Wegener's granulomatosis

Herz. 2004 Feb;29(1):47-56. doi: 10.1007/s00059-004-2525-0.


Wegener's granulomatosis is an organ- and/or life-threatening autoimmune disease of as yet unknown etiology. The classic clinical triad consists of necrotizing granulomatous inflammation of the upper and/or lower respiratory tract, necrotizing glomerulonephritis, and an autoimmune necrotizing systemic vasculitis affecting predominantly small vessels. The detection of antineutrophil cytoplasmic antibodies directed against proteinase 3 (PR3-ANCA) is highly specific for Wegener's granulomatosis. ANCA positivity is found only in about 50% of the patients with localized Wegener's granulomatosis (which is restricted to the respiratory tract and affects < or = 5% of the patients), whereas PR3-ANCA positivity is seen in 95% of the patients with generalized Wegener's granulomatosis. Studies showing an expansion of circulating tumor necrosis factor-(TNF-)alpha-producing Th1-type CD4(+)CD28(-) T-cell effector memory T-cells and their presence as Th1-type cytokine profile- driving cell population within granulomatous lesions provide the rationale for using TNF-alpha-blocking agents in Wegener's granulomatosis refractory to standard induction therapy with cyclophosphamide and corticosteroids ("Fauci's scheme"). Vasculitis is an independent risk factor for diffuse endothelial dysfunction and may be a consequence of TNF-alpha action on endothelial cells. Recently, another study has shown intima-media thickening of the wall of the common carotid artery and bulb, as well as a significantly increased incidence of stroke, myocardial infarction and occlusive artery disease in Wegener's granulomatosis. This study suggests that systemic inflammation and vasculitis contribute to accelerated arteriosclerosis in Wegener's granulomatosis.

Publication types

  • Review

MeSH terms

  • Antibodies, Antineutrophil Cytoplasmic / blood
  • Arterial Occlusive Diseases / diagnosis*
  • Arterial Occlusive Diseases / drug therapy
  • Arterial Occlusive Diseases / immunology
  • Disease Progression
  • Granulomatosis with Polyangiitis / diagnosis*
  • Granulomatosis with Polyangiitis / drug therapy
  • Granulomatosis with Polyangiitis / immunology
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Myeloblastin
  • Phosphoproteins
  • Polyarteritis Nodosa / diagnosis*
  • Polyarteritis Nodosa / drug therapy
  • Polyarteritis Nodosa / immunology
  • Serine Endopeptidases / immunology
  • Th1 Cells / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism
  • Viral Matrix Proteins


  • Antibodies, Antineutrophil Cytoplasmic
  • Immunosuppressive Agents
  • Phosphoproteins
  • Tumor Necrosis Factor-alpha
  • Viral Matrix Proteins
  • pp150 protein, Cytomegalovirus
  • Serine Endopeptidases
  • Myeloblastin