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

Jan Voswinkel*, A. Müller, P. Lamprecht

*Corresponding author for this work
54 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAnnals of the New York Academy of Sciences
Volume1051
Pages (from-to)12-19
Number of pages8
ISSN0077-8923
DOIs
Publication statusPublished - 2005

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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