Molecular characterization of PANoptosis-related genes with features of immune dysregulation in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. PANoptosis is a novel form of programmed cell death involved in various inflammatory diseases. This study aimed to identify the differentially-expressed PANoptosis-related genes (PRGs) involved in immune dysregulation in SLE. Five key PRGs, including ZBP1, MEFV, LCN2, IFI27, and HSP90AB1, were identified. The prediction model with these 5 key PRGs showed a good diagnostic performance in distinguishing SLE patients from controls. These key PRGs were associated with memory B cells, neutrophils and CD8 + T cells. Besides, these key PRGs were significantly enriched in pathways involving the type I interferon responses and IL-6-JAK-STAT3 signaling. The expression levels of the key PRGs were validated in peripheral blood mononuclear cells (PBMCs) of patients with SLE. Our findings suggest that PANoptosis may be implicated in the immune dysregulation in SLE by regulating the interferons and JAK-STAT signaling pathways in memory B cells, neutrophils and CD8 + T cells.