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

Abstract

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.

• Authors: 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
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 62 Issue 2 Pg. 905-913 (Feb 01 2023) ISSN: 1462-0332 [Electronic] England
• PMID: 35689621 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Histidine
• Biomarkers

Topics

• Animals
• Mice
• Histidine
• Transcriptome
• Metabolomics (methods)
• Biomarkers
• Lupus Erythematosus, Systemic (genetics)