Related Experiment Video
Updated: Sep 20, 2025
From a 2DE-Gel Spot to Protein Function: Lesson Learned From HS1 in Chronic Lymphocytic Leukemia
Published on: October 19, 2014
Combined plasma metabolomic and transcriptomic analysis identify histidine as a biomarker and potential contributor
Yukiko Iwasaki1,2,3, Yusuke Takeshima1,4, Masahiro Nakano1,5
1Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo.
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.
