title: Complement activation in thrombotic thrombocytopenic purpura.
abstract: BACKGROUND
  Ultra-large von Willebrand factor and deficiency of its cleaving protease are important factors in the events leading to thrombotic microangiopathy; however, the mechanisms involved are only partly understood. Whereas pathological activation of the alternative complement pathway is linked to atypical hemolytic uremic syndrome, the role of complement activation in thrombotic thrombocytopenic purpura (TTP) is unknown. The aim of this study was to investigate whether signs of complement activation are characteristic of TTP.
  
  
  METHODS
  Twenty-three patients with TTP (18 women, median age 38 years) and 17 healthy controls (13 women, median age 38 years) were included. Complement parameters (C3, Factors H, I, B and total alternative pathway activity) together with complement activation fragments (C3a) or complexes (C1rs-INH, C3bBbP, sC5b9) were measured by ELISA or RID. ADAMTS13 activity and anti-ADAMTS13 inhibitory antibodies were measured by the VWF-FRET73 assay.
  
  
  RESULTS
  Increased levels of C3a, and SC5b9 were observed in TTP during acute episodes, as compared with healthy controls. Decreased complement C3 levels indicative of complement consumption occurred in 15% of acute TTP patients. Significant decrease of complement activation products C3a and SC5b9 was observed during plasma exchange (PEX). The sustained presence of anti-ADAMTS13 inhibitory antibodies in complete remission was associated with increased complement activation.
  
  
  CONCLUSIONS
  These data document in an observational study the presence of complement activation in TTP. Further investigation is needed to determine its potential pathogenetic significance.
authors.affiliation: Department of Hematology and Stem Cell Transplantation, St István and St László Hospital of Budapest, Budapest, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Réti
authors.forename: P
authors.initials: P
authors.lastname: Farkas
authors.forename: D
authors.initials: D
authors.lastname: Csuka
authors.forename: K
authors.initials: K
authors.lastname: Rázsó
authors.forename: Á
authors.initials: Á
authors.lastname: Schlammadinger
authors.forename: M L
authors.initials: ML
authors.lastname: Udvardy
authors.forename: K
authors.initials: K
authors.lastname: Madách
authors.forename: G
authors.initials: G
authors.lastname: Domján
authors.forename: C
authors.initials: C
authors.lastname: Bereczki
authors.forename: G S
authors.initials: GS
authors.lastname: Reusz
authors.forename: A J
authors.initials: AJ
authors.lastname: Szabó
authors.forename: Z
authors.initials: Z
authors.lastname: Prohászka
mesh_terms: D051722:ADAM Proteins / Q000276:immunology; D000071120:ADAMTS13 Protein; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003167:Complement Activation; D003165:Complement System Proteins / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006814:Hungary; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000276:immunology* / Q000628:therapy; D011863:Radioimmunoassay
chemical_list: D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D015415:Biomarkers; D003165:Complement System Proteins; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human