Morphologic spectrum of granulomatous lesions

• Vol 7 • December 2005 768 A key question for understanding chronic inflammatory and autoimmune diseases is where the disease actually begins. Wegener’s granulomatosis is a potentially life-threatening chronic inflammatory disease of as yet unknown etiology, characterized by granuloma formation, vasculitis, and an autoimmune response to “Wegener’s autoantigen“ proteinase 3, a 29 kD neutrophiland monocyte-derived serine protease [1,2]. Antineutrophil cytoplasmic autoantibodies specific for proteinase 3 are detected in about 95% of patients with generalized WG, but only in about half of those presenting with early localized WG restricted to the respiratory tract. Apart from their diagnostic value and correlation with disease activity, PR3-ANCA play a direct pathogenic role in inducing systemic vasculitis by interacting with PR3 on the surface of cytokine primed neutrophil granulocytes, as suggested by numerous in vitro and several in vivo studies. The interaction of ANCA and neutrophils results in premature neutrophil activation, subsequent endothelial cell damage, and further leukocyte recruitment [reviewed in 2]. However, it is not clear whether PR3-ANCA give rise to pathogenic granulomatous inflammation – a defining feature of WG. Instead, there is increasing evidence that WG may start as granulomatous disease in the respiratory tract and ANCA vasculitis may develop subsequently [2,3]. Moreover, WG relapses are related to granuloma formation and persistence of granulomata [2]. In this article, we review current clinical and experimental data on aspects of the “granulomatous side” of WG.