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Glycosylation of lgG during potentially arthritogenic lentiviral infections

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Abstract

Agalactosyl IgG [Gal(0)] was first discovered in patients with rheumatoid arthritis (RA). However, the proportion of this glycoform is also raised in tuberculosis and leprosy. This has helped reinforce the suggestion that RA may be triggered by a mycobacterium-like slow bacterial infection. On the other hand, arthritis can occur in mycobacterial diseases, so raised Gal(0) could be associated with a tendency to arthritis, rather than with a particular type of infection. Therefore, we wished to find out whether the percentage of Gal(0) [%Gal(0)] is increased in sheep and goats following infection with maedi visna virus or caprine arthritis encephalitis virus (CAEV), both of which can lead to inflammatory synovitis. We found that the normal level of Gal(0) in these species is much lower than in humans. Goats infected with CAEV or Mycobacterium paratuberculosis (used as a control mycobacterial infection) had a significant increase in %Gal(0), though it was still below the level seen in normal humans. Studies by Western blot confirmed the presence of terminal N-acetylglucosamine on heavy chains, and percentages of Gal(0) comparable to those seen in human RA could be generated by exposing goat IgG to streptococcal β-galactosidase. The rise in %Gal(0) was greatest in members of infected herds that were just starting to manifest arthritis, and tended to be lower in those in which severe carpitis had developed at the time of bleeding, implying the possibility that raised %Gal(0) may be an early or predisposing event for the development of arthritis. We found no rise in IgG antibody to the mycobacterial 65-kDa heat shock protein in goats with CAEV, distinguishing it from several other animal models of arthritis.

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References

  1. Parekh RB, Dwek RA, Sutton BJ, Fernandes DL, Leung A, Stanworth DR, Rademacher TW, Mizuochi T, Taniguchi T, Matsuta K, Takeuchi F, Nagano Y, Miyamoto T, Kobata A (1985) Association of rheumatoid arthritis and primary osteo-arthritis with changes in the glycosylation pattern of total serum IgG. Nature 316:452–457

    Google Scholar 

  2. Bodman KB, Sumar N, Mackenzie LE, Isenberg DA, Hay FC, Roitt IM, Lydyard PM (1992) Lymphocytes from patients with rheumatoid arthritis produce agalactosylated IgG in vitro. Clin Exp Immunol 88:420–423

    Google Scholar 

  3. Bahr GM, Yousof AM, Majeed HAM, Behbehani K, Lubani M, Parekh RB, Dwek RA, Rademacher TW, Young DB, Mehlert A, Steele J, Rook GAW (1990) Agalactosyl IgG, antibodies to heat shock proteins, and acute rheumatic fever. Ann Rheum Dis 49:383–386

    Google Scholar 

  4. Dube R, Rook GA, Steele J, Brealey R, Dwek R, Rademacher T, Lennard-Jones J (1990) Agalactosyl IgG in inflammatory bowel disease: correlation with C-reactive protein. Gut 31:431–434

    Google Scholar 

  5. O'Connor CM, Rook GAW, Fitzgerald MX (1992) Serum agalactosyl IgG levels in sarcoidosis. In: James G, Izumi T (eds) Proceedings of the World Conference on Sarcoidosis and other Granulomatous disease. Sarcoidosis 9 [Suppl 1]: 453–454

  6. Rademacher T, Parekh RB, Dwek RA, Isenberg D, Rook GAW, Axford JS, Roitt I (1988) The role of IgG glycoforms in the pathogenesis of rheumatoid arthritis. Springer Semin Immunopathol 10:231–249

    Google Scholar 

  7. Rook GAW, Onyebujoh P, Wilkins E, Ho Minh Ly, Al Attiyah R, Bahr GM, Corrah T, Hernandez H, Stanford JL (1994) A longitudinal study of % agalactosyl IgG in tuberculosis patients receiving chemotherapy, with or without immunotherapy. Immunology 81:149–154

    Google Scholar 

  8. Filley E, Andreoli A, Steele J, Waters M, Wagner D, Nelson D, Tung K, Rademacher T, Dwek R, Rook GAW (1989) A transient rise in agalactosyl IgG correlating with free IL-2 receptors during episodes of erythema nodosum leprosum. Clin Exp Immunol 76:343–347

    Google Scholar 

  9. Rook GAW, Lydyard PM, Stanford JL (1993) A reappraisal of the evidence that rheumatoid arthritis, and several other idiopathic diseases, are slow bacterial infections. Ann Rheum Dis 52 [Suppl]: S30-S38

    Google Scholar 

  10. Sumar N, Colaco CB, Bodman KB, Parekh R, Williams P, Dwek R, Rademacher TW, Isenberg DA, Soltys A, Hay FC, Roitt IM (1991) Abnormalities in the glycosylation of IgG in spouses of patients with rheumatoid arthritis. A familiy study. J Autoimmun 4:907–914

    Google Scholar 

  11. Tomana M, Schrohenloher RE, Reveille JD, Arnett FC, Koopman WJ (1992) Abnormal galactosylation of serum IgG in patients with systemic lupus erythematosus and members of families with high frequency of autoimmune disease. Rheumatol Int 12:191–194

    Google Scholar 

  12. Rook GAW, Stanford JL (1992) Slow bacterial infections or autoimmunity. Immunol Today 13:160–164

    Google Scholar 

  13. Harkiss GD (1994) Retroviral arthritis in animals and man. In: Panayi GS (ed) Immunology of connective tissue diseases. Immunology and Medicine. Kluwer Academic Publishers, pp 231–255

  14. Rook GAW, Steele J, Rademacher T (1988) A monoclonal antibody raised by immunising mice with group A streptococci binds to agalactosyl IgG from rheumatoid arthritis. Ann Rheum Dis 47:247–250

    Google Scholar 

  15. van Eden W (1991) Heat-shock proteins as immunogenic bacterial antigens with the potential to induce and regulate autoimmune arthritis. Immunol Rev 121:5–28

    Google Scholar 

  16. Rook GAW, Thompson S, Buckley M, Elson C, Brealey R, Lambert C, Whyte A, Rademacher TW (1991) The role of oil and agalatosyl IgG in the induction of arthritis in rodent models. Eur J Immunol 21:1027–1032

    Google Scholar 

  17. Bahr GM, Rook GAW, Al Saffar M, van Embden J, Stanford JL, Behbehani K (1988) Antibody levels to mycobacteria in relation to HLA type: evidence for non-HLA-linked high levels of antibody to the 65kDa heat shock protein of M. tuberculosis in rheumatoid arthritis. Clin Exp Immunol 74:211–215

    Google Scholar 

  18. Tsoulfa G, Rook GAW, Bahr G, Sattar MA, Young DB, Mehlert A, van Embden JDA, Hay F, Isenberg D, Lydyard PM (1988) Elevated IgG antibody level to the mycobacterial 65kDa heat shock protein are a characteristic of patients with rheumatoid arthritis. Scand J Immunol 30:519–527

    Google Scholar 

  19. Rademacher TW, Homans SW, Parekh RB, Dwek RA (1985) Immunoglobulin G as a glycoprotein. Biochem Soc Symp 51: 131–148

    Google Scholar 

  20. Sutton BJ, Phillips DC (1983) The three dimensional structure of the carbohydrate within the Fc fragment of immunoglobulin G. Biochem Soc Trans 11:130–132

    Google Scholar 

  21. Pepys MB, Rademacher TW, Amatayakul-Chantler S, Williams P, Noble GE, Hutchinson WL, Hawkins PN, Nelson SR, Gallimore JR, Herbert J, Hutton T, Dwek RA (1994) Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure. Proc Natl Acad Sci USA (in press)

  22. van Zeben D, Rook GAW, Hazes JMW, Zwinderman AH, Zhang Y, Ghelani S, Rademacher TW, Breedveld FC (1994) Early agalactosylation of IgG is associated with a more progressive disease course in patients with rheumatoid arthritis: results of a follow-up study. Br J Rheumatol 33:36–43

    Google Scholar 

  23. Parekh RB, Roitt IM, Isenberg DA, Dwek RA, Ansell BM, Rademacher TW (1988) Galactosylation of IgG associated oligosaccharides: reduction in patients with adult and juvenile onset rheumatoid arthritis and relation to disease activity. Lancet I:966–969

    Google Scholar 

  24. Tsuchiya N, Endo T, Matsuta K, Yoshinoya S, Aikawa T, Kosuge E, Takeuchi F, Myamoto T, Kobata A (1989) Effect of galactose depletion from oligosaccharide chains on immunological activities of human IgG. J Rheumatol 16:289–290

    Google Scholar 

  25. Tomana M, Schrohenloher RE, Bennett PH, del Puente A, Koopman WJ (1994) Occurrence of deficient galactosylation of serum IgG prior to onset of rheumatoid arthritis. Rheumatol Int 13:217–220

    Google Scholar 

  26. Rademacher TW, Williams P, Dwek RA (1994) Agalactosyl glycoforms of IgG autoantibodies are pathogenic. Proc Natl Acad Sci USA 91:6123–6127

    Google Scholar 

  27. Moreland LW, Koopman WJ (1991) Infection as a cause of arthritis. Curr Opin Rheumatol 3:639–649

    Google Scholar 

  28. Thompson SJ, Rook GAW, Brealey R, van-der-Zee R, Elson CJ (1990) Autoimmune reactions to heat shock proteins in pristane-induced arthritis. Eur J Immunol 20:2479–2484

    Google Scholar 

  29. Winfield J, Jarjour W (1991) Do stress proteins play a role in arthritis and autoimmunity. Immunol Rev 121:193–220

    Google Scholar 

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Authors and Affiliations

  1. Medical Microbiology, UCL Medical School, 67-73 Riding House Street, W1P 7PP, London, UK

    J. McCulloch, Y. W. Zhang & G. A. W. Rook

  2. Virology Discipline, Central Veterinary Laboratory, New Haw, Addlestone, Surrey, UK

    M. Dawson

  3. Department of Veterinary Pathology, Royal (Dick) School of Veterinary Studies, Summerhall, Edinburgh, UK

    G. D. Harkiss

  4. Institute of Veterinary Virology, University of Berne, Berne, Switzerland

    E. Peterhans & H. R. Vogt

  5. Department of Immunology, UCL Medical School, London, UK

    P. M. Lydyard

Authors
  1. J. McCulloch
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  2. Y. W. Zhang
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  3. G. A. W. Rook
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  4. M. Dawson
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  5. G. D. Harkiss
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  6. E. Peterhans
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  7. H. R. Vogt
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  8. P. M. Lydyard
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McCulloch, J., Zhang, Y.W., Rook, G.A.W. et al. Glycosylation of lgG during potentially arthritogenic lentiviral infections. Rheumatol Int 14, 243–248 (1995). https://doi.org/10.1007/BF00262090

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  • DOI: https://doi.org/10.1007/BF00262090

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