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The Structure of a Human Rheumatoid Factor Bound to IgG Fc

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Glycoimmunology 2

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 435))

Abstract

Rheumatoid factors (RF) are autoantibodies with reactivity towards the Fc regions of IgG molecules (1). They are found in the sera and synovia of most patients with rheumatoid arthritis (RA), and high levels of RF are associated with severe disease and poor prognosis (2,3) suggesting that they have a causative role in the pathology of this disease. The IgM or IgG RFs form immune complexes with IgG molecules in the joints, which can then activate complement and cause inflammation. However, not all RFs cause disease, and the distinction between “pathological” and “physiological” RFs is not understood (4).

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References

  1. Tighe, H. & Carson, D.A. Rheumatoid Factor. In Textbook of Rheumatology (Kelley, W.N., Harris, E.D., Ruddy, S. & Sledge, C.B. eds.) W.B. Saunders, Philadelphia, pp 241–249, 1997.

    Google Scholar 

  2. Zvaifler, N.J. The immunopathology of joint inflammation in rheumatoid arthritis. Adv. Immunol., 16, 265–336, 1973.

    Article  PubMed  CAS  Google Scholar 

  3. Vaughan, J.H. Pathogenetic concepts and origins of rheumatoid factor in rheumatoid arthritis. Arthritis Rheum., 36, 1–6, 1993.

    Article  PubMed  CAS  Google Scholar 

  4. Chen, P.P. & Carson, D.A. New insights on the physiological and pathological rheumatoid factors in humans. In Autoimmunity: Physiology and Disease (Coutinho, A. & Kazatchkine, M., eds.) Wiley-Liss, New York, pp 247–266, 1994.

    Google Scholar 

  5. Olee, T., Lu, E.W., Huang, D-F. et al. Genetic analysis of self-associating IgG rheumatoid factors from two rheumatoid synovia implicates an antigen-driven response. J. Exp. Med., 175, 831–842, 1992.

    Article  PubMed  CAS  Google Scholar 

  6. Randen, I., Thompson, K.M., Pascual, V. et al. Rheumatoid factor V genes from patients with rheumatoid arthritis are diverse and show evidence of an antigen-driven response. Immunol. Rev., 128, 49–71, 1992.

    Article  PubMed  CAS  Google Scholar 

  7. Ermel, R.W., Kenny, T.P., Chen, P.P. & Robbins, D.L. Molecular analysis of rheumatoid factors derived from rheumatoid synovium suggests an antigen-driven response in inflamed joints. Arthritis Rheum., 36, 380–388, 1993.

    Article  PubMed  CAS  Google Scholar 

  8. Bonagura, V.R., Artandi, S.E., Davidson, A. et al. Mapping studies reveal unique epitopes on IgG recognised by rheumatoid arthritis-derived monoclonal rheumatoid factors. J. Immunol, 151, 3840–3852, 1993.

    PubMed  CAS  Google Scholar 

  9. Artandi, S.E., Calame, K.L., Morrison, S.L. & Bonagura, V.R. Monoclonal IgM rheumatoid factors bind IgG at a discontinuous epitope comprised of amino acid loops from heavy-chain constant-region domains 2 and 3. Proc. Natl. Acad, Sci. USA, 89, 94–98, 1992.

    Article  CAS  Google Scholar 

  10. Peterson, C., Malone, C.C. & Williams, R.C. Rheumatoid-factor-reactive sites on CH3 established by overlapping 7-mer peptide epitope analysis. Mol. Immunol, 32, 57–75, 1995.

    Article  PubMed  CAS  Google Scholar 

  11. Steinitz, M., Izak, G., Cohen, S., Ehrenfeld, M. & Flechner, J. Continuous production of monoclonal rheumatoid factor by EBV-transformed lymphocytes. Nature, 287, 443–445, 1980.

    Article  PubMed  CAS  Google Scholar 

  12. Steinitz, M. & Tamir, S. Human monoclonal autoimmune antibody produced in vitro: rheumatoid factor generated by Epstein-Barr virus-transformed cell line. Eur. J. Immunol, 12, 126–133, 1982.

    Article  PubMed  CAS  Google Scholar 

  13. Pascual, V., Victor, K., Randen, I., Thompson, K., Steinitz, M., Forre, O., Fu, S-M., Natvig, J.B. & Capra, J.D. Nucleotide sequence analysis of rheumatoid factors and polyreactive antibodies derived from patients with rheumatoid arthritis reveals diverse use of VH and VL gene segments and extensive variability in CDR-3. Scand. J. Immunol, 36, 349–362, 1992.

    Article  PubMed  CAS  Google Scholar 

  14. Sohi, M.K., Corper, A.L., Wan, T., Steinitz, M., Jefferis, R., Beale, D., He, M., Feinstein, A., Sutton, B.J. & Taussig, M.J. Crystallization of a complex between the Fab fragment of a human immunoglobulin M (IgM) rheumatoid factor (RF-AN) and the Fc fragment of human IgG4 Fc. Immunology, 88, 636–641, 1996.

    Article  PubMed  CAS  Google Scholar 

  15. Jefferis, R., Lund, J., Mizutani, H., Nakagawa, H., Kawazoe, Y., Arata, Y. & Takahashi, N. A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins. Biochem. J. 268, 529–537, 1990.

    PubMed  CAS  Google Scholar 

  16. Parekh, R.B., Dwek, R.A., Sutton, B.J. et al. Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature, 316, 452–457, 1985.

    Article  PubMed  CAS  Google Scholar 

  17. Rahman, M.A.A. & Isenberg, D.A. Glycosylation of IgG in rheumatic disease. In Abnormalities of IgG Glycosylation and Immunological Disorders (Isenberg, D.A. & Rademacher, T.W. eds.) John Wiley & Sons Ltd., pp 101–118, 1996.

    Google Scholar 

  18. Parekh, R.B., Roitt, I.M., Isenberg, D.A., Dwek, R.A., Ansell, B.M. & Rademacher, T.W. Galactosylation of IgG associated oligosaccharides: reduction in patients with adult and juvenile onset rheumatoid arthritis and relation to disease activity. Lancet, i, 966–969, 1988.

    Article  Google Scholar 

  19. Corper, A.L., Sohi, M.K., Bonagura, V.R., Steinitz, M., Jefferis, R., Feinstein, A., Beale, D., Taussig, M.J. & Sutton, B.J. Structure of a human IgM rheumatoid factor in complex with its autoantigen IgG Fc. Nature Struct. Biol., in press, 1997.

    Google Scholar 

  20. Davies, D.R. & Cohen, G.H. Interactions of protein antigens with antibodies. Proc. Natl Acad. Sci. USA, 93, 7–12, 1996.

    Article  PubMed  CAS  Google Scholar 

  21. Fields, B.A., Goldbaum, F.A., Ysern, X., Poljac, R.J. & Mariuzza, R.A. Molecular basis of antigen mimicry by an anti-idiotope. Nature, 374, 739–742, 1995.

    Article  PubMed  CAS  Google Scholar 

  22. Sheriff, S. Some methods for examining the interactions between two molecules. Immunomethods, 3, 191–196, 1993.

    Article  CAS  Google Scholar 

  23. Kabat, E.A., Wu, T.T., Perry, H.M., Gottesman, K.S. & Foeler, C. Sequences of Proteins of Immunological Interest. US Department of Health and Human Services, NIH, Bethesda, MD, USA, 1991.

    Google Scholar 

  24. Deisenhofer, J. Crystallographic refinement and atomic models of a human Fc fragment and its complex with fragment B of protein A from Staphylococcus aureus at 2.9-and 2.8-Å resolution. Biochemistry, 20, 2361–2370, 1981.

    Article  PubMed  CAS  Google Scholar 

  25. Sutton, B.J. & Phillips, D.C. The three-dimensional structure of the carbohydrate within the Fc fragment of IgG. Biochem. Soc. Trans., 11, 130–132, 1983.

    CAS  Google Scholar 

  26. Malhotra, R., Wormald, M.R., Rudd, P.M., Fischer P.B., Dwek, R.A. & Sim, R.B. Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-binding protein. Nature Medicine, 1, 237–243, 1995.

    Article  PubMed  CAS  Google Scholar 

  27. Gilhespy-Muskett, A.M., Partridge, J., Jefferis, R. & Homans, S.W. A novel 13C isotopic labelling strategy for probing the structure and dynamics of glycan chains in situ on glycoproteins. Glycobiology, 4, 485–489, 1994.

    Article  PubMed  CAS  Google Scholar 

  28. Roitt, I.M., Dwek, R.A., Parekh, R.B. et al. Changes in carbohydrate structure of IgG in rheumatoid arthritis. Recenti Prog. Medicina, 79, 314–317, 1988.

    CAS  Google Scholar 

  29. Soltys, A.J., Hay, F.C., Bond, A., Axford, J.A., Jones, M.G., Randen, I., Thompson, K.M. & Natvig, J.B. The binding of synovial tissue-derived human monoclonal immunoglobulin M rheumatoid factor to immunoglobulin G preparations of differing galactose content. Scand. J. Immunol. 40, 135–143, 1994.

    Article  PubMed  CAS  Google Scholar 

  30. Soltys, A.J., Bond, A., Westwood, O.M.R. & Hay, F.C. The effects of altered glycosylation of IgG on rheumatoid factor-binding and immune complex formation. In Glycoimmunology (Alavi, A & Axford J.S., eds.), Plenum Press, New York, Adv. Exp. Med. Biol., 376, 155–160, 1995.

    Chapter  Google Scholar 

  31. Newkirk, M. Fc glycosylation and rheumatoid factors. In Abnormalities of IgG Glycosylation and Immunological Disorders (Isenberg, D.A. & Rademacher, T.W. eds.) John Wiley & Sons Ltd., pp 119–130, 1996.

    Google Scholar 

  32. Newkirk, M.M., Fournier, M-J. & Shiroky, J. Rheumatoid factor avidity in patients with rheumatoid arthritis: identification of pathogenic RFs which correlate with disease parameters and with the Gal(0) glycoform of IgG. J. Clin. Immunol., 15, 250–257, 1995.

    Article  PubMed  CAS  Google Scholar 

  33. Jefferis, R., Nik Jaafer, M.I. & Steinitz, M. Immunogenic and antigenic epitopes of immunoglobulins. VIII. A human monoclonal rheumatoid factor having specificity for a discontinuous epitope determined by histidine/arginine interchange at residue 435 of immunoglobulin G. Immunol. Lett., 7, 191–194, 1984.

    Article  PubMed  CAS  Google Scholar 

  34. Sauer-Eriksson, A.E., Kleywegt, G.J., Uhlen, M. & Jones, T.A. Crystal structure of the C2 fragment of streptococcal protein G in complex with the Fc domain of human IgG. Structure, 3, 265–278, 1995.

    Article  PubMed  CAS  Google Scholar 

  35. Burmeister, W.P., Huber, A.H. & Bjorkman, P.J. Crystal structure of the complex of rat neonatal Fc receptor with Fc. Nature, 372, 379–383, 1994.

    Article  PubMed  CAS  Google Scholar 

  36. Oppliger, I.R., Nardella, F.A., Stone, G.C. & Mannik, M. Human rheumatoid factors bear the internal image of the Fc binding region of Staphylococcal protein A. J. Exp. Med., 166, 702–710, 1987.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. The Randall Institute, King’s College London, 26-29 Drury Lane, London, WC2B 5RL, UK

    Brian J. Sutton, Adam L. Corper & Maninder K. Sohi

  2. Department of Immunology, The Medical School, University of Birmingham, Birmingham, B15 2TT, UK

    Roy Jefferis

  3. Department of Immunology, The Babraham Institute, Babraham, Cambridge, CB2 4AT, UK

    Dennis Beale & Michael J. Taussig

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  1. Brian J. Sutton
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  2. Adam L. Corper
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  3. Maninder K. Sohi
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  4. Roy Jefferis
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  5. Dennis Beale
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  6. Michael J. Taussig
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  1. St. George’s Hospital Medical School, University of London, London, UK

    John S. Axford

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Sutton, B.J., Corper, A.L., Sohi, M.K., Jefferis, R., Beale, D., Taussig, M.J. (1998). The Structure of a Human Rheumatoid Factor Bound to IgG Fc. In: Axford, J.S. (eds) Glycoimmunology 2. Advances in Experimental Medicine and Biology, vol 435. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5383-0_4

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  • DOI: https://doi.org/10.1007/978-1-4615-5383-0_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7457-2

  • Online ISBN: 978-1-4615-5383-0

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