Localized Wegener’s Granulomatosis: Epidemiological, clinical and histopathological characteristics

Investigators: Peer Malte Aries, M.D. and Wolfgang L. Gross, M.D.

Location: Department of Rheumatology, University Hospital of Schleswig- Holstein, Campus Lübeck and Rheumaklinik Bad Bramstedt, Germany

Timeline: January 1, 2005 – December 31, 2005

Abstract:  The existence of different clinical phenotypes within Wegener’s granulomatosis (WG) has been recognized for several decades. So far, it is unknown why some patients remain in the early, localized phase of the disease with the predominance of granulomatous lesions of the upper and/or lower respiratory tract, whereas in most patients disease progresses to early systemic or generalized WG.

Specific aim:  The aim of this study is to examine the clinical, histological and immunological (phenotypes of leukocytes subsets, activation markers, proteinase 3-expression and Th1/Th2 cytokine profile) features of localized compared to generalized WG. We hypothesize, that a Th1-type cytokine expression in serum, together with a lower PR3 expression on T cells will help us to distinguish localized from generalized WG. These findings may help us to establish diagnosis of WG earlier, even if symptoms are restricted to the upper and/or lower respiratory tract like in localized WG.

Detection of distinguishing features of localized WG will give us the opportunity to start treatment early in the course of disease; even before major organ involvement has been established. Apart from diagnostical assistance the analysis might reveal new potential targets for a more specific and stage adopted therapy.

Funding for the proposed project will enable us to get a closer insight into the mechanisms of the initial course of the disease -also called localized WG- and give us new support in the clinical management of those patients. Early disease detection and prevention of disease progression is a major interest of the WGA. This data are essential and necessary for the following application for a larger grant funded by the Deutsche Forschungsgemeinschaft (German Research Society – the NIH equivalent in Germany) to further support.

The ultimate goal of this research is to identify immunological and histological features distinguishing the early granulomatous phase of WG from its subsequent generalized vasculitic stage. A closer understanding of the immunological characteristics distinguishing localized versus generalized WG will help us to develop a more stage related therapy that may prevent further progression to the generalized vasculitic disease.