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ANCA: Methods and Clinical Significance

  • Elena CsernokEmail author
  • Antonella Radice
Chapter
Part of the Rare Diseases of the Immune System book series (RDIS)

Abstract

Antineutrophil cytoplasmic antibodies (ANCAs) detection is a well-established diagnostic approach for patients suspected of having ANCA-associated vasculitis (AAV). Such autoantibodies may also be detected in a wide range of inflammatory and infectious diseases leading to a critical reappraisal in the diagnostic significance. ANCA-associated vasculitides are a heterogeneous group of rare syndromes characterized by necrotizing inflammation of small-/medium-sized blood vessels, which are granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA). ANCAs in these diseases are almost always directed against proteinase 3 (PR3-ANCA) and myeloperoxidase (MPO-ANCA). Most laboratories worldwide use a standard indirect immunofluorescence technique (IFT) on human neutrophils to screen for ANCA, and then confirm positive IFT results with antigen-specific immunoassays for PR3-ANCA and MPO-ANCA. New guidelines for ANCA testing have been developed based on a recent European multicenter study, and according to the revised 2017 international consensus recommendations, testing for ANCA in small-vessel vasculitis can be done by PR3-ANCA and MPO-ANCA immunoassays, without the categorical need for IFT. The clinical utility of ANCA depends on the appropriate ordering of testing (the right clinical setting) and on type of assay performed. Accurate identification of all patients with AAV and the avoidance of misdiagnosis can be achieved by the use of a “gating policy” based on clinical information given to the laboratory at the time of request. This policy limits requests for ANCA testing exclusively to clinical scenarios that may suggest a diagnosis of necrotizing vasculitis. The clinical utility of serial ANCA measurements for predicting and assessing clinical relapses is under discussion, but may be informative in subsets of patients, such as patients with renal involvement or alveolar hemorrhage and in patients treated with rituximab.

The new testing strategy for ANCA in vasculitis directly identifies the ANCA target antigen (PR3-ANCA and MPO-ANCA) and has a particular value for the AAV subclassification. Indeed, new studies have shown that AAV can be classified based on ANCA serotype, since PR3-ANCA and MPO-ANCA diseases are strongly associated with distinguishable genetic alleles and different clinical and histological features. ANCA presence and the antigen specificity also may have important value as a prognostic factor and may serve as a guide for immunosuppressive therapy.

Keywords

Proteinase 3-ANCA Myeloperoxidase-ANCA Methods New recommendations Clinical significance 

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Internal Medicine, Rheumatology and Immunology, Vasculitis-Center South Tübingen-Kirchheim, Medius Klinik KirchheimAkademisches Lehrkrankenhaus der Universität TübingenKirchheim unter TeckGermany
  2. 2.Department of Microbiology and VirologySan Carlo Borromeo Hospital—ASST Santi Paolo e CarloMilanItaly

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