Proteinase 3 (PR3; non recombinant)

Cat. No.Available inproduct_image_56
186000.1 mg
186011.0 mg
 


Diseases:
Wegener's Granulomatosis

Proteinase 3 (PR3) is a neutral serine protease stored in the azurophilic neutrophilic granulocytes, consisting of 228 amino acids (MW 29-33 kDa depending on glycoform). It has substantial sequence homology with neutrophil elastase, cathepsin G and azurocidin. The primary function of these neutrophil-derived serine proteases is thought to be degradation of extracellular proteins at sites of inflammation, but excessive or prolonged proteolytic activity may cause harmful effects in the body.

Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against constituents of neutrophil cytoplasm. Two main types of ANCA are present in patients with ANCA-associated systemic vasculitis: cANCA (cytoplasmic pattern in indirect immunofluorescence test, IIF), which target PR3, and pANCA (perinuclear), which are directed against MPO. 

cANCA/PR3-ANCA exhibit high specificity as well as sensitivity for Wegener's Granulomatosis, a necrotizing vascultis syndrome, and are much less frequently found in Churg-Strauss Syndrome and Microscopic Polyangiitis. In active Wegener the prevalence of this antibody is almost 90%, decreasing to 30-40% during remission. There is consensus in the literature that diagnostic specificity is optimally improved by combining IIF on neutrophils together with standardized PR3 ELISA. Presently PR3-ANCA is detected by both traditional direct and capture ELISAs; very recently a so-called anchor ELISA (using a bridging molecule to prevent direct adhesion on the plastic surface and therefore preserving all epitopes for binding with ANCA) as well as multiplex systems (e.g. measuring PR3, MPO and GBM autoantibodies in one tube) have also been described.

The close relationship between ANCA and ANCA associated vasculitis, in particular with disease activity, has suggested that ANCA may be pathogenic. Interestingly the parenchymal pneumocytes and macrophages, and not the neutrophils, express PR3 most strongly and may, for instance, contribute to lung damage in patients with WG via direct interaction with ANCA. In this view vascular damage is caused by ANCA-activated leukocytes; whether endothelial damage can arise by direct pathological action of ANCA on endothel cell surface has been speculated for years, but is not rigorously proven.

Human native proteinase 3 (PR3) by DIARECT is purified from polymorphonuclear leukocytes of peripheral human blood.