Combined plasma metabolomic and transcriptomic analysis identify histidine as a biomarker and potential contributor in SLE pathogenesis
Combined plasma metabolomic and transcriptomic analysis identify histidine as a biomarker and potential contributor in SLE pathogenesis
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DOI：
10.1093/rheumatology/keac338
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发表时间：
2022-02-24
期刊：
影响因子：
5.5
通讯作者：
Fujio, Keishi
中科院分区：
文献类型：
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作者：
Iwasaki, Yukiko;Takeshima, Yusuke;Fujio, Keishi
目的研究系统性红斑狼疮（SLE）患者血浆中代谢物的变化，寻找新的生物标志物，为阐明SLE的发病机制提供依据。方法收集SLE患者41例（发现队列）和37例（重复队列），健康对照组30例和29例，RA患者19例（疾病对照组）。采用液相色谱-飞行时间质谱法和毛细管电泳-飞行时间质谱法分析血浆样品的代谢特征。使用RNA测序分析18个免疫细胞亚群的转录组数据。用小鼠脾B细胞研究了组氨酸（His）在浆母细胞分化中的重要性。结果我们证明了包括His在内的特定氨基酸组合可以有效区分SLE患者和健康对照。随机森林和偏最小二乘判别分析确定了他作为一个有效的分类系统性红斑狼疮患者。His血浆水平的降低与损伤累积相关，与泼尼松龙剂量和I型IFN特征无关。浆母细胞中的氧化磷酸化特征与His水平呈负相关。我们还发现，由先天免疫信号诱导的浆母细胞分化依赖于His。结论血浆His水平是SLE患者的潜在生物标志物，并与损害的发生有关。我们的数据表明，作为一种致病代谢产物在SLE发病机制的重要性。
Objectives To investigate metabolite alterations in the plasma of SLE patients to identify novel biomarkers and provide insight into SLE pathogenesis. Methods Patients with SLE (n = 41, discovery cohort and n = 37, replication cohort), healthy controls (n = 30 and n = 29) and patients with RA (n = 19, disease control) were recruited. Metabolic profiles of the plasma samples were analysed using liquid chromatography-time-of-flight mass spectrometry and capillary electrophoresis-time-of-flight mass spectrometry. Transcriptome data was analysed using RNA-sequencing for 18 immune cell subsets. The importance of histidine (His) in plasmablast differentiation was investigated by using mouse splenic B cells. Results We demonstrate that a specific amino acid combination including His can effectively distinguish between SLE patients and healthy controls. Random forest and partial least squares-discriminant analysis identified His as an effective classifier for SLE patients. A decrease in His plasma levels correlated with damage accrual independent of prednisolone dosage and type I IFN signature. The oxidative phosphorylation signature in plasmablasts negatively correlated with His levels. We also showed that plasmablast differentiation induced by innate immune signals was dependent on His. Conclusions Plasma His levels are a potential biomarker for SLE patients and are associated with damage accrual. Our data suggest the importance of His as a pathogenic metabolite in SLE pathogenesis.