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

Uysal, Hüseyin; Bockermann, Robert LU ; Kutty Selva, Nandakumar LU ; Sehnert, Bettina; Bajtner, Estelle LU ; Engström, Ake; Serre, Guy; Burkhardt, Harald; Thunnissen, Marjolein LU and Holmdahl, Rikard LU (2009) In Journal of Experimental Medicine 206(2). p.449-462
Abstract
Antibodies to citrulline-modified 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 modified by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients' synovial fluid 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... (More)
Antibodies to citrulline-modified 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 modified by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients' synovial fluid 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
206
issue
2
pages
449 - 462
publisher
Rockefeller University Press
external identifiers
  • wos:000266008800017
  • pmid:19204106
  • scopus:63049101247
ISSN
1540-9538
DOI
10.1084/jem.20081862
language
English
LU publication?
yes
id
7a03394d-e94c-4555-9894-239351101546 (old id 1302751)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19204106?dopt=Abstract
date added to LUP
2009-03-05 16:44:08
date last changed
2017-07-23 05:00:54
@article{7a03394d-e94c-4555-9894-239351101546,
  abstract     = {Antibodies to citrulline-modified 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 modified by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients' synovial fluid 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.},
  author       = {Uysal, Hüseyin and Bockermann, Robert and Kutty Selva, Nandakumar and Sehnert, Bettina and Bajtner, Estelle and Engström, Ake and Serre, Guy and Burkhardt, Harald and Thunnissen, Marjolein and Holmdahl, Rikard},
  issn         = {1540-9538},
  language     = {eng},
  number       = {2},
  pages        = {449--462},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis.},
  url          = {http://dx.doi.org/10.1084/jem.20081862},
  volume       = {206},
  year         = {2009},
}