2025/01/01 by Grace Filbertine, Isobel Kynoch, Genna Ali Abdullah +11
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Immune cells in cancer #Metabolomics and Mass Spectrometry Studies #Neutrophil, Myeloperoxidase and Oxidative Mechanisms
paper · pdf · doi:10.1093/cei/uxaf077
crossref issued 2025/01/01 · crossref published 2025/01/01 · openalex publication_date 2025/01/01 · crossref published-print 2025/01/21 · crossref created 2025/12/06 · crossref published-online 2025/12/09 · openalex created_date 2025/12/10 · crossref deposited 2025/12/22 · crossref indexed 2026/07/29 · openalex updated_date 2026/07/30
Neutrophils contribute to systemic lupus erythematosus (SLE) pathogenesis through reactive oxygen species and neutrophil extracellular trap (NET) production, and increased apoptotic debris which causes autoantibody production and immune complex formation. These processes drive inflammation and tissue damage. The aim of this study was to perform integrated transcriptomic and metabolomic analyses comparing paediatric and adult SLE neutrophils. Adult (aSLE) and paediatric (jSLE) patient and healthy adult (HA) and juvenile (HJ) control neutrophils were subjected to RNAseq and 1H-NMR metabolomics. Univariate, multivariate and multiomics enrichment analyses were conducted in R and with ingenuity pathway analysis (IPA). Transcriptomic analysis revealed distinct gene expression profiles. Adult and juvenile SLE neutrophils were enriched for genes regulating interferon (IFN)-α/β signalling, neutrophil degranulation and NET signalling pathways (IPA, adj.P-value <0.01). Gene Ontology analysis revealed enrichment in cell cycle and interferon signalling in aSLE and angiogenesis and tissue-specific development in jSLE. Metabolomic profiling identified distinct metabolic alterations in aSLE, with a greater complexity of metabolic changes in jSLE. Multivariate PLS-DA demonstrated group discrimination, particularly in aSLE (balanced accuracy 80%, sensitivity 80%). Variable importance in the projection >1 metabolites were enriched in taurine/hypotaurine and amino acid metabolism in aSLE. Integrating transcriptomic and metabolomic data strengthened IFN-α/β signalling, neutrophil degranulation and NET signalling (adj. P < 0.001). Additional metabolic pathways uniquely down-regulated in aSLE included glutamate and glutamine metabolism, nucleotide biosynthesis and tryptophan catabolism (adj.P< 0.01). In summary, neutrophils from SLE patients, especially in jSLE, displayed complex transcriptomic and metabolic profiles, with aberrant IFN responses and neutrophil activation.