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Pathogenesis of granulomatosis with polyangiitis and related vasculitides

Stuart M Levine, MD, FACP
Ronald J Falk, MD
Section Editors
Richard J Glassock, MD, MACP
Gerald B Appel, MD
Deputy Editor
Albert Q Lam, MD


In January 2011, the Boards of Directors of the American College of Rheumatology (ACR), the American Society of Nephrology (ASN), and the European League Against Rheumatism (EULAR) recommended that the name "Wegener's granulomatosis" be changed to "granulomatosis with polyangiitis," abbreviated as GPA [1-3]. This change reflects a plan to gradually shift from honorific eponyms to a disease-descriptive or etiology-based nomenclature.


Granulomatosis with polyangiitis, which can be abbreviated as GPA, is a complex, immune-mediated disorder in which tissue injury results from the interplay of an initiating inflammatory event and a highly specific immune response. Part of this response is directed against previously shielded epitopes of neutrophil granule proteins, leading to high-titer autoantibodies known as antineutrophil cytoplasmic antibodies (ANCA). The production of ANCA is one of the hallmarks of GPA and related forms of vasculitis. ANCA are directed against antigens present within the primary granules of neutrophils and monocytes; these antibodies produce tissue damage via interactions with primed neutrophils and endothelial cells.

ANCA are highly specific for a group of disorders associated with vascular inflammation known as the ANCA-associated vasculitides: GPA, microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss). However, the term "ANCA-associated vasculitis" may be misleading since not all patients with clinical (and even histopathologically proven) diagnoses of GPA, MPA, or EGPA have ANCA.

Approximately 85 percent of patients with GPA have ANCA, although the percentage varies according to disease phenotype (patients with limited GPA are less likely to be ANCA positive). Among patients with MPA or EGPA, the percentages of patients who are ANCA positive are in the order of 70 and 50 percent, respectively.

The most commonly identified and evaluated antigens in GPA are the following two proteins:


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Literature review current through: Sep 2016. | This topic last updated: May 13, 2014.
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