Advertisement

Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

New Goals for Immunosuppressive Therapy in Autoimmune Diseases

  • 4 Accesses

  • 3 Citations

Summary

Current immunosuppressive therapy of autoimmune disease is frequently hampered by insufficient response to treatment, relapse at cessation of treatment and adverse effects of therapy such as toxicity and over-immunosuppression. These difficulties will be overcome by treating diseases earlier in their natural history, before the autoimmune response has become irreversible.

At this early stage of treatment only drugs with low toxicity should be used. Present hopes rely more on monoclonal antibodies than on chemical immunosuppressants that could substitute for the reference drugs cyclosporin (in T cell-mediated disease) and cyclophosphamide (in antibody-mediated disease). However, only a few monoclonal antibodies are presently available, and the possibility of using them for long term treatment is still under investigation.

Undoubtedly the final goal for treatment of autoimmune disease is to restore broken-down tolerance to self antigens, perhaps by combining administration of monoclonal antibodies and soluble autoantigen or by oral administration of the autoantigen. This strategy requires, however, that the target autoantigen of each autoimmune disease is identified. At present this is the case for very few diseases.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Feutren G. The use of cyclosporin in autoimmune diseases. In: Bach JF, editor. T-cell-directed immunointervention. Oxford: Blackwell Scientific Publications, 1993: 101–18

  2. 2.

    Bach JF. Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr Rev. In press

  3. 3.

    Bach JF. Immunosuppressive therapy of autoimmune diseases. Immunol Today 1993; 14: 213–6

  4. 4.

    Bach JF, Strom TB, editors. The mode of action of immunosuppressive agents. Amsterdam: Elsevier, 1985

  5. 5.

    Schreiber SL, Crabtree GR. The mechanism of action of cyclosporin A and FK506. Immunol Today 1992; 13: 136–42

  6. 6.

    Thomson AW, Carroll PB, McCauley J, et al. FK506: a novel immunosuppressant for treatment of autoimmune disease. Springer Semin Immunopathol 1993; 14: 323–44

  7. 7.

    Kreis H, Dubernard JM, editors. New immunosuppressive drugs. Transpl Proc 1993; 25: 619–844

  8. 8.

    Feutren G, Mihatsch MJ. Risk factors of cyclosporine-induced nephropathy in patients with autoimmune diseases. New Engl J Med 1992; 326: 1654–60

  9. 9.

    Swinnen LJ, Costanzo-Nordin MR, Gisher SG, et al. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardic-transplant recipients. New Engl J Med 1990; 323: 1723–8

  10. 10.

    Goodnow CC. Cellular mechanisms of self-tolerance. Curr Opin Immunol 1989; 2: 226–36

  11. 11.

    Miller JFAP, Morahan G. Peripheral T cell tolerance. Annu Rev Immunol 1992; 10: 59–69

  12. 12.

    Weiner HL, Miller A, Khoury SJ, et al. Suppression of organ-specific autoimmune diseases by oral administration of autoantigens. In: Gergely J, et al., editors. Progress in immunology VIII. Proceedings of the 8th International Congress of Immunology; 1992 August; Budapest, 1993: 627–34

  13. 13.

    Zhang JZ, Dabidson L, Eisenbarth G, et al. Suppression of diabetes in NOD mice by oral administration of porcine insulin. Proc Natl Acad Sci USA 1991; 88: 10252–6

  14. 14.

    Weiner HL, Mackin GA, Matsui M, et al. Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis. Science 1993; 259: 1321–4

  15. 15.

    Trentham DE, Dynesius-Trentham RA, Orav EJ, et al. Effects of oral administration of type II collagen on rheumatoid arthritis. Science 1993; 261: 1727–30

  16. 16.

    Rayner DC, Champion BR, Cooke A. Thyroglobulin as autoantigen and tolerogen. In: Bach JF, editor. Monoclonal antibody and peptide therapy in autoimmune diseases. New York: Marcel Dekker, 1993: 359–76

  17. 17.

    Elias D, Markovits D, Reshef T, et al. Induction and therapy of autoimmune diabetes in the non-obese diabetic (NOD/Lt) mouse by a 65-kDa heat shock protein. Proc Natl Acad Sci USA 1990; 87: 1576–80

  18. 18.

    Borel Y. Natural immunologic tolerance and the construction of tolerogens to treat autoimmune diseases. In: Ishizaka K, Jackson REL, editors. Concepts in Immunology. Basel: Karger, 1989: 145–61

  19. 19.

    Koevary SB, Blomberg M. Prevention of diabetes in BB/Wor rats by intrathymic islet injection. J Clin Invest 1992; 89: 512–6

  20. 20.

    Tisch R, Yang XD, Singer SM, et al. Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature 1993; 366: 72–5

  21. 21.

    Wraith DC. Autoantigenic peptide therapy in experimental autoimmune encephalomyelitis. In: Bach JF, editor. Monoclonal antibody and peptide therapy in autoimmune diseases. New York: Marcel Dekker, 1993: 345–57

  22. 22.

    Rothbard JB, McDevitt HO. Use of MHC antagonists to prevent and treat autoimmune disease in animal models. In: Bach JF, editor. T-cell—directed immunointervention. Oxford: Blackwell Scientific Publications, 1993: 286–99

  23. 23.

    Shizuru JA, Alters SE, Fathman CG. Anti-CD4 monoclonal antibodies in therapy: creation of nonclassical tolerance in the adult. Immunol Rev 1992; 129: 105–30

  24. 24.

    Cobbold SP, Qin S, Leong LYW, et al. Reprogramming the immune system for peripheral tolerance with CD4 and CD8 monoclonal antibodies. Immunol Rev 1992; 129: 165–201

  25. 25.

    Hutchings P, O’Reilly L, Parish NM, et al. The use of non-depleting anti-CD4 monoclonal antibody to re-establish tolerance to cells in NOD mice. Eur J Immunol 1992; 22: 1913–8

  26. 26.

    Chatenoud L, Thervet E, Primo J, et al. Ami-CD3 antibody induces long-term remission of overt autoimmunity in non-obese diabetic mice. Proc Natl Acad Sci USA. In press

  27. 27.

    Wood ML, Monaco AP, Gozzo JJ, et al. Use of homozygous allogeneic bone marrow for induction of tolerance with anti-lymphocyte serum: dose and timing. Transplant Proc 1970; 3: 676–9

  28. 28.

    Nicolls MR, Aversa GG, Pearce NW, et al. Induction of long term specific tolerance to allografts in rats by therapy with an anti-CD3-like monoclonal antibody. Transplantation 1993; 55: 459–68

Download references

Author information

Correspondence to Dr. Jean-Francois Bach.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bach, J. New Goals for Immunosuppressive Therapy in Autoimmune Diseases. Clin. Immunother. 1, 95–100 (1994). https://doi.org/10.1007/BF03258495

Download citation

Keywords

  • Autoimmune Disease
  • Major Histocompatibility Complex
  • FK506
  • Mycophenolic Acid
  • Obese Diabetic Mouse