Comparative Epitope Mapping of Antibodies to Collagen in Women with Silicone Breast Implants, Systemic Lupus Erythematosus and Rheumatoid Arthritis

  • M. J. Rowley
  • A. D. Cook
  • I. R. Mackay
  • S. S. Teuber
  • M. E. Gershwin
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 210)


Previous work has shown that women with silicone gel breast implants have an increased frequency of autoantibodies to collagen types I and II. 70 women without a specific autoimmune disease, using criteria of the American College of Rheumatology, but who had silicone breast implants were studied for the presence of serum antibodies to native and denatured human types I and II collagen by ELISA. 82 women with systemic lupus erythematosus (SLE), 94 women with rheumatoid arthritis (RA), and 133 healthy controls were also studied. There was a high frequency of autoantibodies to collagen in each of the groups when compared to the healthy controls. The specificities of these antibodies were found to differ markedly when examined by immunoblotting using peptides derived by cyanogen bromide digestion of the collagens. Sera from women with silicone implants reacted with multiple peptides of type I collagen in an individual-specific manner, but sera from women with SLE or RA reacted weakly with a restricted range of peptides. Against type II collagen, sera from women with RA reacted strongly with multiple peptides, while sera from women with silicone implants or SLE reacted only weakly or not at all. The patterns of reactivity against collagens by sera from women with silicone implants suggest that silicone can act as an adjuvant to enhance the immunogenicity of type I collagen.


Rheumatoid Arthritis Systemic Lupus Erythematosus Breast Implant Capsular Contracture Cyanogen Bromide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Mikuz G, Hoinkes G, Propst A, Wilflingseder P (1984) Tissue reactions with silicone rubber implants (morphological, microchemical, and clinical investigations in humans and laboratory animals). In: Macromolecular Biomaterials. G.M. Hartings and P. Ducheyne, Eds. CRC Press, Inc. Boca Raton, Florida 239–249Google Scholar
  2. 2.
    Travis WD, Balogh K, Abraham JL (1985) Silicone granulomas: report of three cases and a review of the literature. Human Pathol 16:19CrossRefGoogle Scholar
  3. 3.
    Van Nunen SA, Gatenby PA, Basten A (1992) Post-mammoplasty connective tissue disease. Arthritis Rheum 25:694–697Google Scholar
  4. 4.
    Spiera H, Dubin Kerr L (1992) Scleroderma following silicone implantation: a cumulative experience of 11 cases. J Rheumatol 20:958–961Google Scholar
  5. 5.
    Bridges AJ, Conley C, Wang G, Burns E, Vasey FB (1993) A clinical and immunologic evaluation of women with silicone breast implants and symptoms of rheumatic disease. Ann Intern Med 118:929–936PubMedGoogle Scholar
  6. 6.
    Press RI, Peebles CL, Kumagai Y, Ochs RL, Tan EM (1992) Antinuclear autoantibodies in women with silicone breast implants. Lancet 340:1304–1307PubMedCrossRefGoogle Scholar
  7. 7.
    Nairn JO, Lanzafame RJ (1993) The adjuvant effect of silicone gel on antibody formation in rats. Immunol Invest 22:151–161CrossRefGoogle Scholar
  8. 8.
    Seleznick MJ, Martinez-Osuna P, Espinoza LR, Vasey FB (1991) Is silicone associated with connective tissue disease? J Florida MA 78:85–87Google Scholar
  9. 9.
    Kossovsky N, Zeidler M, Chum G, Papasian N, Nguyen A, Rajguru A, Stassi J, Gelman A, Sponsier E (1993) Surface dependent antigens identified by high binding avidity of serum antibodies in a subpopulation of patients with breast prostheses. J Applied Biomaterials 4:281–288CrossRefGoogle Scholar
  10. 10.
    Stuart JM, Huffstutter EH, Townes AS, Kang AH (1993) Incidence and specificity of antibodies of types I, II, III, IV, and V collagen in rheumatoid arthritis and other rheumatic diseases as measured by 1251-radioimmunoassay. Arthritis Rheum 26:832–840CrossRefGoogle Scholar
  11. 11.
    Choi EKK, Gatenby PA, McGill NW, Bateman JF, Cole WG, York JR (1988) Autoantibodies to type II collagen: occurrence in rheumatoid arthritis, other arthritides, autoimmune connective tissue diseases, and chronic inflammatory syndromes. Ann Rheum Dis 47:313–319PubMedCrossRefGoogle Scholar
  12. 12.
    Charriere G, Hartmann DJ, Vignon E, Ronziere MC, Herbage D, Ville G (1988) Antibodies to types I, II, IX and XI collagen in the serum of patients with rheumatic diseases. Arthritis Rheum 31:325PubMedCrossRefGoogle Scholar
  13. 13.
    Rowley MJ, Gershwin ME, Mackay IR (1988) Collagen antibodies in juvenile arthritis and adult rheumatoid arthritis: differences in levels and type-specificity. J Rheumatol 15:289–293PubMedGoogle Scholar
  14. 14.
    Moreland LW, Gay RE, Gay S (1991) Collagen autoantibodies in patients with vasculitis and systemic lupus erythematosus. Clin Immunol Immunopathol 60:412–418PubMedCrossRefGoogle Scholar
  15. 15.
    Rowley MJ, Mackay IR, Brand CA, Batemen JF, Chan D (1992) Epitope specificity of antibodies to type II collagen in rheumatoid arthritis and systemic lupus erythematosus. Rheumatol Int 12:65–68PubMedCrossRefGoogle Scholar
  16. 16.
    Teuber SS, Rowley MJ, Yoshida SH, Ansari AA, Gershwin ME (1993) Anti-collagen autoantibodies are found in women with silicone breast implants. J Autoimmunity 6:367CrossRefGoogle Scholar
  17. 17.
    Rowley MJ, Cook AD, Teuber SS, Gershwin ME (1994) Antibodies to collagen: comparative epitope mapping in women with silicone breast implants, systemic lupus erythematosus and rheumatoid arthritis. J Autoimmunity 7:775–789CrossRefGoogle Scholar
  18. 18.
    Scott PG, Veis A (1976) The cyanogen bromide peptides of bovine soluble and insoluble collagens. Connect Tissue Res 4:107PubMedCrossRefGoogle Scholar
  19. 19.
    Bornstein P, Sage H (1980) Structurally distinct collagen types. Ann Rev Biochem 49:957PubMedCrossRefGoogle Scholar
  20. 20.
    Miller EJ, Rhodes RK (1982) Preparation and characterization of the different types of collagen. Methods Enzymol 82:51–59Google Scholar
  21. 21.
    Woodruff T, Cook A, Rowley M, Mackay I (1994) Antibodies to type II collagen in human serum: storage effects and role of IgM anti-idiotype inregulation. J Rheumatol. 21:197PubMedGoogle Scholar
  22. 22.
    Clague RB, Shaw MJ, Holt PJL (1980) Incidence of serum antibodies to native type I and type II collagens of patients with inflammatory arthritis. Ann Rheum Dis 39:201–206PubMedCrossRefGoogle Scholar
  23. 23.
    Gioud M, Meghlaoui A, Costa O, Monier JC (1982) Antibodies to native type I and type II collagens detected by an enzyme linked immunosorbent assay (ELISA) in rheumatoid arthritis and systemic lupus erythematosus. Collagen Rela. Res 2:557–561Google Scholar
  24. 24.
    Ellingsworth LR, DeLustro F, Brennan JE, Sawamura S, McPherson J (1986) The human immune response to reconstituted bovine collagen. J Immunol 136:877–882PubMedGoogle Scholar
  25. 25.
    Trentham DE, Townes AS, Kang AH (1977) Autoimmunity to type II collagen: an experimental model of arthritis. J Exp Med 146:857–869PubMedCrossRefGoogle Scholar
  26. 26.
    Rowley M, Tait B, Mackay IR, Cunningham T, Phillips B (1986) Collagen antibodies in rheumatoid arthritis. Significance of antibodies to denatured collagen and their association with HLA-DR4. Arthritis Rheum 29:174PubMedCrossRefGoogle Scholar
  27. 27.
    Buckee C, Morgan K, Ayad S, Collins I, Clague RB, Holt PJL (1990) Diversity of antibodies to type II collagen in patients with rheumatoid arthritis: detection by binding to a-chains and to cyanogen bromide peptides. Br J Rheumatol 29:254–258PubMedCrossRefGoogle Scholar
  28. 28.
    Cook AD, Rowley MJ, Stockman A, Muirden KD, Mackay IR (1994) Specificity of antibodies to type II collagen in early rheumatoid arthritis. J Rheumatol (In Press)Google Scholar
  29. 29.
    Terato K, Shimozuru Y, Katayama K, Takemitsu Y, Yamshita I, Mitayatsu M, Fujii K, Sagara M, Kobayashi S, Goto M, Nishioka K, Miyasaka N, Nagai Y (1990) Specificity of antibodies to type II collagen in rheumatoid arthritis. Arthritis Rheum 33:1493–1500PubMedCrossRefGoogle Scholar
  30. 30.
    Worthington J, Turner S, Brass A, Morgan K (1993). Epitopes on the CB-11 peptide of type II collagen recognized by antibodies from patients with rheumatoid arthritis. Br J Rheumatol 32:658–662PubMedCrossRefGoogle Scholar
  31. 31.
    Terato K, Arai H, Shimozuru Y, Fukada T, Tanaka H, Watanabe H, Nagai Y, Fijimoto K, Okubo F,. Cho F, Hongjo S, Cremer MA (1989) Sex-linked differences in susceptibility of cynomolgus monkeys to type II collagen-induced arthritis. Arthritis Rheum 32:748–754PubMedCrossRefGoogle Scholar
  32. 32.
    Cremer MA, Terato K, Watson EC, Griffiths MM, Townes AS, Kang AH (1992) Collagen-induced arthritis in rats. J Immunol 149:1045–1053PubMedGoogle Scholar
  33. 33.
    Wener MH, Uwatoko S, Mannik M (1989) Antibodies to the collagen-like of Clq in sera of patients with autoimmune rheumatic diseases. Arthritis Rheum 32:544–551PubMedCrossRefGoogle Scholar
  34. 34.
    Arkles B, Redinger P (1983) Silicones in biomedical applications. In: Biocompatible Polymers, Metals, and Composities. Szycher M, Ed. Technomic Publishing, Lancaster, PA, USA 749–768Google Scholar
  35. 35.
    Picha GJ, Goldstein JA (1991) Analysis of the soft-tissue response to components used in the manufacture of breast implants: Rat animal model. Plast Reconstr Surg 87:490–500PubMedCrossRefGoogle Scholar
  36. 36.
    Mancino D, Bevilacqua, N (1977) Adjuvant effect of amorphous silica on the immune response to various antigens in guinea pigs. Int Arch Allergy Appl Immunol 53:97–103PubMedCrossRefGoogle Scholar
  37. 37.
    Weisman MH, Vecchione TF, Albert D, Moore LT, Mueller MR (1988) Connective-tissue disease following breast augmentation: a preliminary test of the human adjuvant disease hypothesis. Plast Reconstr Surg 82:626–630PubMedCrossRefGoogle Scholar
  38. 38.
    Gabriel SE, Melton JE, Woods JE, O’Fallon WM, Kurland LT (1993) Silicone-containing breast implants and connective tissue diseases: a population-based retrospective cohort study. Arthritis Rheum 36:S70CrossRefGoogle Scholar
  39. 39.
    Tenenbaum SA, Silveira LH, Martinez-Osuna P, Cuellar ML, Garry RF, Espinoza LR (1992) Identification of a novel autoantigen recognized in silicone-associated connective tissue disease. Arthritis Rheum. 35:S73CrossRefGoogle Scholar
  40. 40.
    Bridges AJ, Lorden T (1993) Sicca syndrome in women with silicone implants: absence of serum autoantibodies. Arthritis Rheum 36.S70CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • M. J. Rowley
    • 1
  • A. D. Cook
    • 1
  • I. R. Mackay
    • 1
  • S. S. Teuber
    • 2
    • 3
  • M. E. Gershwin
    • 2
  1. 1.Centre for Molecular Biology and MedicineMonash UniversityClaytonAustralia
  2. 2.Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical ImmunologyUniversity of California at Davis, School of MedicineDavisUSA
  3. 3.Department of Veterans Affairs Northern California System of ClinicsPleasant HillUSA

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