Purpose of review: A breakdown of immune tolerance to self-antigens in a genetically predisposing background, precipitated by environmental triggers, contributes to the development of systemic autoimmune diseases. Renewed interest in the immunomodulatory capabilities of neutrophils in systemic autoimmunity has identified neutrophil extracellular trap (NET) formation as a distinguishing action of neutrophils in afflicted hosts.
Recent findings: Oxidation of nucleic acids and posttranslational modifications of proteins distinctly occur during NET formation and may promote enhanced immunogenicity. Various autoantibodies, immune complexes, and other inflammatory stimuli have been recently reported to promote NET formation in individuals with autoimmune diseases. Associations between level of NETosis and adverse outcomes in systemic autoimmune diseases, including thrombosis, adverse pregnancy outcomes, and renal disease, continue to be investigated.
Summary: Understanding the putative pathogenic role and sequelae of NETosis in rheumatic diseases is a major focus of ongoing research efforts. Mechanisms elucidated by these discoveries may provide novel therapeutic targets to inhibit NET formation and/or promote the clearance of immunogenic NET material.