

CONCLUSIONS: Plasma His levels are a potential biomarker for SLE patients and are associated with damage accrual. We also showed that plasmablast differentiation induced by innate immune signals was dependent on His. The oxidative phosphorylation signature in plasmablasts negatively correlated with His levels. A decrease in His plasma levels correlated with damage accrual independent of prednisolone dosage and type I IFN signature. Random forest and partial least squares-discriminant analysis identified His as an effective classifier for SLE patients. RESULTS: We demonstrate that a specific amino acid combination including His can effectively distinguish between SLE patients and healthy controls. The importance of histidine (His) in plasmablast differentiation was investigated by using mouse splenic B cells. Transcriptome data was analysed using RNA-sequencing for 18 immune cell subsets. Metabolic profiles of the plasma samples were analysed using liquid chromatography-time-of-flight mass spectrometry and capillary electrophoresis-time-of-flight mass spectrometry. 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. N2 - OBJECTIVES: To investigate metabolite alterations in the plasma of SLE patients to identify novel biomarkers and provide insight into SLE pathogenesis. Published by Oxford University Press on behalf of the British Society for Rheumatology. T1 - Combined plasma metabolomic and transcriptomic analysis identify histidine as a biomarker and potential contributor in SLE pathogenesis Our data suggest the importance of His as a pathogenic metabolite in SLE pathogenesis.", Our data suggest the importance of His as a pathogenic metabolite in SLE pathogenesis.Ībstract = "OBJECTIVES: To investigate metabolite alterations in the plasma of SLE patients to identify novel biomarkers and provide insight into SLE pathogenesis. OBJECTIVES: To investigate metabolite alterations in the plasma of SLE patients to identify novel biomarkers and provide insight into SLE pathogenesis.
