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Generation of neoantigenic epitopes after posttranslational modification of type II collagen by factors present within the inflamed joint

  1. Ahuva Nissim1,*,
  2. Paul G. Winyard2,
  3. Valerie Corrigall3,
  4. Rewas Fatah1,
  5. David Perrett1,
  6. Gabriel Panayi3,†,
  7. Yuti Chernajovsky1

Article first published online: 2 DEC 2005

DOI: 10.1002/art.21479

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 52, Issue 12, pages 3829–3838, December 2005

Additional Information

How to Cite

Nissim, A., Winyard, P. G., Corrigall, V., Fatah, R., Perrett, D., Panayi, G. and Chernajovsky, Y. (2005), Generation of neoantigenic epitopes after posttranslational modification of type II collagen by factors present within the inflamed joint. Arthritis & Rheumatism, 52: 3829–3838. doi: 10.1002/art.21479

Author Information

  1. 1

    University of London, London, UK

  2. 2

    Universities of Exeter and Plymouth, St. Luke's Campus, Exeter, UK

  3. 3

    King's College, Guy's Hospital, London, UK

  1. †

    Dr. Panayi has received consulting fees (less than $10,000 per year) from MSD, Abbott, Roche, and Novartis.

*Bone and Joint Research Unit, William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, Charterhouse Square, London EC1M 6BQ, UK

Publication History

  1. Issue published online: 2 DEC 2005
  2. Article first published online: 2 DEC 2005
  3. Manuscript Accepted: 7 SEP 2005
  4. Manuscript Received: 2 MAR 2005

Funded by

  • Arthritis Research Campaign (UK)
  • Research Advisory Board of Barts
  • The London School of Medicine and Dentistry

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Abstract

Objective

Collagen-induced arthritis is a commonly accepted model of rheumatoid arthritis (RA). However, it has been difficult to substantiate the involvement of autoimmunity to type II collagen (CII) in the pathogenesis of RA. The aim of this investigation was to determine if CII, modified by reactive oxidant species present within the inflamed joint, could generate neoantigenic epitopes.

Methods

Oxidants that play a role in acute and chronic inflammation and are present in the rheumatoid joint (hydroxyl radical, hypochlorous acid, and peroxynitrite) were used for modification of native CII. In addition, CII was glycated with ribose, since nonenzymatic oxidative reactions by glycation are evident in RA. Modifications were analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and 3-dimensional fluorescence followed by enzyme-linked immunosorbent assay (ELISA) and Western blotting, using, as probes, sera from patients with RA and from patients with other inflammatory and noninflammatory joint diseases.

Results

Only 1 RA serum sample showed strong binding to native CII. In contrast, binding to modified CII was increased in 14 of 31 RA sera, of which 7 were strong binders and 7 were moderate binders. Among the non-RA serum samples, only 1 yielded a strong reaction to modified CII and 5 of 41 were moderate binders. Samples that showed the strongest binding to modified CII in ELISA also showed strong binding to various fragmented or aggregated forms of CII in Western blots, as well as strong binding to fragmented CII present in RA synovial fluid.

Conclusion

When modified by conditions found within the inflamed joint, CII acts as an autoantigen in RA.

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