Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis

Ann Intern Med. 2007 Nov 6;147(9):611-9. doi: 10.7326/0003-4819-147-9-200711060-00005.


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.

Design: Prospective, observational cohort study.

Setting: 8 United States medical centers that participated in a treatment trial for Wegener granulomatosis.

Patients: 156 patients with Wegener granulomatosis enrolled during periods of active disease.

Measurements: 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%).

Limitations: 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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibodies, Antineutrophil Cytoplasmic / blood*
  • Biomarkers / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Granulomatosis with Polyangiitis / immunology*
  • Humans
  • Male
  • Middle Aged
  • Myeloblastin / immunology*
  • Prospective Studies
  • Recurrence
  • Remission Induction
  • Sensitivity and Specificity


  • Antibodies, Antineutrophil Cytoplasmic
  • Biomarkers
  • Myeloblastin