#3830 TRAINED INNATE IMMUNITY IN RESPONSE TO NUCLEAR ANTIGENS IN SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract Background and Aims Systemic lupus erythematosus (SLE) is an autoimmune disease directed against nuclear antigens, including those derived from apoptotic microparticles (MPs) neutrophil extracellular traps (NETs). Innate immune cells display hyperreactive phenotype in patients with SLE, increased expression of immunostimulatory surface markers production proinflammatory cytokines. We hypothesize that the innate SLE caused by induction trained immunity. Trained immunity a de facto memory elicited initial stimulus induces metabolic epigenetic changes results more vigorous inflammatory response to subsequent stimuli. Here we aim investigate whether autoantigens MPs NETs can induce patients. Method To capability stimulated healthy PBMCs isolated or plasma for 24 hours, washed rested five days. Cells were restimulated lipopolysaccharide (LPS) Pam3CSK4. test activation status cells, controls different TLR agonists. Cytokine was measured using ELISA. Immune cell subsets analyzed flow cytometry. performed RNA sequencing Chromatin immunoprecipitation (ChIP) histone 3 lysine 4 trimethylation (H3K4me3) on monocytes controls. Results found vitro both NETs, as well patients, Initial stimulation MPs, resulted Tumor necrosis factor (TNF) Interleukin (IL) 6 upon restimulation Assessment circulating showed higher percentages compared controls, produce levels pro-inflammatory cytokines (IL-6, IL-1ß, TNF) after Toll-like receptor agonists, indicating This accompanied metabolism inflammation-related genes, underscoring typical cells. Epigenetic analysis revealed major H3K4me3, mark associated Conclusion Our findings provide new insight into pathogenesis showing be SLE-related antigens present demonstrating have phenotype. yields possible biomarker risk flares offers potential target developing therapeutic strategies.