Anti-neutrophil cytoplasmic antibodies target sequential functional proteinase 3 epitopes in the sera of patients with Wegener's granulomatosis

摘要: Many patients with Wegener’s granulomatosis (WG) have anti-neutrophil cytoplasmic antibodies (c-ANCA). Aside from being a diagnostic marker, these autoantibodies may play roles in disease pathogenesis. Proteinase 3 (PR3) is the primary target of c-ANCA WG patient sera. Of 60 c-ANCA-positive patients, 10 were selected for detailed humoral epitope analysis, contingent upon serum availability, using samples positive levels anti-PR3 by enzyme-linked immunosorbent assay (ELISA). Sequential specificities detected screening maximally overlapping solid-phase octapeptides PR3 showed seven major common antigenic targets bound These include novel and previously identified sequential epitopes c-ANCA. B cell prediction algorithms all or part defined epitopes. Several share sequence structural proximity functional sites, including catalytic triad proposed binding sites other potential proteins [PR3 complementary peptide soluble endothelial protein C receptor (sEPCR)]. Epitope 4 (VVLGAHNVRTQ) had highest prevalence (90%) 2 (AQPHSRPYMAS) has average reactivity regions. includes interaction site between sEPCR which serve as an important to down-regulate inflammation. Epitopes 3, 5 7 are direct amino acids that form protein. both unique known peptides. This information prove useful understanding anti-PR3-mediated pathogenesis systemic vasculitides.