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Cartilage oligomeric matrix protein specific antibodies are pathogenic

In English

Författare

  • Hui Geng
  • Kutty Selva Nandakumar
  • Anna Pramhed
  • Anders Aspberg
  • Ragnar Mattsson
  • Rikard Holmdahl

Summary, in English

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.

Publiceringsår

2012

Språk

Engelska

Publikation/Tidskrift/Serie

Arthritis Research and Therapy

Volym

14

Issue

4

Dokumenttyp

Artikel i tidskrift

Förlag

BioMed Central (BMC)

Ämne

  • Rheumatology and Autoimmunity

Status

Published

Forskningsgrupp

  • Immunology

ISBN/ISSN/Övrigt

  • ISSN: 1478-6362