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Cartilage oligomeric matrix protein specific antibodies are pathogenic

Geng, Hui; Nandakumar, Kutty Selva; Pramhed, Anna LU ; Aspberg, Anders LU ; Mattsson, Ragnar LU and Holmdahl, Rikard (2012) In Arthritis Research and Therapy 14(4).
Abstract
Introduction: Cartilage oligomeric matrix protein (COMP) is a major non-collagenous component of cartilage. Earlier, we developed a new mouse model for rheumatoid arthritis using COMP. This study was undertaken to investigate the epitope specificity and immunopathogenicity of COMP-specific monoclonal antibodies (mAbs). Methods: B cell immunodominant regions on the COMP molecule were measured with a novel enzyme-linked immunosorbent assay using mammalian expressed full-length mouse COMP as well as a panel of recombinant mouse COMP fragments. 18 mAbs specific to COMP were generated and the pathogenicity of mAbs was investigated by passive transfer experiments. Results: B cell immunodominant epitopes were localized within 4 antigenic domains... (More)
Introduction: Cartilage oligomeric matrix protein (COMP) is a major non-collagenous component of cartilage. Earlier, we developed a new mouse model for rheumatoid arthritis using COMP. This study was undertaken to investigate the epitope specificity and immunopathogenicity of COMP-specific monoclonal antibodies (mAbs). Methods: B cell immunodominant regions on the COMP molecule were measured with a novel enzyme-linked immunosorbent assay using mammalian expressed full-length mouse COMP as well as a panel of recombinant mouse COMP fragments. 18 mAbs specific to COMP were generated and the pathogenicity of mAbs was investigated by passive transfer experiments. Results: B cell immunodominant epitopes were localized within 4 antigenic domains of the COMP but with preferential response to the epidermal growth factor (EGF)-like domain. Some of our anti-COMP mAbs showed interactions with the native form of COMP, which is present in cartilage and synovium. Passive transfer of COMP-specific mAbs enhanced arthritis when co-administrated with a sub-arthritogenic dose of a mAb specific to collagen type II. Interestingly, we found that a combination of 5 COMP mAbs was capable of inducing arthritis in naive mice. Conclusions: We have identified the specificities of mAbs to COMP and their contribution to the development of arthritis. These findings will further improve our understanding of the autoantibody mediated immunopathologies occurring widely in rheumatoid arthritis (RA), as well as in other autoimmune disorders. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis Research and Therapy
volume
14
issue
4
publisher
BioMed Central
external identifiers
  • wos:000314974600035
  • scopus:84865049473
ISSN
1478-6362
DOI
10.1186/ar4022
language
English
LU publication?
yes
id
3942c659-a07c-4444-91a0-291118758aca (old id 3577400)
date added to LUP
2013-04-02 07:44:41
date last changed
2017-08-27 03:30:34
@article{3942c659-a07c-4444-91a0-291118758aca,
  abstract     = {Introduction: Cartilage oligomeric matrix protein (COMP) is a major non-collagenous component of cartilage. Earlier, we developed a new mouse model for rheumatoid arthritis using COMP. This study was undertaken to investigate the epitope specificity and immunopathogenicity of COMP-specific monoclonal antibodies (mAbs). Methods: B cell immunodominant regions on the COMP molecule were measured with a novel enzyme-linked immunosorbent assay using mammalian expressed full-length mouse COMP as well as a panel of recombinant mouse COMP fragments. 18 mAbs specific to COMP were generated and the pathogenicity of mAbs was investigated by passive transfer experiments. Results: B cell immunodominant epitopes were localized within 4 antigenic domains of the COMP but with preferential response to the epidermal growth factor (EGF)-like domain. Some of our anti-COMP mAbs showed interactions with the native form of COMP, which is present in cartilage and synovium. Passive transfer of COMP-specific mAbs enhanced arthritis when co-administrated with a sub-arthritogenic dose of a mAb specific to collagen type II. Interestingly, we found that a combination of 5 COMP mAbs was capable of inducing arthritis in naive mice. Conclusions: We have identified the specificities of mAbs to COMP and their contribution to the development of arthritis. These findings will further improve our understanding of the autoantibody mediated immunopathologies occurring widely in rheumatoid arthritis (RA), as well as in other autoimmune disorders.},
  articleno    = {R191},
  author       = {Geng, Hui and Nandakumar, Kutty Selva and Pramhed, Anna and Aspberg, Anders and Mattsson, Ragnar and Holmdahl, Rikard},
  issn         = {1478-6362},
  language     = {eng},
  number       = {4},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {Cartilage oligomeric matrix protein specific antibodies are pathogenic},
  url          = {http://dx.doi.org/10.1186/ar4022},
  volume       = {14},
  year         = {2012},
}