Neutrophils- and Pyroptosis-Related Genes IL1B and PYCARD as Diagnostic Biomarkers for Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is closely associated with neutrophils and pyroptosis, but the pyroptosis related genes (PRGs) with neutrophils in SLE have been less studied. Based on public databases, key genes associated with neutrophil pyroptosis in SLE were identified through immune infiltration analysis and differential analysis. Subsequently, three machine learning algorithms were utilised to derive biomarkers. Additionally, based on the logistic regression model, we constructed a weighted score formula and determined the optimal cut-off value through receiver operating characteristic (ROC) analysis. Gene set enrichment analysis (GSEA) and localization analysis were performed on the biomarkers. The expression of the biomarkers in SLE was verified by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. Through a series of screenings, two biomarkers (PYCARD and IL1B) were obtained. The weighted score based on biomarkers could better distinguish SLE patients from healthy individuals with high diagnostic accuracy. These two biomarkers were found to be involved in the same pathways, including ‘toll-like receptor signaling pathway’, ‘NOD-like receptor signaling pathway’ and ‘chemokine signaling pathway’. Subcellular localization analyses showed that both biomarkers were mainly localised in the cytoplasm. The results of RT-qPCR and western blotting showed that PYCARD and IL1B were highly expressed in SLE samples, which was consistent with our transcriptome results. In conclusion, we filled a knowledge gap in the area of central granulocyte-associated pyroptosis in SLE. These findings provide a reference for the potential targeting of neutrophil-associated pyroptosis genes in the treatment of patients with SLE.