Is PR3-ANCA formation initiated in Wegener's granulomatosis lesions? Granulomas as potential lymphoid tissue maintaining autoantibody production

Ann N Y Acad Sci. 2005 Jun;1051:12-9. doi: 10.1196/annals.1361.042.


In Wegener's granulomatosis (WG), antiproteinase 3 (PR3) autoantibodies (PR3-ANCA) are crucial in the development of generalized vasculitis. Wegener's pathognomonic lesion, a granulomatous inflammation of the upper and lower respiratory tract, contains abundant lymphocytes and macrophages. Lymphocyte clusters in germinal center-like formation within the granulomatous lesion are frequently observed, which suggests antigen-driven B cell maturation. Wegener's autoantigen PR3, the target for autoreactive B and T cells, is expressed in granulomatous lesions. Disease progression in WG is accompanied by a profound generalized alteration of T cell differentiation with an increase of effector memory T cells (CD4(+)CD28(-)). The cytokine profile suggests an aberrant Th1-type response either to an environmental trigger and/or the autoantigen PR3 itself. Staphylococcus aureus, a risk factor for disease exacerbation, is widely present in the upper airways in WG. The Ig gene repertoire from WG lesions indicates a predominance of VH3+ B cells with affinity to PR3 as well as to the S. aureus B cell superantigen SPA. Hence, within the WG lesion, S. aureus might support the maturation of PR3-affinity B cells that enter a germinal center reaction in contact with PR3 and T cells and expand, leading to PR3-ANCA production. Thus, granulomatous lesions could represent a potential lymphoid tissue-maintaining autoantibody production rather than a simple, random leukocyte accumulation in WG.

Publication types

  • Review

MeSH terms

  • Antibodies, Antineutrophil Cytoplasmic / biosynthesis*
  • B-Lymphocytes / immunology
  • CD28 Antigens / physiology
  • Cytokines / biosynthesis
  • Granuloma / immunology*
  • Granulomatosis with Polyangiitis / immunology*
  • Granulomatosis with Polyangiitis / pathology
  • Humans
  • Lymphoid Tissue / immunology*
  • Myeloblastin
  • Serine Endopeptidases / immunology*
  • T-Lymphocytes / immunology


  • Antibodies, Antineutrophil Cytoplasmic
  • CD28 Antigens
  • Cytokines
  • Serine Endopeptidases
  • Myeloblastin