RESULTS: We performed plasma lipidomics and used a newly developed bioinformatics tool to mine the untargeted part of the SLS plasma and brain lipidome to search for SLS biomarkers. Plasma lipidomics showed disturbed ether lipid metabolism in known lipid classes. Untargeted lipidomics of both plasma and brain (white and grey matter) uncovered two new endogenous lipid classes highly elevated in SLS. The first biomarker group were alkylphosphocholines/ethanolamines containing different lengths of alkyl-chains where some alkylphosphocholines were > 600-fold elevated in SLS plasma. The second group of biomarkers were a set of 5 features of unknown structure. Fragmentation studies suggested that they contain ubiquinol and phosphocholine and one feature was also found as a glucuronide conjugate in plasma. The plasma features were highly distinctive for SLS with levels >100-1000-fold the level in controls, if present at all. We speculate on the origin of the alkylphosphocholines/ethanolamines and the nature of the ubiquinol-containing metabolites.
CONCLUSIONS: The metabolites identified in this study represent novel endogenous lipid classes thus far unknown in humans. They represent the first plasma metabolite SLS-biomarkers and may also yield more insight into SLS pathophysiology.
结果:我们进行了血浆脂质组学,并使用了一种新开发的生物信息学工具来挖掘SLS血浆和脑脂质的非靶向部分,以搜索SLS生物标志物。血浆脂质组学显示已知脂质类别中的醚脂质代谢受到干扰。血浆和大脑(白质和灰质)的非靶向脂质组学发现了SLS中高度升高的两种新的内源性脂质类别。第一生物标志物组是含有不同长度的烷基链的烷基磷酸胆碱/乙醇胺,其中一些烷基磷酸胆碱在SLS血浆中升高>600倍。第二组生物标志物是一组未知结构的5个特征。片段化研究表明,它们含有泛醇和磷酸胆碱,并且在血浆中还发现了作为葡糖苷酸缀合物的一个特征。SLS的血浆特征非常独特,水平>对照水平的100-1000倍,如果存在的话。我们推测烷基磷酸胆碱/乙醇胺的起源和含泛醇代谢物的性质。
结论:本研究中鉴定的代谢物代表了人类迄今未知的新型内源性脂质类别。它们代表了第一个血浆代谢物SLS-生物标志物,并且还可能对SLS病理生理学产生更多了解。