Identification of biomarkers related to neutrophils and two molecular subtypes of systemic lupus erythematosus

Abstract

Abstract Background Systemic lupus erythematosus (SLE), an autoimmune disease with complex pathogenesis, poses a considerable threat to women’s health. Increasing evidence indicates that neutrophils play an important role in the development and progression of lupus. Methods Weighted correlation network analysis and single-sample gene set enrichment analysis (GSEA) were used to analyse SLE expression data from a comprehensive gene expression database and identify modules associated with neutrophils. Thereafter, the biomarkers most closely related to neutrophils were identified. We reclassified SLE into two molecular subtypes based on the aforementioned biomarkers and evaluated cell infiltration, molecular mechanisms, and signature pathways in each subtype. Results The results showed significant differences in immunological characteristics between the two molecular subtypes of SLE. Hub genes were significantly upregulated in the NEUT-H subtype, and they may be associated with lupus activity. The GSEA revealed associations between our biomarkers and key metabolic pathways. Conclusions Our study provides not only a classification for patients with SLE but also new cell and gene targets for immunotherapy, as well as a new experimental paradigm to explore immunotherapy for other autoimmune diseases.