Epitopes described in "Anti-neutrophil cytoplasmic antibodies target sequential functional proteinase 3 epitopes in the sera of patients with Wegener’s granulomatosis."

Article Authors:B F Bruner; E S Vista; D M Wynn; J B Harley; J A James
Article Title:Anti-neutrophil cytoplasmic antibodies target sequential functional proteinase 3 epitopes in the sera of patients with Wegener’s granulomatosis.
Reference Detail
Reference ID:1021372
Abstract: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 in WG patient sera. Of 60 c-ANCA-positive patients, 10 patients were selected for detailed humoral epitope analysis, contingent upon serum availability, using samples with positive levels of anti-PR3 by enzyme-linked immunosorbent assay (ELISA). Sequential epitope specificities of anti-PR3 antibodies detected by screening the maximally overlapping solid-phase octapeptides of PR3 showed seven major common antigenic targets bound by WG patient sera. These include novel and previously identified sequential PR3 epitopes bound by c-ANCA. B cell epitope prediction algorithms identified all or part of the seven defined epitopes. Several epitopes share sequence and structural proximity with functional sites, including the catalytic triad and proposed binding sites of other potential proteins [PR3 complementary peptide and soluble endothelial protein C receptor (sEPCR)]. Epitope 4 (VVLGAHNVRTQ) had the highest binding prevalence (90%) and epitope 2 (AQPHSRPYMAS) has the highest average reactivity of the antigenic regions. Epitope 4 includes the interaction site between sEPCR and PR3 which may serve as an important interaction to down-regulate inflammation. Epitopes 3, 5 and 7 are in direct proximity to amino acids that form the catalytic triad of the protein. c-ANCA targets both unique and previously known sequential PR3 peptides. This information may prove useful in understanding anti-PR3-mediated disease pathogenesis in systemic vasculitides.
Affiliations:Oklahoma Medical Research Foundation, Oklahoma City, 73104, USA.
Reference Type:Literature
PubMed ID:21077276
Journal:Clin Exp Immunol
Journal Volume:162
Article Pages:262-70
Journal ISSN:0009-9104
Article Chemical List:Antibodies, Antineutrophil Cytoplasmic;Epitopes, B-Lymphocyte;Peptide Fragments;Myeloblastin
Article MeSH List:Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Amino Acid Sequence; Antibodies, Antineutrophil Cytoplasmic(blood; immunology); Epitopes, B-Lymphocyte(chemistry; immunology); Female; Granulomatosis with Polyangiitis(immunology); Humans; Isoelectric Point; Male; Middle Aged; Models, Molecular; Myeloblastin(chemistry; immunology); Peptide Fragments(chemistry; immunology); Surface Properties; Young Adult
Curation Last Updated:2015-06-05 02:33:31