的独特脂蛋白谱。这种关联独立于潜在的血脂异常临床混杂因素。值得注意的是，在 SSc-ILD 中，HDL 水平与 FVC（用力肺活量）、DLCO（一氧化碳肺扩散能力）和改良的 Rodnan 皮肤评分相关。
这些结果表明，HDL 及其脂蛋白可以被视为 SSc-ILD 的潜在新生物标志物。免疫介导的 HDL 对内皮细胞的影响促进微血管病变——这是 SSc 的病理生理学特征之一。因此，需要更密切地前瞻性评估 HDL 测定及其脂蛋白的能力，以更个体化地评估 SSc-ILD。
