Abstract
Background: Vitamin D deficiency is increasingly common in systemic lupus erythematosus (SLE) patients and is associated with the disease activity and proteinuria. Recently, alterations in metabolism have been recognized as key regulators of SLE pathogenesis. Our objective was to identify changes in the serum metabolome of SLE with vitamin D deficiency.
Methods: In this study, we applied untargeted metabolomics to serum samples obtained from a cross-sectional cohort of age- and sex-matched SLE patients, with or without vitamin D deficiency. Subsequently, we performed metabolomics profiling analysis, including principal component analysis, student’s t test, fold change analysis, volcano plot analysis, cluster analysis, Spearman’s correlation analysis, KEGG enrichment analysis, regulatory network analysis and receiver operating characteristic (ROC) analysis, to identify 52 significantly altered metabolites in vitamin D deficient SLE patients. The area under the curve (AUC) from ROC analyses was calculated to assess the diagnostic potential of each candidate metabolite biomarker.
Results: Lipids accounted for 66.67% of the differential metabolites in the serum, highlighted the disruption of lipid metabolism. The 52 differential metabolites were mapped to 27 metabolic pathways, with fat digestion and absorption, as well as lipid metabolism, emerging as the most significant pathways. The AUC of (S)-Oleuropeic acid and 2-Hydroxylinolenic acid during ROC analysis were 0.867 and 0.833, respectively, indicating their promising diagnostic potential.
Conclusions: In conclusion, our results revealed vitamin D deficiency alters SLE metabolome, impacting lipid metabolism, and thrown insights into the pathogenesis and diagnosis of SLE.