College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 548# Bingwen Road, Hangzhou, Zhejiang 310053, China.
College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
Biomolecules. 2018 Oct 3;8(4):105. doi: 10.3390/biom8040105.
The pathogenesis of systemic lupus erythematosus (SLE) remains elusive. It appears that serum lipid metabolism is aberrant in SLE patients. Determination of lipid profiles in the serum of SLE patients may provide insights into the underlying mechanism(s) leading to SLE and may discover potential biomarkers for early diagnosis of SLE. This study aimed to identify and quantify the profile of serum lipids in SLE patients ( = 30) with our powerful multi-dimensional mass spectrometry-based shotgun lipidomics platform. Multivariate analysis in the form of partial least squares-discriminate analysis was performed, and the associations between the changed lipids with cytokines and SLE disease activity index (SLEDAI) were analyzed using a multiple regression method. The results of this study indicated that the composition of lipid species including diacyl phosphatidylethanolamine (dPE) (16:0/18:2, 18:0/18:2, 16:0/22:6, 18:0/20:4, and 18:0/22:6), 18:2 lysoPC (LPC), and ceramide (N22:0 and N24:1) was significantly altered in SLE patients with < 0.05 and variable importance of the projection (VIP) > 1 in partial least squares-discriminate analysis (PLS-DA). There existed significant associations between IL-10, and both 18:0/18:2 and 16:0/22:6 dPE species with < 0.0001 and predicting 85.7 and 95.8% of the variability of IL-10 levels, respectively. All the altered lipid species could obviously predict IL-10 levels with F (8, 21) = 3.729, = 0.007, and R² = 0.766. There was also a significant correlation between the SLEDAI score and 18:0/18:2 dPE ( = 0.031) with explaining 22.6% of the variability of SLEDAI score. Therefore, the panel of changed compositions of dPE and ceramide species may serve as additional biomarkers for early diagnosis and/or prognosis of SLE.
系统性红斑狼疮(SLE)的发病机制仍不清楚。似乎 SLE 患者的血清脂质代谢异常。测定 SLE 患者血清中的脂质谱可能有助于了解导致 SLE 的潜在机制,并可能发现 SLE 早期诊断的潜在生物标志物。本研究旨在利用我们强大的基于多维质谱的 shotgun 脂质组学平台,鉴定和定量 SLE 患者(n=30)的血清脂质谱。采用偏最小二乘判别分析(PLS-DA)的多元分析方法,并采用多元回归方法分析与细胞因子和 SLE 疾病活动指数(SLEDAI)相关的变化脂质。研究结果表明,包括二酰基磷脂酰乙醇胺(dPE)(16:0/18:2、18:0/18:2、16:0/22:6、18:0/20:4 和 18:0/22:6)、18:2 溶血磷脂酰胆碱(LPC)和神经酰胺(N22:0 和 N24:1)在内的脂质种类组成在 SLE 患者中发生了显著改变,差异具有统计学意义(P<0.05),且在偏最小二乘判别分析(PLS-DA)中变量重要性投影(VIP)>1。IL-10 与 18:0/18:2 和 16:0/22:6 dPE 之间存在显著相关性,差异均有统计学意义(P<0.0001),分别可解释 IL-10 水平变异性的 85.7%和 95.8%。所有改变的脂质种类均可用 F(8,21)=3.729,P=0.007 和 R²=0.766 明显预测 IL-10 水平。SLEDAI 评分与 18:0/18:2 dPE 也呈显著正相关(r=0.031,P=0.007),可解释 SLEDAI 评分变异性的 22.6%。因此,dPE 和神经酰胺种类组成的变化可能作为 SLE 早期诊断和/或预后的附加生物标志物。