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Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T cell responses in rheumatoid arthritis and osteoarthritis
  1. Huib de Jong (h.dejong-4{at}umcutrecht.nl)
  1. Department of Paediatric Immunology, University Medical Center Utrecht, Netherlands
    1. Suzanne E Berlo (suzanne_berlo{at}hotmail.com)
    1. Department of Infectious Diseases and Immunology, Division of Immunology, Faculty of Veterinary Med, Netherlands
      1. Pleun Hombrink
      1. Department of Paediatric Immunology, University Medical Center Utrecht, Netherlands
        1. Henny G Otten (hotten{at}umcutrecht.nl)
        1. Department of Paediatric Immunology, University Medical Center Utrecht, Netherlands
          1. Willem van Eden (w.vaneden{at}uu.nl)
          1. Department of Infectious Diseases and Immunology, Division of Immunology, Faculty of Veterinary Med, Netherlands
            1. Floris P Lafeber (f.lafeber{at}umcutrecht.nl)
            1. Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Netherlands
              1. Anton H M Heurkens (ahm.heurkens{at}meandermc.nl)
              1. Department of Rheumatology, Meander Medical Center, Amersfoort, Netherlands
                1. Johannes W J Bijlsma (j.w.j.bijlsma{at}umcutrecht.nl)
                1. Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Netherlands
                  1. Tibor T Glant (tibor_glant{at}rush.edu)
                  1. Section of Molecular Medicine, Department of Orthopedic Surgery, Rush University Medical Center, Chi, United States
                    1. Berent Prakken (b.prakken{at}umcutrecht.nl)
                    1. Department of Paediatric Immunology, University Medical Center Utrecht, Netherlands

                      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 (OA).

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

                      Results: Peptides representing amino acid regions 16-39 and 263-282 of PG were most frequently recognized by T cells in a subset of patients with RA or OA. Peripheral blood mononuclear cells (PBMC) from these PG-reactive RA and OA 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 OA 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 OA patients. Thus these peptides might be involved in the immune pathogenesis and/or cartilage degradation in RA and OA.

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