目的:在这项初步研究中,我们使用非靶向代谢组学来鉴定SLE相关性疲劳潜在潜在的生化机制或生物标志物.
方法:Metabolon使用超高效液相色谱/串联质谱法对23名患有系统性红斑狼疮(SLE)的黑人女性和21名非SLE对照的血浆样品进行了非靶向代谢组学血浆谱分析。一般疲劳的疲劳表型,身体疲劳,精神疲劳,活动减少,使用可靠且有效的多维疲劳量表(MFI)测量了动机的降低。
结果:SLE与非SLE组之间共有290种代谢物存在显着差异,包括与糖酵解有关的代谢物,TCA循环活动,血红素分解代谢,支链氨基酸,脂肪酸代谢,和类固醇。在SLE组中,控制年龄和合并症,α-酮戊二酸(AKG)和琥珀酸的TCA循环代谢产物与身体疲劳和全身疲劳有统计学意义(p<0.05)。
结论:虽然整个TCA循环中的普遍扰动被认为是疲劳的潜在机制,我们的结果表明,AKG和琥珀酸的个体代谢物可能是SLE疲劳症状治疗的潜在生物标志物或干预目标.此外,SLE组血红素代谢的扰动为促进全身性炎症的机制提供了额外的见解。
OBJECTIVE: In this pilot study, we used untargeted metabolomics to identify biochemical mechanisms or biomarkers potentially underlying SLE-related fatigue.
METHODS: Metabolon conducted untargeted metabolomic plasma profiling using ultrahigh performance liquid chromatography/tandem mass spectrometry on plasma samples of 23 Black females with systemic lupus erythematosus (SLE) and 21 no SLE controls. Fatigue phenotypes of general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation were measured with the reliable and valid Multidimensional Fatigue Inventory (MFI).
RESULTS: A total of 290 metabolites were significantly different between the SLE and no SLE groups, encompassing metabolites related to glycolysis, TCA cycle activity, heme catabolism, branched chain amino acids, fatty acid metabolism, and steroids. Within the SLE group, controlling for age and co-morbidities, TCA cycle metabolites of alpha-ketoglutarate (AKG) and succinate were statistically significantly associated (p < .05) with physical and general fatigue.
CONCLUSIONS: While pervasive perturbations in the entire TCA cycle have been implicated as a potential mechanism for fatigue, our results suggest individual metabolites of AKG and succinate may be potential biomarkers or targets of intervention for fatigue symptom management in SLE. Additionally, perturbations in heme metabolism in the SLE group provide additional insights into mechanisms that promote systemic inflammation.