title: Measurement and prevalence of circulating ADAMTS13-specific immune complexes in autoimmune thrombotic thrombocytopenic purpura.
abstract: BACKGROUND
  The formation of ADAMTS13-specific circulating immune complexes (CICs) may be a pathophysiologic mechanism in autoimmune thrombotic thrombocytopenic purpura (TTP), but has not been systematically investigated.
  
  
  OBJECTIVE
  (a) To develop an assay for ADAMTS13-specific CICs; (b) to evaluate their prevalence in autoimmune TTP; and (c) to assess their association with ADAMTS13-related measurements and clinical features in autoimmune TTP patients.
  
  
  METHODS
  We developed and validated an ELISA method for ADAMTS13-specific CICs. ADAMTS13-specific CICs were searched for in 55 patients with autoimmune TTP from the Milan TTP Registry (URL:http://www.ttpdatabase.org/) and 28 controls. The associations between ADAMTS13-specific CIC levels and ADAMTS13 activity, antigen, anti-ADAMTS13 IgGs and acute TTP clinical features were assessed by multivariate linear regression.
  
  
  RESULTS
  Intra- and inter-assay coefficients of variation of the new test were 5.3 and 9.6%. In 36 patients with severe ADAMTS13 deficiency and anti-ADAMTS13 autoantibodies, the prevalence of ADAMTS13-specific CICs was 47% (n = 17; 95% confidence interval [CI], 32-63%). ADAMTS13-specific CICs were detected also in seven of 19 (37%; 95% CI, 19-59%) patients with reduced ADAMTS13 activity, but apparently negative anti-ADAMTS13 autoantibodies. ADAMTS13-specific CICs were not associated with ADAMTS13 activity, antigen or anti-ADAMTS13 IgGs. In patients with acute TTP, increasing levels of ADAMTS13-specific CICs were associated with a higher number of plasma-exchange procedures required to attain remission (per 0.1 increase in normalized OD values, beta, 2.9; 95% CI, -0.7 to 6.5).
  
  
  CONCLUSIONS
  Approximately one to two-thirds of patients with autoimmune TTP display ADAMTS13-specific CICs. A thorough investigation of the prognostic relevance of ADAMTS13-specific CIC levels in autoimmune TTP is warranted.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Fondazione Luigi Villa and Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: L A
authors.initials: LA
authors.lastname: Lotta
authors.forename: C
authors.initials: C
authors.lastname: Valsecchi
authors.forename: S
authors.initials: S
authors.lastname: Pontiggia
authors.forename: I
authors.initials: I
authors.lastname: Mancini
authors.forename: A
authors.initials: A
authors.lastname: Cannavò
authors.forename: A
authors.initials: A
authors.lastname: Artoni
authors.forename: D
authors.initials: D
authors.lastname: Mikovic
authors.forename: G
authors.initials: G
authors.lastname: Meloni
authors.forename: F
authors.initials: F
authors.lastname: Peyvandi
mesh_terms: D051722:ADAM Proteins / Q000097:blood* / Q000276:immunology; D000071120:ADAMTS13 Protein; D000328:Adult; D000936:Antigen-Antibody Complex / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015995:Prevalence; D011379:Prognosis; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood*; D012042:Registries; D015203:Reproducibility of Results; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13 protein, human; ELISA; immune complexes; thrombotic thrombocytopenic purpura; von Willebrand factor