Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis

Antibodies to citrulline-modifi ed proteins have a high diagnostic value in rheumatoid arthritis (RA). However, their biological role in disease development is still unclear. To obtain insight into this question, a panel
Antibodies to citrulline-modifi ed proteins have a high diagnostic value in rheumatoid arthritis (RA). However, their biological role in disease development is still unclear. To obtain insight into this question, a panel of mouse monoclonal antibodies was generated against a major triple helical collagen type II (CII) epitope (position 359 – 369; ARGLTGRPGDA) with or without arginines modifi ed by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients ’ synovial fl uid demonstrates that cartilage-derived CII is indeed citrullinated in vivo. The structure determination of a Fab fragment of one of these antibodies in complex with a citrullinated peptide showed a surprising beta -turn conformation of the peptide and provided information on citrulline recognition. Based on these findings, we propose that autoimmunity to CII, leading to the production of antibodies specific for both native and citrullinated CII, is an important pathogenic factor in the development of RA.
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Author:Hüseyin Uysal, Robert Bockermann, Kutty S. Nandakumar, Bettina Sehnert, Estelle Bajtner, Åke Engström, Guy Serre, Harald Burkhardt, Marjolein M. G. M. Thunnissen, Rikard Holmdahl
URN:urn:nbn:de:hebis:30-69816
DOI:http://dx.doi.org/10.1084/jem.20081862
Parent Title (German):The Journal of Experimental Medicine
Document Type:Article
Language:English
Date of Publication (online):2009/09/07
Date of first Publication:2009/02/09
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2009/09/07
Volume:2009
Note:
© 2009 Uysal et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Source:The Journal of Experimental Medicine, Published online February 9, 2009 ; DOI: 10.1084/jem.20081862 ; http://www.jem.org/cgi/doi/10.1084/jem.20081862
HeBIS PPN:218274351
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License Logo Veröffentlichungsvertrag für Publikationen

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