title: Neutrophil activation during attacks in patients with hereditary angioedema due to C1-inhibitor deficiency.
abstract: BACKGROUND
  Earlier studies have shown that the absolute number of neutrophil granulocytes (NGs) may increase during attack of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE). Whether NGs undergo activation during attack has not yet been investigated. However, as neutrophil elastase (NE) can cleave and inactivate C1-INH which may contribute to the dysregulation of the kallikrein-kinin system and hence, to edema formation. Our aim was to investigate the possible activation of NGs during attacks.
  
  
  METHODS
  We studied blood samples obtained from 26 patients with C1-INH-HAE during symptom-free periods and during attacks, along with samples from 26 healthy volunteers. NG count (NGC), NE, myeloperoxidase (MPO), pentraxin 3 (PTX3), CRP, C5a, factor H, IL-8, and TNF-α levels were measured.
  
  
  RESULTS
  NGC was higher during attacks than during symptom-free periods (p = 0.0132), and the same was observed for NE (p = 0.0026), MPO (p = 0.0008), and PTX3 levels (p = 0.0409). There was a strong positive correlation between NE and MPO levels during attacks (p < 0.0001, R = 0.709). Furthermore, IL-8 (p = 0.0061) and TNF-α (p = 0.0186) levels were also elevated during attacks, compared with symptom-free periods. By contrast, C5a and factor H levels were similar in samples obtained during attacks or in symptom-free periods.
  
  
  CONCLUSIONS
  Increased NGC was associated with elevated NE and MPO levels - this suggests neutrophil activation during attacks. The strong positive correlation between NE and MPO levels, together with the elevated PTX3 concentration, may indicate the expression of neutrophil extracellular traps. All these processes may contribute to the activation of kallikrein-kinin system, which leads to the onset of an edematous episode.
authors.affiliation: Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, H-1125, Budapest, Hungary. veszeli.nora88@gmail.com.
authors.forename: Nóra
authors.initials: N
authors.lastname: Veszeli
authors.affiliation: Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, H-1125, Budapest, Hungary. csuka.dorottya@med.semmelweis-univ.hu.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Csuka
authors.affiliation: Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, H-1125, Budapest, Hungary. zotter.zsuzsanna@gmail.com.|Urology Department, Medical Center, Hungarian Defence Forces, Budapest, Hungary. zotter.zsuzsanna@gmail.com.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Zotter
authors.affiliation: Central Laboratory, Kútvölgyi Clinical Block, Budapest, Hungary. imrehe@kut.sote.hu.
authors.forename: Éva
authors.initials: É
authors.lastname: Imreh
authors.affiliation: MTA-ELTE "Lendület" Complement Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary. mihaly.jozsi@freemail.hu.
authors.forename: Mihály
authors.initials: M
authors.lastname: Józsi
authors.affiliation: Haematology Unit, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. nagysz@kut.sote.hu.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Benedek
authors.affiliation: Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, H-1125, Budapest, Hungary. varga.lilian@med.semmelweis-univ.hu.
authors.forename: Lilian
authors.initials: L
authors.lastname: Varga
authors.affiliation: Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, H-1125, Budapest, Hungary. farkas.henriette@med.semmelweis-univ.hu.
authors.forename: Henriette
authors.initials: H
authors.lastname: Farkas
mesh_terms: D000328:Adult; D054179:Angioedemas, Hereditary / Q000175:diagnosis* / Q000378:metabolism*; D050718:Complement C1 Inhibitor Protein; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D018375:Neutrophil Activation / Q000502:physiology*
chemical_list: D050718:Complement C1 Inhibitor Protein; D018836:Inflammation Mediators