Increased formation of neutrophil extracellular traps induced by autophagy and identification of autophagy‐related biomarkers in systemic lupus erythematosus

Abstract Abnormal death of neutrophils and the subsequent ineffective clearance of cell fragments result in production of autoantigens that can lead to systemic lupus erythematosus (SLE). Excessive formation of neutrophil extracellular traps (NETs) can trigger the synthesis of pro‐inflammatory cytokines such as type I interferons, leading to tissue damage and immune dysfunction in SLE patients. In this study, we found that a decrease in neutrophil counts in the peripheral blood was correlated with clinical parameters in SLE patients. Patients with low neutrophil counts had high renal activity index and chronicity index scores. NET formation and neutrophil autophagy in SLE patients were increased. The autophagy inhibitor hydroxychloroquine was shown to restrict NET formation. Using comprehensive bioinformatics analysis, we found that the expression of the autophagy‐related gene, hypoxia‐inducible factor 1A (HIF1A), was enhanced in peripheral neutrophils and in the renal glomeruli in SLE patients. Targeting HIF1A could be a potential therapeutic approach for SLE.