Abstract
We studied arthritis-related autoantibodies in 136 patients with knee osteoarthritis (OA) and 67 age- and sex-matched healthy individuals in the Shanghai District of China. Serum antibody titers for recombinant fusion proteins of cartilage intermediate layer protein (CILP) and YKL-39 were analyzed using enzyme-linked immunosorbent assay (ELISA) and Western blot. Serum antibody titers against recombinant osteopontin (OPN) and cyclic citrullinated peptide (CCP) antibodies were measured also using ELISA. Anti-CILP antibodies were detected in 25/136 OA patients but only 1/67 controls. Anti-YKL-39, anti-OPN, and anti-CCP antibodies were detected in 9/136, 11/136, and 7/136 of the OA patients, respectively, and 0/67 controls. There was rarely overlap of these antibodies in a single patient, suggesting distinct antigen specificity in each case. The antibodies were detected in patients with OA of grades II and III but not grade IV. The prevalence of autoantibodies to various arthritis-related proteins in early-stage knee OA supports the involvement of a specific immune response in initial cartilage degeneration in OA.
Similar content being viewed by others
References
Sakkas LI, Scanzello C, Johanson N, Burkholder J, Mitra A, Salgame P, Katsetos CD, Platsoucas CD (1998) T cells and T-cell cytokine transcripts in the synovial membrane in patients with osteoarthritis. Clin Diagn Lab Immunol 5:430–437
Jasin HE (1985) Autoantibody specificities of immune complexes sequestered in articular cartilage of patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum 28:241–248
Revell PA, Mayston V, Lalor P, Mapp P (1988) The synovial membrane in osteoarthritis: a histological study including the characterisation of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal antibodies. Ann Rheum Dis 47:300–307
Pattrick M, Manhire A, Ward AM, Doherty M (1989) HLA-A, B antigens and alpha 1-antitrypsin phenotypes in nodal generalised osteoarthritis and erosive osteoarthritis. Ann Rheum Dis 48:470–475
Doherty M, Pattrick M, Powell R (1990) Nodal generalised osteoarthritis is an autoimmune disease. Ann Rheum Dis 49:1017–1020
Shuckett R, Russell ML, Gladman DD (1986) Atypical erosive osteoarthritis and Sjögren’s syndrome. Ann Rheum Dis 45:281–288
Stamenkovic I, Stegagno M, Wright KA, Krane SM, Amento EP, Colvin RB, Duquesnoy RJ, Kurnick JT (1988) Clonal dominance among T-lymphocyte infiltrates in arthritis. Proc Natl Acad Sci U S A 85:1179–1183
Nakamura H, Yoshino S, Kato T, Tsuruha J, Nishioka K (1999) T-cell mediated inflammatory pathway in osteoarthritis. Osteoarthritis Cartilage 7:401–402
Lorenzo P, Bayliss MT, Heinegard D (1998) A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age. J Biol Chem 273:23463–23468
Lorenzo P, Neame P, Sommarin Y, Heinegard D (1998) Cloning and deduced amino acid sequence of a novel cartilage protein (CILP) identifies a proform including a nucleotide pyrophosphohydrolase. J Biol Chem 273:23469–23475
Hu B, Trinh K, Figueira WF, Price PA (1996) Isolation and sequence of a novel human chondrocyte protein related to mammalian members of the chitinase protein family. J Biol Chem 271:19415–19420
Tsuruha J, Masuko-Hongo K, Kato T, Sakata M, Nakamura H, Nishioka K (2001) Implication of cartilage intermediate layer protein in cartilage destruction in subsets of patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum 44:838–845
Tsuruha J, Masuko-Hongo K, Kato T, Sakata M, Nakamura H, Sekine T, Takigawa M, Nishioka K (2002) Autoimmunity against YKL-39, a human cartilage-derived protein, in patients with osteoarthritis. J Rheumatol 29:1459–1466
Sakata M, Tsuruha JI, Masuko-Hongo K, Nakamura H, Matsui T, Sudo A, Nishioka K, Kato T (2001) Autoantibodies to osteopontin in patients with osteoarthritis and rheumatoid arthritis. J Rheumatol 28:1492–1495
Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ (1998) Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 101:273–281
Mediwake R, Isenberg DA, Schellekens GA, van Venrooij WJ (2001) Use of anti-citrullinated peptide and anti-RA33 antibodies in distinguishing erosive arthritis in patients with systemic lupus erythematosus and rheumatoid arthritis. Ann Rheum Dis 60:67–68
Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M et al (1986) Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 29:1039–1049
Kroot EJ, de Jong BA, van Leeuwen MA, Swinkels H, van den Hoogen FH, van’t Hof M, van de Putte LB, van Rijswijk MH, van Venrooij WJ, van Riel PL (2000) The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum 43:1831–1835
Acknowledgements
The authors thank Ms. Mie Kanke, Ms. Toshiko Mogi, and Ms. Hiroe Ogasawara for their excellent technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Du, H., Masuko-Hongo, K., Nakamura, H. et al. The prevalence of autoantibodies against cartilage intermediate layer protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients with early-stage knee osteoarthritis: evidence of a variety of autoimmune processes. Rheumatol Int 26, 35–41 (2005). https://doi.org/10.1007/s00296-004-0497-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-004-0497-2