ANCA-Associated Vasculitis (AAV)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare but serious autoimmune disorder that causes inflammation and damage to the small blood vessels in various organs of the body.1 Vasculitis was first reported in 1866, while granulomatosis with polyangiitis (GPA), a type of AAV formerly called Wegener’s granulomatosis, was reported by Hans Klinger in 1931. It was not until the 1980s, however, that researchers discovered how ANCAs played a role in the pathogenesis of the disease.2

Early Descriptions of ANCA-Associated Vasculitis

In 1951, Jacob Churg and Lotte Strauss reported more cases of AAV.3 By the early 1970s, there were over 250 reported cases of GPA, and the mean survival time observed for these patients was less than 6 months.2

Over the next few decades, more cases of AAV were reported, and it became clear that the disease was characterized by the presence of small vessel vasculitis and the formation of ANCAs.4

Since the discovery of ANCAs, there has been a significant increase in the diagnosis and treatment of AAV. Early use of medication to treat vasculitis, such as cyclophosphamide, has been reported. In 1978, Anthony Fauci and Sheldon Wolff made use of cyclophosphamide to treat 15 patients with GPA. Of these patients, 12 went into remission for up to 5 years.2

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The Discovery of ANCAs

In 1982, Paul Falk and his colleagues discovered that serum from patients with AAV contained antibodies that bound to the cytoplasm of neutrophils. which thereupon led to the name “antineutrophil cytoplasmic antibodies” (ANCAs). The study, published as a letter in the British Medical Journal, described the clinical course of 8 patients diagnosed with a segmental necrotising glomerulonephritis. When these patients were compared with the control of healthy individuals or patients with other autoimmune diseases, the researchers found that the ANCAs were only found in the patients with AAV.5 

In 1985, other reports from nephrologists and immunologists from Denmark and The Netherlands disclosed the presence of similar autoantibodies in 25 serum samples obtained from patients with active disease and in 4 of the 32 samples obtained from patients without active disease.6 Correspondingly, no autoantibodies were detected in the serum of 500 healthy controls and various disease controls.2

In 1988, Falk and Jennette from the University of North Carolina at Chapel Hill described histological findings that identified 2 types of autoantibodies. The first was a peripheral immunofluorescence pattern that exhibits reactivity to myeloperoxidase (MPO) on enzyme-linked immunosorbent assay (ELISA). Secondly, they found a cytoplasmic immunofluorescence pattern, which showed no reactivity to MPO on ELISA.7 In 1989, Niles and colleagues observed that a serine proteinase was responsible for the cytoplasmic pattern observed.8 

Following these observations, at the 1994 International Consensus Conference in Chapel Hill, nomenclature for the most common vasculitis entities was prepared together with a definition for each of these entities.9 However, this nomenclature was not intended to provide diagnostic criteria.10 In 2012, the created nomenclature was then revised and updated to contain more descriptive terms.11

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The Role of ANCAs in ANCA-Associated Vasculitis

Undoubtedly, the discovery of ANCAs opened new avenues for research into the pathogenesis of AAV. Various studies that were performed by Xiao and colleagues from Chapel Hill supported the pathogenic role of ANCAs in the disease.2 These studies provided evidence of the role of ANCAs, neutrophils, and complement products, particularly C5a, in the development of MPO-AAV.2

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  1. ANCA-associated vasculitis. Genetic and Rare Diseases Information Center (GARD). Updated February 2023. Accessed March 10, 2023.
  2. Carette S. Vasculitis: what have we learned in the last 50 years? J Rheumatol. 2022;49(7):848-852. doi:10.3899/jrheum.220207
  3. Churg J, Strauss L. Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. Am J Pathol. 1951;27(2):277-301.
  4. Ball GV. The history of ANCA-associated vasculitis. Rheum Dis Clin North Am. 2010;36(3):439-446. doi:10.1016/j.rdc.2010.05.004
  5. Davies DJ, Moran JE, Niall JF, Ryan GB. Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? Br Med J (Clin Res Ed). 1982;285(6342):606. doi:10.1136/bmj.285.6342.606
  6. van der Woude FJ, Rasmussen N, Lobatto S, et al. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener’s granulomatosis. Lancet. 1985;1(8426):425-429. doi:10.1016/s0140-6736(85)91147-x
  7. Falk RJ, Jennette JC. Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med. 1988;318(25):1651-1657. doi:10.1056/NEJM198806233182504
  8. Niles JL, McCluskey RT, Ahmad MF, Arnaout MA. Wegener’s granulomatosis autoantigen is a novel neutrophil serine proteinase. Blood. 1989;74(6):1888-1893. doi:10.1182/blood.V74.6.1888.1888
  9. Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides: proposal of an international consensus conference. Arthritis Rheum. 1994;37(2):187-192. doi:10.1002/art.1780370206
  10. Falk RJ, Jennette JC. ANCA disease: where is this field heading? J Am Soc Nephrol. 2010;21(5):745-752. doi:10.1681/ASN.2009121238
  11. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11. doi:10.1002/art.37715

Reviewed by Hasan Avcu, MD, on 3/13/2023.