Combined plasma metabolomic and transcriptomic analysis identify histidine as a biomarker and potential contributor in SLE pathogenesis

Yukiko Iwasaki, Yusuke Takeshima, Masahiro Nakano, Mai Okubo, Mineto Ota, Akari Suzuki, Yuta Kochi, Tomohisa Okamura, Takaho Endo, Ichiro Miki, Kazuhiro Sakurada, Kazuhiko Yamamoto, Keishi Fujio

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Pages (from-to)905-913
Number of pages9
JournalRheumatology (Oxford, England)
Issue number2
Publication statusPublished - 2023 Feb 1


  • histidine
  • metabolome
  • plasmablast
  • SLE

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)


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