Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1302751
- author
- 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
- organization
- publishing date
- 2009
- 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
- pmid:19204106
- ISSN
- 1540-9538
- DOI
- 10.1084/jem.20081862
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Biochemistry and Structural Biology (S) (000006142), Medical Inflammation Research (013212019)
- 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
- 2016-04-04 09:41:41
- date last changed
- 2024-11-11 07:07:14
@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 = {{https://lup.lub.lu.se/search/files/5392578/1389740.pdf}}, doi = {{10.1084/jem.20081862}}, volume = {{206}}, year = {{2009}}, }