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.

Conclusion: 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.

Figure 1

Probability of relapse-free survival by ANCA specificity (A), and by MPO-ANCA and PR3-ANCA positivity within classification groups of the Chapel Hill Consensus Conference definitions: KLD = Kidney Limited Disease (B), MPA = Microscopic Polyangiitis (C), and GPA = Granulomatosis with Polyangiitis (D).

Figure 2

Frequency of PR3- and MPO-ANCA specificity by a variety of clinical phenotypes (organ groupings are not mutually exclusive) No Lung and No ENT: Vasculitis in any organ except the lungs and the ENT system. Lung, no ENT: Vasculitis localized in the lungs but not in the ENT system. Lung*: Vasculitis localized in the lungs without indicative markers (nodules, or cavities) or histological proof (granulomas) of granulomatous inflammation. Plus Gastrointestinal (GI): Vasculitis localized at any organ plus involvement of the gastrointestinal tract. Plus Skin: Vasculitis localized at any organ plus dermal involvement. Plus Nerves: Vasculitis localized at any organ plus involvement of the nerves. Any Lung: Any type of pulmonary vasculitis such as pulmonary hemorrhage, infiltrates, nodules, cavities, granulomas, or respiratory arrest. ENT, no Lung: Vasculitis localized at the ENT system but not in the lungs. Any ENT: Any type of vasculitic manifestation of the ENT system. Lung with nodules: Vasculitis localized at the lungs with radiographic proof of nodules. Lung plus ENT: Any type of pulmonary vasculitis plus any type of vasculitic manifestation of the ENT system.