title: Classification of antineutrophil cytoplasmic autoantibody vasculitides: the role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis.
abstract: OBJECTIVE
  To compare the usefulness of 3 currently used classification systems in predicting the outcomes of treatment resistance, disease relapse, end-stage renal disease (ESRD), and death in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
  
  
  METHODS
  Three classification systems were applied to 502 patients with biopsy-proven AAV: 1) the Chapel Hill Consensus Conference (CHCC) definition with categories for granulomatosis with polyangiitis (GPA) (Wegener's), microscopic polyangiitis (MPA), and kidney-limited disease; 2) the European Medicines Agency (EMA) system with categories for GPA and MPA; and 3) classification based on ANCA with specificity for myeloperoxidase (MPO ANCA) versus ANCA with specificity for proteinase 3 (PR3 ANCA). Outcomes included treatment resistance, relapse, ESRD, and death. Proportional hazards models were compared between systems using an information-theoretic approach to rank models by predictive fit. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) and P values are reported.
  
  
  RESULTS
  ANCA specificity was predictive of relapse, with PR3 ANCA-positive patients almost twice as likely to relapse as those with MPO ANCA (HR 1.89 [95% CI 1.33-2.69], P = 0.0004), and ANCA specificity had the best predictive model fit (model rank 1) compared to the CHCC and EMA systems. The CHCC and EMA systems did not predict relapse. By ANCA specificity, categories of GPA, MPA, and kidney-limited disease did not distinguish differences in probability of relapse-free survival. None of the systems predicted treatment resistance, ESRD, or death.
  
  
  CONCLUSIONS
  ANCA specificity independently predicts relapse among patients with AAV with renal disease. Classification and diagnostic systems that incorporate ANCA specificity, such as PR3 ANCA-positive MPA and MPO ANCA-positive MPA, provide a more useful tool than the clinical pathologic category alone for predicting relapse.
authors.affiliation: University of North Carolina, Chapel Hill, NC 27599, USA. sofia_lionaki@med.unc.edu
authors.forename: Sophia
authors.initials: S
authors.lastname: Lionaki
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Blyth
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hogan
authors.forename: Yichun
authors.initials: Y
authors.lastname: Hu
authors.forename: Brent A
authors.initials: BA
authors.lastname: Senior
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Jennette
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Nachman
authors.forename: J Charles
authors.initials: JC
authors.lastname: Jennette
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Falk
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000145:classification* / Q000175:diagnosis / Q000276:immunology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D000918:Antibody Specificity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology*; D009195:Peroxidase / Q000276:immunology*; D011379:Prognosis
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D009195:Peroxidase; D053146:Myeloblastin