Neutrophil extracellular traps and low-density granulocytes are associated with the interferon signature in systemic lupus erythematosus, but not in antiphospholipid syndrome

With great interest we read the article by Rahman et al 1 about the clinical associations and functional characteristics of low-density granulocytes (LDGs) in patients with systemic lupus erythematosus (SLE). LDGs are a subset of proinflammatory neutrophils which numbers are increased in patients with SLE as well as other rheumatic diseases including antineutrophil cytoplasmic antibody-associated vasculitis, rheumatoid arthritis and antiphospholipid syndrome (APS).2–5 LDGs are proposed to be involved in the pathogenesis of rheumatic diseases by spontaneously releasing neutrophil extracellular traps (NETs).5 6 NETs consist of web-like structures of chromatin decorated with antimicrobial and other neutrophil-derived peptides. NETs induce vascular damage,6 thrombosis7 and are a source of autoantigens5 to trigger autoimmunity and thus could contribute to the pathogenesis of autoimmune diseases. Arguably, the most important contribution of NET release to the pathogenesis of SLE is their effect on plasmacytoid dendritic cells (pDCs). In vitro, NETs trigger toll-like receptors on pDCs resulting in the production of interferon alpha (IFNα).6 8 9 In turn, IFNα primes neutrophils to release NETs8 9 resulting in a perpetuating pathogenic cycle of NET release and IFNα production. Elevated levels …