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. 1989 Nov;78(2):177–183.

Pattern of humoral reactivity to type II collagen in rheumatoid arthritis.

M C Boissier 1, G Chiocchia 1, B Texier 1, C Fournier 1
PMCID: PMC1534662  PMID: 12412745

Abstract

Humoral immunity directed against type II collagen (CII) is a common although not specific feature of rheumatoid arthritis (RA). We have shown that 10 to 15% of the sera either from RA patients (n = 88) or from healthy controls (n = 149) reacted with native human CII. Conversely, autoantibodies to the alpha-1 (II) chains were significantly more frequent in the RA group (26.1% versus 6.0%, P<0.001), suggestingthatdenaturedCII may bean autoantigenin RA. Thus, human CII was cleaved with cyanogen bromide (CB), and immunoblotting techniques were performed on 19 RA and 21 normal sera. Among the four major CB peptides, CB10 and CB11 were recognized by most of the sera tested without distinction between normal or RA sera. Inhibition experiments using an ELISA have shown that: (i) antibodies to the native CII molecule did not cross-react with those recognizing the CB peptides, and vice-versa; (ii) the binding of the sera to native CII was partially inhibited by pre-incubation with alpha-1 (II) chains, and vice-versa; (iii) pre-incubation of the sera with CB peptides partially blocked the binding to alpha-1 (II) chains, whereas pre-incubation of the sera with alpha-1 (II) chains totally inhibited the reactivity against CB peptides; and (iv) a substantial proportion of the epitopes recognized by anti-CII autoantibodies was neither species specific nor type specific. Taken together, these findings reveal the existence of several populations of anti-CII autoantibodies: some antibodies react exclusively with conformational determinants of the CII molecule, and others are directed towards linear structures of alpha-1 (II) chains.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Charrière G., Hartmann D. J., Vignon E., Ronzière M. C., Herbage D., Ville G. Antibodies to types I, II, IX, and XI collagen in the serum of patients with rheumatic diseases. Arthritis Rheum. 1988 Mar;31(3):325–332. doi: 10.1002/art.1780310303. [DOI] [PubMed] [Google Scholar]
  2. Choi E. K., Gatenby P. A., McGill N. W., Bateman J. F., Cole W. G., York J. R. Autoantibodies to type II collagen: occurrence in rheumatoid arthritis, other arthritides, autoimmune connective tissue diseases, and chronic inflammatory syndromes. Ann Rheum Dis. 1988 Apr;47(4):313–322. doi: 10.1136/ard.47.4.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clague R. B., Firth S. A., Holt P. J., Skingle J., Greenbury C. L., Webley M. Serum antibodies to type II collagen in rheumatoid arthritis: comparison of 6 immunological methods and clinical features. Ann Rheum Dis. 1983 Oct;42(5):537–544. doi: 10.1136/ard.42.5.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Courtenay J. S., Dallman M. J., Dayan A. D., Martin A., Mosedale B. Immunisation against heterologous type II collagen induces arthritis in mice. Nature. 1980 Feb 14;283(5748):666–668. doi: 10.1038/283666a0. [DOI] [PubMed] [Google Scholar]
  5. Englert M. E., Ferguson K. M., Suarez C. R., Oronsky A. L., Kerwar S. S. Passive transfer of collagen arthritis: heterogeneity of anti-collagen IgG. Cell Immunol. 1986 Sep;101(2):373–379. doi: 10.1016/0008-8749(86)90150-4. [DOI] [PubMed] [Google Scholar]
  6. Englert M. E., Ferguson K. M., Suarez C. R., Sapp T. M., Oronsky A. L., Kerwar S. S. Type II collagen arthritis: identification of arthritogenic epitopes using fractionated anticollagen IgG. Cell Immunol. 1987 Apr 1;105(2):447–453. doi: 10.1016/0008-8749(87)90092-x. [DOI] [PubMed] [Google Scholar]
  7. Holmdahl R., Jansson L., Gullberg D., Rubin K., Forsberg P. O., Klareskog L. Incidence of arthritis and autoreactivity of anti-collagen antibodies after immunization of DBA/1 mice with heterologous and autologous collagen II. Clin Exp Immunol. 1985 Dec;62(3):639–646. [PMC free article] [PubMed] [Google Scholar]
  8. Holmdahl R., Rubin K., Klareskog L., Larsson E., Wigzell H. Characterization of the antibody response in mice with type II collagen-induced arthritis, using monoclonal anti-type II collagen antibodies. Arthritis Rheum. 1986 Mar;29(3):400–410. doi: 10.1002/art.1780290314. [DOI] [PubMed] [Google Scholar]
  9. Iribe H., Kabashima H., Ishii Y., Koga T. Epitope specificity of antibody response against human type II collagen in the mouse susceptible to collagen-induced arthritis and patients with rheumatoid arthritis. Clin Exp Immunol. 1988 Sep;73(3):443–448. [PMC free article] [PubMed] [Google Scholar]
  10. Iribe H., Kabashima H., Kakimoto K., Koga T. Induction of an anti-human type II collagen response by monoclonal anti-idiotypic antibody. J Immunol. 1988 Jun 15;140(12):4151–4156. [PubMed] [Google Scholar]
  11. Kammer G. M., Trentham D. E. HLA-DR4 is not a requisite for autoimmunity to collagen in rheumatoid arthritis. Arthritis Rheum. 1984 May;27(5):489–494. doi: 10.1002/art.1780270502. [DOI] [PubMed] [Google Scholar]
  12. Klareskog L., Johnell O., Hulth A., Holmdahl R., Rubin K. Reactivity of monoclonal anti-type II collagen antibodies with cartilage and synovial tissue in rheumatoid arthritis and osteoarthritis. Arthritis Rheum. 1986 Jun;29(6):730–738. doi: 10.1002/art.1780290605. [DOI] [PubMed] [Google Scholar]
  13. Klimiuk P. S., Clague R. B., Grennan D. M., Dyer P. A., Smeaton I., Harris R. Autoimmunity to native type II collagen--a distinct genetic subset of rheumatoid arthritis. J Rheumatol. 1985 Oct;12(5):865–870. [PubMed] [Google Scholar]
  14. Miller E. J. Isolation and characterization of the cyanogen bromide peptides from the l(II) chain of chick cartilage collagen. Biochemistry. 1971 Aug 3;10(16):3030–3035. doi: 10.1021/bi00792a007. [DOI] [PubMed] [Google Scholar]
  15. Morgan K., Clague R. B., Collins I., Ayad S., Phinn S. D., Holt P. J. Incidence of antibodies to native and denatured cartilage collagens (types II, IX, and XI) and to type I collagen in rheumatoid arthritis. Ann Rheum Dis. 1987 Dec;46(12):902–907. doi: 10.1136/ard.46.12.902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. ROPES M. W., BENNETT G. A., COBB S., JACOX R., JESSAR R. A. 1958 Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis. 1958 Dec;9(4):175–176. [PubMed] [Google Scholar]
  17. Rowley M. J., Gershwin M. E., Mackay I. R. Collagen antibodies in juvenile arthritis and adult rheumatoid arthritis: differences in levels and type-specificity. J Rheumatol. 1988 Feb;15(2):289–294. [PubMed] [Google Scholar]
  18. Rowley M. J., Williamson D. J., Mackay I. R. Evidence for local synthesis of antibodies to denatured collagen in the synovium in rheumatoid arthritis. Arthritis Rheum. 1987 Dec;30(12):1420–1425. doi: 10.1002/art.1780301215. [DOI] [PubMed] [Google Scholar]
  19. Rowley M., Tait B., Mackay I. R., Cunningham T., Phillips B. Collagen antibodies in rheumatoid arthritis. Significance of antibodies to denatured collagen and their association with HLA-DR4. Arthritis Rheum. 1986 Feb;29(2):174–184. doi: 10.1002/art.1780290204. [DOI] [PubMed] [Google Scholar]
  20. Solinger A. M., Bhatnagar R., Stobo J. D. Cellular, molecular, and genetic characteristics of T cell reactivity to collagen in man. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3877–3881. doi: 10.1073/pnas.78.6.3877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ström H., Al-Balaghi S., Möller E. No demonstrable association between HLA DR4 and in vitro collagen reactivity as determined by the production of leukocyte inhibition factor. Tissue Antigens. 1984 Sep;24(3):174–183. doi: 10.1111/j.1399-0039.1984.tb02123.x. [DOI] [PubMed] [Google Scholar]
  22. Stuart J. M., Huffstutter E. H., Townes A. S., Kang A. H. Incidence and specificity of antibodies to types I, II, III, IV, and V collagen in rheumatoid arthritis and other rheumatic diseases as measured by 125I-radioimmunoassay. Arthritis Rheum. 1983 Jul;26(7):832–840. doi: 10.1002/art.1780260703. [DOI] [PubMed] [Google Scholar]
  23. Stuart J. M., Townes A. S., Kang A. H. Nature and specificity of the immune response to collagen in type II collagen-induced arthritis in mice. J Clin Invest. 1982 Mar;69(3):673–683. doi: 10.1172/JCI110495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Terato K., Hasty K. A., Cremer M. A., Stuart J. M., Townes A. S., Kang A. H. Collagen-induced arthritis in mice. Localization of an arthritogenic determinant to a fragment of the type II collagen molecule. J Exp Med. 1985 Aug 1;162(2):637–646. doi: 10.1084/jem.162.2.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Trentham D. E., Kammer G. M., McCune W. J., David J. R. Autoimmunity to collagen: a shared feature of psoriatic and rheumatoid arthritis. Arthritis Rheum. 1981 Nov;24(11):1363–1369. doi: 10.1002/art.1780241105. [DOI] [PubMed] [Google Scholar]
  26. Trentham D. E., Townes A. S., Kang A. H. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 1977 Sep 1;146(3):857–868. doi: 10.1084/jem.146.3.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Verbruggen L. A., Geerts A., Wisse E., Lapiere C. Serum and synovial fluid antibodies to collagen in rheumatic diseases: a review. Clin Rheumatol. 1986 Dec;5(4):440–444. [PubMed] [Google Scholar]
  28. Wooley P. H., Luthra H. S., Griffiths M. M., Stuart J. M., Huse A., David C. S. Type II collagen-induced arthritis in mice. IV. Variations in immunogenetic regulation provide evidence for multiple arthritogenic epitopes on the collagen molecule. J Immunol. 1985 Oct;135(4):2443–2451. [PubMed] [Google Scholar]
  29. Wooley P. H., Luthra H. S., O'Duffy J. D., Bunch T. W., Moore S. B., Stuart J. M. Anti-type II collagen antibodies in rheumatoid arthritis. The influence of HLA phenotype. Tissue Antigens. 1984 May;23(5):263–269. doi: 10.1111/j.1399-0039.1984.tb00043.x. [DOI] [PubMed] [Google Scholar]

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