Compromised clearance and persistent exposure of DNA together with the associated histones in susceptible individuals enforces autoantigen presentation and leads to expansion of autoreactive lymphocyte clones and consequent autoantibody production as exemplified in lupus.57, 58, 59 Based on our findings, we also propose that in analogy to protein cross-link formation in apoptosis60, 61 NET-specific cross-links could prevent spreading of neutrophil intracellular contents and limit harmful release of proteins (histones, NE, MPO) as well as genomic DNA into the circulation. Here, MPO is linked to systemic lupus erythematosus.