What is ANCA-associated Vasculitis?

ANCA-associated vasculitides are systemic autoimmune diseases that affect small- to medium-sized blood vessels1

  • They show similar focal necrotizing lesions involving arterioles, venules, and capillaries2
  • They often are associated with the serologic presence of antineutrophil cytoplasmic antibodies (ANCAs) against cytoplasmic proteins (proteinase 3 [PR3] and myeloperoxidase [MPO]) expressed on the surface of neutrophils2
  • They form part of the ANCA-associated category of vasculitides, although not all patients with GPA, MPA, or EGPA have ANCAs3
  • They often affect the kidneys and the upper and lower respiratory tract2

GPA

  • Characterized by granulomatous inflammation of the upper and lower respiratory tract4
  • Mainly associated with ANCAs against PR32

MPA

  • Characterized by small vessel vasculitis without granulomatous inflammation4
  • Mainly associated with ANCAs against MPO2

EGPA

  • Characterized by granulomatous inflammation, asthma, and eosinophilia of the upper respiratory tract4
  • Mainly associated with ANCAs against MPO4
Trichrome Stain of Vasculitic Injury
Trichrome Stain of Vasculitic Injury

Vasculitis is inflammation of blood vessel walls, which can lead to vessel occlusion, tissue ischemia, and necrosis.4

Types of ANCA-associated vasculitis

There are 3 forms of ANCA-associated vasculitis.5

  • Granulomatosis with polyangiitis (GPA)
    • Formerly known as Wegener's granulomatosis
  • Microscopic polyangiitis (MPA)
  • Eosinophilic granulomatosis with polyangiitis (EGPA)
    • Formerly known as Churg-Strauss syndrome

All of these ANCA-associated vasculitides affect small- to medium-sized blood vessels and tend to be associated with the presence of autoantibodies to antigenic proteins normally present in the granules of neutrophils.5

The significant and important potential outcome of ANCA-associated vasculitis is that it can result in damage to the vessel wall leading to vessel occlusion, tissue ischemia, and localized necrosis. These damaging effects all contribute to the clinical manifestations of GPA, MPA, and EGPA and may involve multiple organs of the body.5-7

Histology of Necrotizing Arteritis
Histology of Necrotizing Arteritis

Necrotizing arteritis typically induces fibrinoid necrosis, which is characterized by accumulation of plasma proteins in injured tissue, including coagulation factors that are converted to fibrin by thrombogenic factors such as tissue factor.8

References:

  1. 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.
  2. Pallan L, Savage CO, Harper L. ANCA-associated vasculitis: from bench research to novel treatments. Nat Rev Nephrol. 2009;5(5):278-286.
  3. Falk RJ, Jennette JC. ANCA disease: where is this field heading? J Am Soc Nephrol. 2010;21(5):745-752.
  4. Langford CA. Vasculitis. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S216-225.
  5. Bosch X, Guilabert A, Espinosa G, Mirapeix E. Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA. 2007;298(6):655-669.
  6. Gota CE, Vasculitis: Introduction. The Merck Manual for Healthcare Professionals http://www.merckmanuals.com/professional/musculoskeletal_and_connective_tissue_disorders/vasculitis/overview_of_vasculitis.html?qt=red%20blood%20cell%20casts&sc=&alt=sh. 2008.
  7. Gómez-Puerta JA, Bosch X. Anti-neutrophil cytoplasmic antibody pathogenesis in small-vessel vasculitis: an update. Am J Pathol. 2009;175(5):1790-1798.
  8. Dr. J. Charles Jennette, direct communication.
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