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          Institute: MPI für Neurobiologie     Collection: Neuroimmunology     Display Documents



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ID: 522624.0, MPI für Neurobiologie / Neuroimmunology
Discrimination and variable impact of ANCA binding to different surface epitopes on proteinase 3, the Wegener's autoantigen
Authors:Silva, F.; Hummel, A. M.; Jenne, D. E.; Specks, U.
Language:English
Date of Publication (YYYY-MM-DD):2010-12
Title of Journal:Journal of Autoimmunity
Journal Abbrev.:J. Autoimmun.
Volume:35
Issue / Number:4
Start Page:299
End Page:308
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Proteinase 3 (PR3)-specific antineutrophil cytoplasmic antibodies (ANCA) are highly specific for the autoimmune small vessel vasculitis Wegener s granulomatosis (WG) PR3-ANCA have proven diagnostic value but their pathogenic potential and utility as a biomarker for disease activity remain unclear PR3-ANCA recognize conformational epitopes and epitope-specific PR3-ANCA subsets with variable impact on biological functions of PR3 have been postulated The aims of this study were to identify specific PR3 surface epitopes recognized by monoclonal antibodies (moAbs) and to determine whether the findings can be used to measure the functional impact of epitope-specific PR3-ANCA and their potential relationship to disease activity We used a novel flow cytometry assay based on TALON-beads coated with recombinant human (H) and murine (M) PR3 and 10 custom-designed chimeric human/mouse rPR3-variants (Hm1-5/Mh1-5) identifying 5 separate non-conserved PR3 surface epitopes Anti-PR3 moAbs recognize 4 major surface epitopes and we identified the specific surface location of 3 of these with the chimeric rPR3-variants The ability of PR3-ANCA to inhibit the enzymatic activity of PR3 was measured indirectly using a capture-ELISA system based on the different epitopes recognized by capturing moAbs Epitope-specific PR3-ANCA capture-ELISA results obtained from patient plasma (n = 27) correlated with the inhibition of enzymatic activity of PR3 by paired IgG preparations (r = 07 P < 0 01) The capture-ELISA results also seem to reflect disease activity In conclusion insights about epitopes recognized by anti-PR3 moAbs can be applied to separate PR3-ANCA subsets with predictable functional qualities The ability of PR3-ANCA to inhibit the enzymatic activity of PR3 a property linked to disease activity can now be gauged using a simple epitope-based capture-ELISA system (c) 2010 Elsevier Ltd All rights reserved
Free Keywords:ANCA; Proteinase 3; Wegener s granulomatosis; Vasculitis
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Affiliations:MPI für Neurobiologie/Neuroimmunology (Wekerle)
External Affiliations:[Silva, Francisco; Hummel, Amber M.; Specks, Ulrich] Mayo Clin & Mayo Fdn, Div Pulm & Crit Care Med, Thorac Dis Res Unit, Rochester, MN 55905 USA.
Identifiers:ISI:000284567700002 [ID No:1]
ISSN:0896-8411 [ID No:2]
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