Integrated Metabolomics and Transcriptomics Analyses Reveal Metabolic Changes in Primary Angiitis of the Central...

Metabolic characterization of primary angiitis of the central nervous system (PACNS) is crucial for understanding the disease pathogenesis and progression mechanisms, but it has not been reported in patients. This study aimed to explore changes in the plasma metabolome during the active and remission phases of PACNS and identify potential biomarkers.

We collected plasma samples from 35 patients with PACNS during the active and remission phases and 22 samples from patients with non-inflammatory disease as controls. Liquid and gas chromatography-mass spectrometry were used to analyze 63 plasma samples from 57 patients metabolically. Meanwhile, we cross-validated the metabolomics results with brain tissue transcriptomic data from comprehensive gene expression databases, enhancing the reliability of our conclusions.

A total of 3,233 metabolites were identified. Enrichment analysis showed significant changes in lactate/amino acid/glycerol-pyruvic-tricarboxylic acid, glycerophospholipid/sphingolipid-membrane metabolism, lysine/tryptophan-essential amino acid metabolism, and uracil metabolism pathways during the active phase of PACNS. These findings were confirmed in both the remission phase of PACNS patients and the transcriptomic samples. Meanwhile, metabolic abnormalities in patients with PACNS were observed with benzoxazole, sesquiterpenoid, and octyl-phenolic products, and enrichment of environmental pollutants and their estrogen-like effects. Twelve metabolites, including D-Ribose, 13s-HPODE, and C16 Sphinganine, showed potential diagnostic and therapeutic evaluation value.

Our study identified potential biomarkers and metabolic characteristics of PACNS using integrated metabolomics and transcriptomics approaches. These findings highlight the importance of understanding PACNS from a metabolic perspective and guide future diagnostic and therapeutic strategies.