Antineutrophil cytoplasmic antibody-associated vasculitides and respiratory disease

Chest. 2009 Oct;136(4):1101-1111. doi: 10.1378/chest.08-3043.

Abstract

Vasculitides associated with serum positivity for antineutrophil cytoplasmic antibodies (ANCAs) are a well-established subgroup affecting small- to medium-sized vessels that are commonly recognized as ANCA-associated vasculitis, which includes necrotizing granulomatous vasculitis (NGV) [formerly Wegener granulomatosis], microscopic polyangiitis (MPA), and Churg-Strauss syndrome. NGV usually starts as a granulomatous disease of the respiratory tract and progresses to systemic disease with proteinase 3 (PR3)-ANCA-associated vasculitis, suggesting an aberrant cell-mediated immune response to exogenous or endogenous antigens in the respiratory tract and resulting in granuloma formation. In NGV, granulomata may represent lymphoid structures ultimately responsible for PR3-ANCA production. In both NGV and MPA, necrotizing glomerulonephritis and necrotizing pulmonary capillaritis may well result from an injury orchestrated by ANCA. Untreated NGV and MPA normally are rapidly progressive and fatal. Pulmonary capillaritis with alveolar hemorrhage is a severe complication in patients with MPA and NGV. Because plasma exchange removes circulating ANCAs and other proteins from the blood, its use has been advocated in critical situations of severe renal and pulmonary involvement. However, no studies of plasma exchange in ANCA-associated vasculitis focused on pulmonary involvement have been reported. Dissecting the mechanisms of inflammation may identify molecular targets for future therapies in ANCA-associated vasculitis. Thus, biological agents are emerging as potential therapies in refractory cases. Notably, rituximab and infliximab have been trialed with apparent initial clinical success.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abatacept
  • Antibodies, Antineutrophil Cytoplasmic / immunology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived
  • Humans
  • Immunoconjugates / therapeutic use
  • Immunologic Factors / therapeutic use
  • Lung Diseases / drug therapy
  • Lung Diseases / etiology*
  • Lung Diseases / mortality
  • Prognosis
  • Rituximab
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Vasculitis / immunology*

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Immunoconjugates
  • Immunologic Factors
  • Tumor Necrosis Factor-alpha
  • Rituximab
  • Abatacept