Integration of multi-omics analysis reveals metabolic alterations of B lymphocytes in systemic lupus erythematosus

Objective: To link changes in the B -cell transcriptome from systemic lupus erythematosus (SLE) patients with those in their macroenvironment, including cellular and fluidic components. Methods: Analysis was performed on 363 patients and 508 controls, encompassing transcriptomics, metabolomics, and clinical data. B -cell and whole -blood transcriptomes were analysed using DESeq and GSEA. Plasma and urine metabolomics peak changes were quantified and annotated using Ceu Mass Mediator database. Common sources of variation were identified using MOFA integration analysis. Results: Cellular macroenvironment was enriched in cytokines, stress responses, lipidic synthesis/mobility pathways and nucleotide degradation. B cells shared these pathways, except nucleotide degradation diverted to nucleotide salvage pathway, and distinct glycosylation, LPA receptors and Schlafen proteins. Conclusions: B cells showed metabolic changes shared with their macroenvironment and unique changes directly or indirectly induced by IFN- alpha signalling. This study underscores the importance of understanding the interplay between B cells and their macroenvironment in SLE pathology.