Leucocyte membrane expression of proteinase 3 correlates with disease activity in patients with Wegener's granulomatosis

Wegener's granulomatosis (WG) is an inflammatory disorder characterized bygranulomatous inflammation and vasculitis, and is strongly associated withantineutrophil cytoplasmic antibodies (ANCA). ANCA in patients with WG aredirected against proteinase 3 (Pr3) in most of the cases. In vitro, uponneutrophil priming, ANCA antigens are expressed on the cell surface,thereby becoming available for interaction with ANCA. Subsequently, theseneutrophils become activated. Since ANCA can only interact with leucocyteswhen the ANCA antigens are present on the cell surface, we questionedwhether Pr3 is already expressed on the membranes of circulatinggranulocytes and monocytes of patients with WG, and whether Pr3 expressionis related to disease activity, so explaining the systemic nature andseverity of the disease. The expression of Pr3, and other ANCA antigens,i.e. myeloperoxidase (MPO) and human leucocyte elastase (HLE), was analysedon circulating granulocytes and monocytes by flow cytometry, using anon-activating whole-blood method. Disease activity was quantitated usingthe Birmingham Vasculitis Activity Score (BVAS). Seventeen patients withactive WG and anti-Pr3 antibodies were included in this study. Nine ofthese patients were also analysed at the time of remission. Twelve patientswith sepsis served as positive controls, and 10 healthy volunteers asnegative controls for granulocyte/monocyte activation. Pr3 expression onneutrophils was increased in patients with active WG compared to patientswith quiescent disease and healthy controls. On monocytes, no differencesin Pr3 expression were found between those groups. Furthermore, theexpression of MPO and HLE did not differ between patient groups and healthycontrols. Upon follow-up, the expression of Pr3 on neutrophils frompatients with active WG decreased when patients went into remission. Pr3expression on neutrophils correlated with the BVAS score (r = 0.40, P <0.05). In conclusion, circulating neutrophils from patients with active WGhave increased expression of Pr3. In addition, the expression of Pr3correlates with disease activity, suggesting that the availability of Pr3for interaction with ANCA plays a central role in the disease process.