title: Neutrophil-related and serum biomarkers in granulomatosis with polyangiitis support extracellular traps mechanism of the disease.
abstract: OBJECTIVE
  Granulomatosis with polyangiitis (GPA) is an autoimmune disease with still unknown etiology. Recent studies indicate that neutrophils extra-cellular traps participate in the pathophysiology of GPA. This study investigates the levels of circulating NET formation markers and neutrophil-platelet interaction in patients with GPA.
  
  
  METHODS
  We enrolled 40 GPA patients (20 in the active stage of the disease and 20 in remission). Twenty sex- and age-matched healthy subjects served as a control group. Serum/plasma levels of serine proteases, and histone-, myeloperoxidase-, proteinase-3 DNA complexes and sP-selectin were measured using ELISA or Luminex assays. Circulating platelet-neutrophil aggregates and neutrophils activation markers expression was measured by flow cytometry.
  
  
  RESULTS
  Patients in active stage of GPA had higher circulating levels of serine proteases, DNA-histone and myeloperoxidase -DNA complexes. In addition, platelet-neutrophil aggregates and sP-selectin were also elevated in this group. Platelet-neutrophil aggregates and myeloperoxidase -DNA complexes correlated positively with the disease activity score (BVAS).
  
  
  CONCLUSIONS
  NETs production and activation of platelets in GPA is supported by elevated myeloperoxidase-DNA complexes and platelet-neutrophil aggregates correlating positively with the disease activity score. This mechanism justifies laboratory measurements of myeloperoxidase-DNA complexes and plasma sP-selectin as biomarkers for studying GPA activity.
authors.affiliation: Department of Internal Medicine, and Department of Physiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Surmiak
authors.affiliation: Department of Internal Medicine, and Department of Physiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Hubalewska-Mazgaj
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wawrzycka-Adamczyk
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Szczeklik
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Musiał
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brzozowski
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland. nfsanak@cyf-kr.edu.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D065206:Extracellular Traps / Q000502:physiology*; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000502:physiology; D019007:P-Selectin / Q000097:blood; D009195:Peroxidase / Q000097:blood; D010974:Platelet Aggregation
chemical_list: D015415:Biomarkers; D019007:P-Selectin; D009195:Peroxidase