Introduction to Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)

GPA and MPA are two forms of systemic vasculitides, collectively known as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), that 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.1

The significant and important potential outcome of GPA and MPA is that the vasculitis can result in damage to the vessel wall leading to vessel occlusion, tissue ischemia, and localized necrosis. These all contribute to the clinical manifestations of GPA and MPA, which may involve multiple organs of the body, often including the kidneys, where it presents as microscopic hematuria, proteinuria and/or increase in serum creatinine.1-3

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

What are GPA and MPA?

GPA and MPA are systemic, autoimmune diseases that affect small- to medium-sized blood vessels5

  • Show similar focal necrotizing lesions involving arterioles, venules, and capillaries6
  • Often are associated with the serologic presence of anti-neutrophil cytoplasmic antibodies (ANCAs) against cytoplasmic proteins (proteinase 3 [PR3] and myeloperoxidase [MPO]) expressed on the surface of neutrophils6
  • Form part of the ANCA-associated category of vasculitides, although not all patients with GPA or MPA have ANCAs7
  • Often involve the kidneys6
    • Presents as microscopic hematuria, proteinuria and/or increase in serum creatinine8

GPA

  • Characterized by granulomatous inflammation of the upper and lower respiratory tract6
  • Mainly associated with ANCAs against PR36

MPA

  • Characterized by small vessel vasculitis without granulomatous inflammation6
  • Mainly associated with ANCAs against MPO6
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.9

References:

  1. Bosch X, Guilabert A, Espinosa G, Mirapeix E. Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA. 2007;298(6):655-669.
  2. Langford CA. Vasculitis. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S216-225.
  3. Gómez-Puerta JA, Bosch X. Anti-neutrophil cytoplasmic antibody pathogenesis in small-vessel vasculitis: an update. Am J Pathol. 2009;175(5):1790-1798.
  4. 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.
  5. 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.
  6. Pallan L, Savage CO, Harper L. ANCA-associated vasculitis: from bench research to novel treatments. Nat Rev Nephrol. 2009;5(5):278-286.
  7. Falk RJ, Jennette JC. ANCA disease: where is this field heading? J Am Soc Nephrol. 2010;21(5):745-752.
  8. McPherson RA, Ben-Ezra J. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd ed. Philadelphia, PA: Elsevier Saunders; 2011:445-479.
  9. Dr. J. Charles Jennette, direct communication.
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