title: Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis.
abstract: BACKGROUND
  The utility of antineutrophil cytoplasmic antibody (ANCA) levels to guide the management of patients with Wegener granulomatosis remains controversial.
  
  
  OBJECTIVE
  To determine whether pro-proteinase 3 (PR3)-ANCA levels are a better measure of disease activity than mature-PR3-ANCA levels, whether decreases in either level are associated with shorter time to remission, and whether increases are followed by relapse.
  
  
  METHODS
  Prospective, observational cohort study.
  
  
  METHODS
  8 United States medical centers that participated in a treatment trial for Wegener granulomatosis.
  
  
  METHODS
  156 patients with Wegener granulomatosis enrolled during periods of active disease.
  
  
  METHODS
  PR3-ANCA levels (by capture enzyme-linked immunosorbent assay) and disease activity (by the Birmingham Vasculitis Activity Score for Wegener granulomatosis).
  
  
  RESULTS
  The ANCA levels were only weakly associated with disease activity across patients. The longitudinal association within patients was stronger, but changes in ANCA levels explained less than 10% of the variation in disease activity. Decreases in mature- and pro-PR3-ANCA levels were not statistically significantly associated with shorter time to remission, and increases in mature-PR3-ANCA levels (adjusted hazard ratio, 0.8 [95% CI, 0.4 to 1.9]; P = 0.67) and pro-PR3-ANCA levels (adjusted hazard ratio, 1.0 [CI, 0.5 to 2.1]; P = 0.99) were not associated with relapse. The proportion of patients who had relapse within 1 year of an increase in PR3-ANCA levels was 40% for mature-PR3 (CI, 18% to 56%) and 43% for pro-PR3 (CI, 22% to 58%).
  
  
  CONCLUSIONS
  Samples were collected approximately every 3 months. Sensitivity and specificity of ANCA levels for detecting remission and relapse could not be calculated because each patient had different follow-up times.
  
  
  CONCLUSIONS
  Pro-PR3-ANCA is no better than mature-PR3-ANCA as a measure of Wegener granulomatosis activity. Decreases in PR3-ANCA levels are not associated with shorter time to remission, and increases are not associated with relapse. These findings suggest that ANCA levels cannot be used to guide immunosuppressive therapy.
authors.affiliation: Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Javier D
authors.initials: JD
authors.lastname: Finkielman
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.forename: Darrell
authors.initials: D
authors.lastname: Schroeder
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
authors.forename: Robert
authors.initials: R
authors.lastname: Spiera
authors.forename: E William
authors.initials: EW
authors.lastname: St Clair
authors.forename: John C
authors.initials: JC
authors.lastname: Davis
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: McCune
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Lears
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ytterberg
authors.forename: Amber M
authors.initials: AM
authors.lastname: Hummel
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Viss
authors.forename: Tobias
authors.initials: T
authors.lastname: Peikert
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
mesh_terms: D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology*; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D012680:Sensitivity and Specificity
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D053146:Myeloblastin