Some aspects of Wegener's granulomatosis

Wegener`s granulomatosis (WG) is a granulomatous and vasculitic disease of unknown origin. It follows a biphasic course and its classic triad involves upper respiratory tract, lung and renal disease which is also called systemic or vasculitic WG. The pathological hallmarks are the vasculitis and granuloma. The serological hallmark is an antibody directed against neutrophil proteinase 3 (PR3-ANCA or cANCA). In systemic WG the cANCA can be found in up to 100% of patients.

The limited variant, also called initial, localized or granulomatous phase, is a syndrom without renal or systemic (vascular) involvement. Only about half of the patients with limited WG are positive for cANCA. T-cell and cytokines investigations show a characteristic T-helper cell-1 (Th1) profil in the granulomatous, and a Th2 profile in the vasculitic phase.

These results support the hypothesis that the two-phases of WG are maintained by polarized T cell subpopulations and a switch in polarization may explain the transition from the granulomatous to the vasculitic phase.

The etiology of WG is still unknown. It has been speculated that the phenotypes might be a consequence of various exogenous and endogenous factors, which activate the immunresponse leading to tissue destruction. Although WG seems to affect predominantly Caucasians, the genetic factors involved are unknown. Gene polymorphisms (PMs) are known to influence phenotypes of numerous diseases and some cytokines genes PMs are suspected to modify the course of granulomatous disorders, like WG. PMs of these cytokine genes might cause in an altered transcription rate which would finally lead to genetically determined high or low producers with the consequence of imbalances in their cytokine network with possible relevance for the immunopathological mechanisms of WG.