Antineutrophil cytoplasmatic autoantibodies with specificity to proteinase 3

Antineutrophil cytoplasmatic autoantibodies (ANCA) with specificity to Proteinase 3 (PR3-ANCA) are serological marker for Wegener's granulomatosis (WG) and are involved in the pathophysiology of the associated vasculitis. PR3 is a neutral serine protease that is localized in the cytoplasmic granules of neutrophils and the lysosomes of monocytes. Priming and apoptosis of neutrophils results in an increased expression of the membrane bound PR3, making them accessible for ANCA. In vitro studies have shown that simultaneous binding of ANCA to PR3 and Fc-RII receptors expressed on the cell surface of previously primed neutrophils causes degranulation and an oxidative burst of the neutrophils. Additionally, recently it was demonstrated that ANCA generated against murine PR3 had significant pro-inflammatory effects in wild-type mice, but did not induce a vasculitic disease reminiscent of human ANCA-associated vasculitis. In the clinical setting, the proof of PR3-ANCA is a strong indication for WG but per se does not allow the diagnosis of WG. The sensitivity of ANCA testing is related to the extent, severity, and activity of disease at the time of sampling. The best diagnostic performance is obtained when immunofluorescence (IIF) is combined with PR3-ANCA ELISA (the diagnostic sensitivity and specificity increased up to 73 and 99%, respectively). Even when there is a good correlation between PR3-ANCA ELISA levels and disease activity during the course of the disease, changes cannot be only the basis for therapeutical decisions.