PReS-FINAL-2291: Activation of TLR pathway JSLE derived neutrophil extracellular traps

Introduction Juvenile Systemic Lupus Erythematous (JSLE) is characterised by auto-antibody production directed against nuclear auto-antigens. Toll-like receptors (TLRs) are pattern recognition receptors of the innate immune system responsible for initiating an immune response against invading pathogens. TLR 3, 7-9 have been studied in SLE due to their unique ability to detect nuclear antigen. Their expression is increased in JSLE and significantly associated with disease activity and anti-dsDNA titres. Upon recognition of an extracellular pathogen, neutrophils may release neutrophil extracellular traps (NETs) containing antimicrobial peptides to capture and neutralise pathogens. Nuclear material including DNA and histones comprise the major structural components of NETs and may act as a source of nuclear auto-antigen in SLE. The mechanism by which NETs may induce an auto-inflammatory response has not been elucidated. Our hypothesis is that neutrophil NETs are a source of nuclear auto-antigen in JSLE being detected through the TLR pathway leading to an auto-inflammatory response.