|
 |
|||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||
 |
 |
|
|
Is PR3-ANCA Formation Initiated in Wegener's Granulomatosis Lesions? Granulomas as Potential Lymphoid Tissue Maintaining Autoantibody Production
Department of Rheumatology, University of Lübeck, Lübeck, Germany, and Rheumaklinik Bad Bramstedt, 24576 Bad Bramstedt, Germany
Address for correspondence: Jan Voswinkel, M.D., Rheumaklinik Bad Bramstedt, Oskar Alexander Strasse 26, 24576 Bad Bramstedt, Germany. Voice: +49-41-92-902762; fax: +49-41-92-902389. voswinkel{at}rheuma-zentrum.de
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.
Key Words: Wegener's granulomatosis (WG) • granuloma • lymphoid tissue • T lymphocytes • B lymphocytes This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||
 |
 |
