Metabolomics for Biomarker Discovery in Systemic Lupus Erythematosus

Metabolomics is the identification and quantification of the metabolome, all low-molecular-weight metabolites in a biological sample. Cell metabolism is known to have a marked impact on the function of various immune cells. We recently examined the differences in the serum metabolome between patients with systemic lupus erythematosus (SLE) and healthy subjects, using gas chromatography/mass spectrometry (GC/MS), and sought to identify candidates for metabolic biomarkers. We found that the levels of 25 metabolites were significantly different in SLE patients compared to healthy controls. A two-dimensional plot of the principal component analysis scores showed distinct clustering for the two subject groups. Multivariate analysis revealed that variations in the levels of glutamic acid, urea, tyrosine, phosphate and glycerol markedly contributed to the observed separation of metabolomic profiles of the SLE patients and healthy controls. A number of metabolites showed different changes between SLE and rheumatoid arthritis. Furthermore, the serum levels of glutamic acid were significantly correlated with the SLE disease activity index score in the patient group. These findings suggest that GC/MS-based serum metabolomics can serve as a novel diagnostic and monitoring tool for autoimmune diseases, and the pattern of variation in metabolite levels may be useful for understanding the pathophysiology of the diseases and developing novel therapeutic strategies.