title: Elevated plasma neutrophil elastase concentration is associated with disease activity in patients with thrombotic thrombocytopenic purpura.
abstract: BACKGROUND
  Genetic and autoimmune risk factors contribute to the development of thrombotic thrombocytopenic purpura (TTP) but triggers are needed to bring about acute disease. The aim of the study was to investigate the association of neutrophil activation with acute TTP, to assess whether neutrophil activation changes during plasma exchange therapy and to show if complement- and neutrophil activation are parallel, characteristic processes in acute TTP.
  
  
  METHODS
  Altogether 49 EDTA-plasma samples of 21 TTP patients with acute disease and 17 in remission were investigated along with 20 healthy controls. A stable complex of PMNE-proteinase-inhibitor was measured by ELISA (Calbiochem, Merck-Millipore, Darmstadt, Germany).
  
  
  RESULTS
  Acute disease was associated with significantly increased PMNE levels, the group medians were similarly low in TTP patients in remission and in healthy controls. Increased PMNE levels were characteristic for hematologically active and ADAMTS13 deficient form of TTP. PMNE concentration inversely correlated to disease activity markers platelet count (r=-0.349, p=0.032) and hemoglobin levels (p=-0.382 p=0.018). Achievement of remission was associated with significant reduction of plasma PMNE levels (p=0.031, Wilcoxon test). There was positive correlation between PMNE levels and complement activation markers C3a and Bb.
  
  
  CONCLUSIONS
  We report increased PMNE levels in acute TTP and showed its association to activity markers of acute TTP and complement activation. Effective treatment of an acute TTP episode resulted in marked decrease in PMNE levels. Our data support and extend previous observations that neutrophil extracellular traps may be released in acute TTP and potentially contribute to the pathophysiology of this disease.
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Mikes
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Sinkovits
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Farkas
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Csuka
authors.affiliation: 2nd Department of Internal Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Agota
authors.initials: A
authors.lastname: Schlammadinger
authors.affiliation: 2nd Department of Internal Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Rázsó
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Budapest.
authors.forename: Judit
authors.initials: J
authors.lastname: Demeter
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Budapest.
authors.forename: Gyula
authors.initials: G
authors.lastname: Domján
authors.affiliation: Department of Hematology and Stem Cell Transplantation, St István and St László Hospital, Budapest.
authors.forename: Marienn
authors.initials: M
authors.lastname: Réti
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. Electronic address: prohoz@kut.sote.hu.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000201:enzymology*; D055815:Young Adult
chemical_list: D019272:Leukocyte Elastase
keywords: Polymorphonuclear leukocyte; complement activation; disease activity; elastase; neutrophil granulocyte; thrombotic thrombocytopenic purpura