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  • Review Article
  • Published:

ANCA-associated vasculitis — clinical utility of using ANCA specificity to classify patients

Nature Reviews Rheumatology volume 12, pages 570–579 (2016)Cite this article

Subjects

Key Points

  • Anti-neutrophil cytoplasmic antibodies (ANCAs) specific for leukocyte proteinase 3 and myeloperoxidase — PR3-ANCAs and MPO-ANCAs, respectively — define distinct conditions among patients with ANCA-associated vasculitides (AAV)

  • Classification of patients with small-vessel vasculitis based on ANCA specificity is feasible and could provide timely and clinically relevant diagnostic information more readily than clinical syndromes based on current classification systems

  • Patients with PR3-AAV and MPO-AAV do not share the same genetic background and have only some pathophysiologic mechanisms in common

  • ANCA specificity predicts response to induction therapies: rituximab is more effective than cyclophosphamide in patients with PR3-AAV (by contrast, both treatments are similarly effective in patients with MPO-AAV)

  • ANCA specificity predicts differences in long-term prognosis: patients with PR3-ANCAs are at higher risk of relapse than patients with MPO-ANCAs

  • Future studies should evaluate whether the duration of immunosuppressive maintenance therapy should be different for patients with PR3-AAV versus those with MPO-AAV after remission induction

Abstract

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a heterogeneous group of rare syndromes characterized by necrotizing inflammation of small and medium-sized blood vessels and the presence of ANCAs. Several clinicopathological classification systems exist that aim to define homogeneous groups among patients with AAV, the main syndromes being microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). Two main types of ANCA can be detected in patients with AAV. These ANCAs are defined according to their autoantigen target, namely leukocyte proteinase 3 (PR3) and myeloperoxidase (MPO). Patients with GPA are predominantly PR3-ANCA-positive, whereas those with MPA are predominantly MPO-ANCA-positive, although ANCA specificity overlaps only partially with these clinical syndromes. Accumulating evidence suggests that ANCA specificity could be better than clinical diagnosis for defining homogeneous groups of patients, as PR3-ANCA and MPO-ANCA are associated with different genetic backgrounds and epidemiology. ANCA specificity affects the phenotype of clinical disease, as well as the patient's initial response to remission-inducing therapy, relapse risk and long-term prognosis. Thus, the classification of AAV by ANCA specificity rather than by clinical diagnosis could convey clinically useful information at the time of diagnosis.

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Figure 1: Differences between PR3 and MPO and their respective ANCAs.
Figure 2: PR3-ANCAs and MPO-ANCAs in clinical studies.

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Acknowledgements

This work was supported by grants from the French Society of Rheumatology (D.C.) and the American Society of Nephrology (E.C.-L.G.).

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Thoracic Disease Research Unit, Mayo Clinic, 200 First Street, Rochester, 55905, Minnesota, USA

    Divi Cornec & Ulrich Specks

  2. European University of Brittany and Brest University Hospital, Boulevard Tanguy Prigent, Brest, 29609, France

    Divi Cornec & Emilie Cornec-Le Gall

  3. Division of Nephrology, Mayo Clinic, 200 First Street, Rochester, 55905, Minnesota, USA

    Emilie Cornec-Le Gall & Fernando C. Fervenza

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  1. Divi Cornec
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  2. Emilie Cornec-Le Gall
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D.C. and E.C.-L.G. researched the data and contributed equally to writing the article. All authors provided a substantial contribution to discussions of the content and contributed equally to review and/or editing of the manuscript before submission.

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Correspondence to Ulrich Specks.

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Cornec, D., Gall, EL., Fervenza, F. et al. ANCA-associated vasculitis — clinical utility of using ANCA specificity to classify patients. Nat Rev Rheumatol 12, 570–579 (2016). https://doi.org/10.1038/nrrheum.2016.123

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