title: Increased levels of neutrophil extracellular trap remnants in the circulation of patients with small vessel vasculitis, but an inverse correlation to anti-neutrophil cytoplasmic antibodies during remission.
abstract: OBJECTIVE
  Neutrophil extracellular traps (NETs) have been visualized at the site of ANCA-associated vasculitis (AAV) lesions. Increased levels of NET remnants in the circulation have been reported in some AAV patients with active disease. The aim of the present study was to analyse NET remnants in a larger cohort of AAV patients with varying degrees of disease activity and to elucidate possible factors responsible for remnant variation.
  
  
  METHODS
  Levels of NET remnants in the circulation of healthy controls (HCs; n = 31) and AAV patients (n = 93) were determined with ELISA. NET remnants were then correlated with ANCA levels, spontaneous and induced cell death (NETosis/necrosis) in vitro, neutrophil count and corticosteroid therapy.
  
  
  RESULTS
  Patients with active disease showed higher levels of circulating NET remnants compared with patients in remission (P = 0.026) and HCs (P = 0.006). From patients sampled during both remission and active disease, we found increased levels during active disease (P = 0.0010). In remission, ANCA-negative patients had higher levels of NET remnants than ANCA-positive patients and a negative correlation was observed between NET remnants and PR3-ANCA (rs = -0.287, P = 0.048). NET remnants correlated with neutrophil count in HCs (rs = 0.503, P = 0.014) but not in patients during remission. Neutrophils from patients showed enhanced spontaneous cell death (P = 0.043).
  
  
  CONCLUSIONS
  We found increased levels of circulating NET remnants in patients with active AAV. Furthermore, AAV patients exhibited an increased propensity for spontaneous cell death. NET remnant levels seem to be positively related to disease activity and neutrophil count, but inversely related to ANCA at least during remission.
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, daniel.soderberg@liu.se.
authors.forename: Daniel
authors.initials: D
authors.lastname: Söderberg
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping.
authors.forename: Tino
authors.initials: T
authors.lastname: Kurz
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping.
authors.forename: Atbin
authors.initials: A
authors.lastname: Motamedi
authors.affiliation: Department of Clinical Sciences, Section of Nephrology, Lund University, Lund.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hellmark
authors.affiliation: Department of Rheumatology, Department of Clinical and Experimental Medicine and.
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Department of Nephrology, Linköping University, Linköping, Sweden.
authors.forename: Mårten
authors.initials: M
authors.lastname: Segelmark
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000188:drug therapy*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002452:Cell Count; D002478:Cells, Cultured; D065206:Extracellular Traps / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D017830:Octoxynol / Q000494:pharmacology; D012074:Remission Induction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000305:Adrenal Cortex Hormones; D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D017830:Octoxynol; D013755:Tetradecanoylphorbol Acetate
keywords: ANCA; ANCA-associated vasculitis; NET remnants; neutrophil extracellular trap (NET); small vessel vasculitis