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Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis
  1. H de Jong1,2,
  2. S E Berlo1,3,
  3. P Hombrink1,
  4. H G Otten4,
  5. W van Eden2,
  6. F P Lafeber3,
  7. A H M Heurkens5,
  8. J W J Bijlsma3,
  9. T T Glant6,
  10. B J Prakken1
  1. 1
    Department of Paediatric Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2
    Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands
  3. 3
    Department of Infectious Diseases and Immunology, Division of Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  4. 4
    Department of Immunology, University Medical Center, Utrecht, The Netherlands
  5. 5
    Department of Rheumatology, Meander Medical Center, Amersfoort, The Netherlands
  6. 6
    Section of Molecular Medicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois, USA
  1. Correspondence to ProfessorDr B J Prakken, Department of Paediatric Immunology, KC.01.069.0, UMC Utrecht, Location WKZ, Lundlaan 6, 3584 EA Utrecht, The Netherlands; B.Prakken{at}umcutrecht.nl

Abstract

Objectives: To explore potential T-cell epitopes of the core protein of human cartilage proteoglycan aggrecan (PG) in patients with rheumatoid arthritis (RA) or osteoarthritis.

Methods: Peptide-specific T-cell proliferation and cytokine/chemokine production in response to PG-specific peptides were measured in RA and osteoarthritis patients and in healthy controls.

Results: Peptides representing amino acid regions 16–39 and 263–282 of PG were most frequently recognised by T cells in a subset of patients with RA or osteoarthritis. Peripheral blood mononuclear cells from these PG-reactive RA and osteoarthritis patients showed increased production of proinflammatory cytokines/chemokines in response to PG peptide stimulation. As PG p263–282 was found to show high sequence homology with Yersinia Yop protein, the corresponding bacterial (Yersinia) peptide was also tested. Remarkably, RA and osteoarthritis patients responding to the Yersinia peptide also responded to p263–282 of PG suggesting a possibility of molecular mimicry in these patients.

Conclusions: These results indicate that PG-specific peptides, located in the G1 domain of PG, can induce (auto)antigenic T-cell responses in RA and osteoarthritis patients. These peptides might thus be involved in the immune pathogenesis and/or cartilage degradation in RA and osteoarthritis.

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Footnotes

  • ▸ Additional supplemental table 5 is published online only at http://ard.bmj.com/content/vol69/issue1

  • Funding This work was supported by grants from the Dutch Arthritis Association and the National Institutes of Health.

  • Competing interests None.

  • Ethics approval This study was approved by the Institutional Ethical Committee.

  • The first two authors and the last two authors were equally involved in this work.

  • Provenance and Peer review Not commissioned; externally peer reviewed.

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