Skip to main content
Log in

Vaccination Against Rheumatoid Arthritis

Concepts and Progress

  • Leading Article
  • Published:
BioDrugs Aims and scope Submit manuscript

Summary

Recently, interest has grown in the potential benefit of vaccination approaches in humans with rheumatoid arthritis. Approaches evaluated include the use of T cell receptor peptide vaccines, autologous T cells, major histocompatibility complex (MHC) peptides, allogeneic mononuclear cells and oral collagen.

The use of T cell receptor peptide vaccination in rheumatoid arthritis has been limited to dose-finding and pharmacokinetic studies with Vβ14 and Vβ17 peptides. The results of an ongoing placebo-controlled clinical trial with a combination of Vβ3, Vβ14 and Vβ17 peptides will be of interest.

Since the pathogenic T cells in rheumatoid arthritis are not known, the use of mixed T cell populations for attenuated autologous T cell vaccination may be necessary. This approach has been evaluated in a small number of patients. Significant clinical or adverse effects were not observed. The appropriate dose, route of administration and method of attenuation of autologous T cells remains to be more clearly defined. In addition, any immunisation approach that targets T cells that are not pathogenic has the potential of immunising against beneficial T cell clones.

Rheumatoid arthritis is associated with certain MHC class II alleles (e.g. HLA-DR1 and DR4). Rheumatoid arthritis frequently remits during pregnancy, although the mechanisms associated with this are not clear. Based on this observation, several therapeutic approaches have been evaluated in rheumatoid arthritis. These include placenta-eluted gamma globulins (which contain antibodies to HLA-DR antigens), DR4/DR1 peptide vaccines and allogeneic mononuclear cell vaccination. In uncontrolled trials, each of these approaches has been shown to have no adverse effects and encouraging clinical benefits have been observed, although double-blind placebo-controlled studies will be needed to assess these approaches.

Encouraging clinical results have been reported to date with oral administration of type II collagen as a therapy for rheumatoid arthritis, and large multicentre controlled trials are currently under way.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Harris ED. Rheumatoid arthritis: pathophysiology and implications for therapy. N Engl J Med 1990; 322: 1277–89

    Article  PubMed  Google Scholar 

  2. Koopman WJ, Gay S. Do nonimmunologically mediated pathways play a role in the pathogenesis of rheumatoid arthritis?. Rheum Dis Clin North Am 1993; 19: 107–22

    PubMed  CAS  Google Scholar 

  3. Moreland LW, Koopman WJ. Biologic agents as potential therapies for treatment of autoimmune disease. In: Koopman WJ, editor. Arthritis and allied conditions. 13th ed. Baltimore: Williams and Wilkins, 1997; 777–809

    Google Scholar 

  4. Happ MP, Kiraly A, Offner H et al. The autoreactive T-cell population in EAE: TCR β chain rearrangements. J Neuroimmunol 1988; 19: 191–9

    Article  PubMed  CAS  Google Scholar 

  5. Burns FR, Li X, Shen N et al. Both rat and mouse T-cell receptors specific for the encephalitogenic determinant of myelin basic protein use similar Vα and Vβ chain genes even though the major histocompatibility complex and encephalitogenic determinants being recognized are different. J Exp Med 1989; 169: 27–39

    Article  PubMed  CAS  Google Scholar 

  6. Urban JL, Kumar V, Kono DH et al. Restricted use of T-cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell 1988; 54: 577–92

    Article  PubMed  CAS  Google Scholar 

  7. Acha-Orbea H, Mitchell DJ, Timmermann L et al. Limited heterogeneity of T-cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell 1988; 54: 263–73

    Article  PubMed  CAS  Google Scholar 

  8. Bourdette DN, Whitham RH, Chou YK et al. Immunity to TCR peptides in multiple sclerosis. I. Successful immunization of patients with synthetic Vβ5.2 and Vβ6.1 CDR 2 peptides. J Immunol 1994; 152: 2510–9

    PubMed  CAS  Google Scholar 

  9. Lider O, Karin N, Shinitsky M et al. Therapeutic vaccination against adjuvant arthritis using autoimmune T-cells treated with hydrostatic pressure. Proc Natl Acad Sci USA 1987; 84: 4577–80

    Article  PubMed  CAS  Google Scholar 

  10. Mor F, Lohse AW, Karin N et al. Clinical modeling of T-cell vaccination against autoimmune disease in rats: selection of antigen-specific T-cells using a mitogen. J Clin Invest 1990; 85: 1594–8

    Article  PubMed  CAS  Google Scholar 

  11. Gustafsson K, Karlsson M, Anderson L et al. Structures on the I-A molecule predisposing for susceptibility to type II collagen-induced autoimmune arthritis. Eur J Immunol 1990; 20: 2127–31

    Article  PubMed  CAS  Google Scholar 

  12. Yoshino S, Yoshino J. Suppression of chronic antigen-induced arthritis in rats by a monoclonal antibody against the T-cell receptor aβ. Cell Immunol 1992; 144: 382–91

    Article  PubMed  CAS  Google Scholar 

  13. Rosloniec EF, Brand DD, Whittington KB et al. Vaccination with a recombinant Vα domain of a TCR presents the development of collagen-induced arthritis. J Immunol 1995; 155: 4504–11

    PubMed  CAS  Google Scholar 

  14. Zagon G, Tumang JR, Li Y et al. Increased frequency of Vβ17positive T-cells in patients with rheumatoid arthritis. Arthritis Rheum 1994; 37: 1431–40

    Article  PubMed  CAS  Google Scholar 

  15. Goronzy JJ, Bartz-Bazzanella P, Hu W et al. Dominant clonotypes in the repertoire of peripheral CD4+ T-cells in rheumatoid arthritis. J Clin Invest 1994; 94: 2068–76

    Article  PubMed  CAS  Google Scholar 

  16. Paliard X, West S, Lafferty J et al. Evidence for the effects of a superantigen in rheumatoid arthritis. Science 1991; 253: 325–9

    Article  PubMed  CAS  Google Scholar 

  17. Bucht A, Oksenberg JR, Lindblad S et al. Characterization of T-cell receptor β repertoire in synovial tissue from different temporal phases of rheumatoid arthritis. Scand J Immunol 1992; 35: 159–65

    Article  PubMed  CAS  Google Scholar 

  18. Jenkins RN, Nikaein A, Zimmermann A et al. T cell receptor Vβ gene bias in rheumatoid arthritis. J Clin Invest 1993; 92: 2688–701

    Article  PubMed  CAS  Google Scholar 

  19. Williams WV, Fang Q, Demarco D et al. Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium. J Clin Invest 1992; 90: 326–33

    Article  PubMed  CAS  Google Scholar 

  20. Howell MD, Diveley JP, Lundeen KA et al. Limited T-cell receptor B-chain heterogeneity among interleukin 2 receptorpositive synovial T cells suggests a role for superantigen in rheumatoid arthritis. Proc Natl Acad Sci USA 1991; 88: 10921–5

    Article  PubMed  CAS  Google Scholar 

  21. Stamenkovic I, Stegagno M, Wright KA et al. Clonal dominance among T-lymphocyte infiltrates in arthritis. Proc Natl Acad Sci USA 1988; 85: 1179–83

    Article  PubMed  CAS  Google Scholar 

  22. Cooper SM, Dier DL, Roessner KD et al. Diversity of rheumatoid synovial tissue T cells by T cell receptor analysis: oligoclonal expansion in interleukin-2 responsive cells. Arthritis Rheum 1991; 34: 537–46

    Article  PubMed  CAS  Google Scholar 

  23. Miltenburg AMM, Van Laar JJ, Daha MR et al. Dominant T- cell receptor β-chain gene rearrangements indicate clonal expansion in the rheumatoid joint. Scand J Immunol 1990; 31: 121–5

    Article  PubMed  CAS  Google Scholar 

  24. Duby AD, Sinclair AK, Osborae-Lawrence SL et al. Clonal heterogeneity of synovial fluid T lymphocytes from patients with rheumatoid arthritis. Proc Natl Acad Sci USA 1989; 86: 6206–10

    Article  PubMed  CAS  Google Scholar 

  25. Uematsu Y, Wege H, Straus A et al. The T-cell-receptor repertoire in the synovial fluid of a patient with rheumatoid arthritis is polyclonal. Proc Natl Acad Sci USA 1991; 88: 8534–8

    Article  PubMed  CAS  Google Scholar 

  26. Sottini A, Imberti L, Goria R et al. Restricted expression of T cell receptor Vβ but not Va genes in rheumatoid arthritis. Eur J Immunol 1991; 253: 325–9

    Google Scholar 

  27. Grom AA, Thompson SD, Luyrink L et al. Dominant T-cell receptor β chain variable region Vβ14+ clones in juvenile rheumatoid arthritis. Proc Natl Acad Sci USA 1993; 90: 11104–8

    Article  PubMed  CAS  Google Scholar 

  28. Korthauer U, Hennerkes B, Menninger H et al. Oligoclonal T cells in rheumatoid arthritis: identification strategy and molecular characterization of a clonal T-cell receptor. Scand J Immunol 1992; 36: 855–63

    Article  PubMed  CAS  Google Scholar 

  29. Lunardi C, Marguerie C, So AK. An altered repertoire of T cell receptor V gene expression by rheumatoid synovial fluid T lymphocytes. Clin Exp Immunol 1992; 90: 440–6

    Article  PubMed  CAS  Google Scholar 

  30. Cooper SM, Roessner KD, Naito-Hoopes M et al. Increased usage of Vβ2 and Vβ6 in rheumatoid synovial fluid T cells. Arthritis Rheum 1994; 37: 1627–36

    Article  PubMed  CAS  Google Scholar 

  31. Pluschke G, Ricken G, Taube H et al. Biased T cell receptor Va region repertoire in the synovial fluid of rheumatoid arthritis patients. Eur J Immunol 1991; 21: 2749–54

    Article  PubMed  CAS  Google Scholar 

  32. Der Simonian H, Sugita M, Glass DN et al. Clonal Vα12.1+ T cell expansions in the peripheral blood of rheumatoid arthritis patients. J Exp Med 1993; 177: 1623–31

    Article  Google Scholar 

  33. Bröker BM, Korthäuer U, Heppt P et al. Biased T cell receptor V gene usage in rheumatoid arthritis: oligoclonal expansion of T cells expressing Vα2 genes in synovial fluid but not in peripheral blood. Arthritis Rheum 1993; 36: 1234–43

    Article  PubMed  Google Scholar 

  34. Williams WV, Kieber-Emmons T, Fang Q et al. Conserved motifs in rheumatoid arthritis synovial tissue T-cell receptor beta chains. DNA Cell Biol 1993; 12: 425–34

    Article  PubMed  CAS  Google Scholar 

  35. Lamour A, Jouen-Beades F, Lees O et al. Analysis of T-cell receptors in rheumatoid arthritis: the increased expression of HLA-DR antigen on circulating gamma delta + T-cells is correlated with disease activity. Clin Exp Immunol 1992; 89: 217–22

    Article  PubMed  CAS  Google Scholar 

  36. Fischer D-C, Opalka B, Hoffman A et al. Limited heterogeneity of rearranged T-cell receptor Vα and Vβ transcripts in synovial fluid T-cells in early stages of rheumatoid arthritis. Arthritis Rheum 1996; 39: 454–62

    Article  PubMed  CAS  Google Scholar 

  37. Moreland LW, Heck Jr LW, Koopman WJ, et al. Vβ17 T-cell receptor peptide vaccine: results of a phase I dose-finding study in patients with rheumatoid arthritis. Ann NY Acad Sci 1995 Jul; 756: 211–4

    Article  PubMed  CAS  Google Scholar 

  38. van Laar JM, Miltenburg AMM, Verdonk MJA et al. Effects of inoculation with attenuated autologous T cells in patients with rheumatoid arthritis. J Autoimmun 1993; 6: 159–67

    Article  PubMed  Google Scholar 

  39. Kingsley GH, Verwilghen J. T-cell vaccinations in humans. Clin Exp Rheumatol 1993; 11: S63–4

    PubMed  Google Scholar 

  40. Lohse AW, Bakker NPM, Hermann E, et al. Induction of an anti-vaccine response by T-cell vaccination in non-human primates and humans. J Autoimmun 1993; 1(1): 121–30

    Article  Google Scholar 

  41. Weyand CM, Hicok KC, Conn DL et al. The influence of HLA- DRβl genes on disease severity in rheumatoid arthritis. Ann Intern Med 1992; 117: 801–6

    PubMed  CAS  Google Scholar 

  42. Nepom GT, Erlich H. MHC class-II molecules and autoimmu- nity. Annu Rev Immunol 1991; 9: 493–525

    Article  PubMed  CAS  Google Scholar 

  43. Winchester R. The molecular basis of susceptibility to rheumatoid arthritis. Adv Immunol 1994; 56: 389–466

    Article  PubMed  CAS  Google Scholar 

  44. Adelman NE, Watling DL, McDevitt HO. Treatment of (NZB/NZW) F1 disease with anti-I-A monoclonal antibodies. J Exp Med 1983; 158: 1350–5

    Article  PubMed  CAS  Google Scholar 

  45. Kramar G, Schurmans S, Aguado T et al. Anti-Ia treatment prevents lupus-like autoimmune syndrome in mice neonatally tolerized to alloantigens. J Autoimmun 1993; 6: 27–37

    Article  PubMed  CAS  Google Scholar 

  46. Wooley PH, Luthra HS, Lafuse WP et al. Type-II collagen-induced arthritis in mice: III. Suppression of arthritis by using monoclonal and polyclonal anti-Ia antisera. J Immunol 1985; 134: 2366–74

    PubMed  CAS  Google Scholar 

  47. Nelson JL. Maternal-fetal immunology and autoimmune disease: is some autoimmune disease auto-alloimmune or alloautoimmune? Arthritis Rheum 1996 Feb; 39: 191–4

    Article  PubMed  CAS  Google Scholar 

  48. Nelson JL, Hughes KA, Smith AG et al. Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced amelioration of rheumatoid arthritis. N Engl J Med 1993; 329: 466–71

    Article  PubMed  CAS  Google Scholar 

  49. Combe B, Cosso B, Clot J et al. Human placenta-eluted gammaglobulins in immunomodulating treatment of rheumatoid arthritis. Am J Med 1985; 78: 920–8

    Article  PubMed  CAS  Google Scholar 

  50. Sany J, Clot J, Bonneau M et al. Immunomodulating effect of human placenta-eluted gamma globulins in rheumatoid arthritis. Arthritis Rheum 1982; 25: 17–24

    Article  PubMed  CAS  Google Scholar 

  51. Moynier M, Cosso B, Brochier J et al. Identification of class II HLA alloantigens in placenta-eluted gammaglobulins used for treating rheumatoid arthritis. Arthritis Rheum 1987; 30: 375–81

    Article  PubMed  CAS  Google Scholar 

  52. Silverman ED, Lacer RM, Greenwald M et al. Intravenous gammaglobulin therapy in systemic juvenile rheumatoid arthritis. Arthritis Rheum 1990; 33: 1015–22

    Article  PubMed  CAS  Google Scholar 

  53. Jordan SC, Toyoda M. Treatment of autoimmune diseases and systemic vasculitis with pooled human intravenous immune globulin. Clin Exp Immunol 1994; 97 Suppl. 1:31–8

    PubMed  Google Scholar 

  54. Ruiz de Souza V, Kaveri SV, Kazatchkine MD. Intravenous immunoglobulin (IVIg) in the treatment of autoimmune and inflammatory diseases. Clin Exp Rheumatol 1993; 11 Suppl. 9: 533–6

    Google Scholar 

  55. Tumiati B, Casoli B, Veneziani M et al. High dose immunoglobulin therapy as an immunomodulatory treatment of rheumatoid arthritis. Arthritis Rheum 1992; 35: 1126–33

    Article  PubMed  CAS  Google Scholar 

  56. Kurlander RJ, Hall J. Comparison of intravenous gamma globulins and a monoclonal anti-Fc receptor antibody as inhibitors of immune clearance in vivo in mice. J Clin Invest 1986; 77: 2010–8

    Article  PubMed  CAS  Google Scholar 

  57. Sultan Y, Kazatchkine MD, Maisonneuve P, et al. Anti-idiotypic suppression of autoantibodies to Factor VIII (antihaemophilic factor) by high-dose intravenous gammaglobulin. Lancet 1984; II: 765–8

    Article  Google Scholar 

  58. Rossi F, Kazatchkine MD. Antiidiotypes against autoantibodies in pooled normal human polyspecific Ig. J Immunol 1989; 143: 4104–9

    PubMed  CAS  Google Scholar 

  59. Diutrich G, Kazatchkine MD. Normal immunoglobulin G (IgG) for therapeutic use (intravenous Ig) contain antiidiotypic specificities against an immunodominant, disease-associated, cross-reactive idiotype of human anti-thyroglobulin autoantibodies. J Clin Invest 1990; 85: 620–5

    Article  Google Scholar 

  60. Kaveri S, Vassilev T, Harez V et al. Antibodies to a conserved region of HLA class I molecules, capable of modulating CD8 T-cell mediated function, are present in pooled normal immunoglobulin for therapeutic use. J Clin Invest 1996; 97: 865–9

    Article  PubMed  CAS  Google Scholar 

  61. Marchalonis JJ, Kaymaz H, Dedeoglu F et al. Human autoantibodies reactive with synthetic autoantigens from T-cell receptor β chain. Proc Natl Acad Sci USA 1992; 89: 3325–9

    Article  PubMed  CAS  Google Scholar 

  62. Schifferli JA, Saurat JH, Didierjean L. Immunomodulatory effects of intravenous immunoglobulin G. J Rheumatol 1991; 18: 937–9

    PubMed  CAS  Google Scholar 

  63. Achiron A, Margalit R, Hershkoviz R et al. Intravenous immunoglobulin treatment of experimental T-cell mediated autoimmune disease: upregulation of T-cell proliferation and downregulation of tumour necrosis factor alpha secretion. J Clin Invest 1994; 93: 600–5

    Article  PubMed  CAS  Google Scholar 

  64. Hurez V, Kaveri SV, Mouhoub A et al. Anti-CD4 activity of normal human immunoglobulins G for therapeutic use (intravenous immunoglobulin, IVIg). Ther Immunol 1994; 1: 269–78

    PubMed  CAS  Google Scholar 

  65. Vassilev T, Gelin C, Kaveri SV et al. Antibodies to the CD5 molecule in normal human immunoglobulins for therapeutic use (intravenous immunoglobulins, IVIg). Clin Exp Immunol 1993; 92: 369–72

    Article  PubMed  CAS  Google Scholar 

  66. Fiocco U, Cozzi L, Cozzi E. Treatment of rheumatoid arthritis by murine antiidiotypic monoclonal antibodies to a syngeneic anti-HLA class II monoclonal antibody. Br J Rheumatol 1991; 30 Suppl.: 90–4

    Article  Google Scholar 

  67. Smith JB, Fort JG. Treatment of rheumatoid arthritis by immunization with mononuclear white blood cells: results of a preliminary trial. J Rheumatol 1996; 23 (2): 220–5

    PubMed  CAS  Google Scholar 

  68. Pratt W, Heck L, Moreland LW, et al. Safety and immunogenicity of a single intramuscular injection of a synthetic HLA-DR4/1 peptide vaccine with alum adjuvant in rheumatoid arthritis patients [abstract]. Arthritis Rheum 1995; 38 Suppl.: S281

    Google Scholar 

  69. Nagler-Anderson C, Bober LA, Robinson ME et al. Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen. Proc Natl Acad Sci USA 1986; 83: 7443–6

    Article  PubMed  CAS  Google Scholar 

  70. Thompson HSG, Staines NA. Gastric administration of type II collagen delays the onset and severity of collagen-induced arthritis in rats. Clin Exp Immunol 1986; 64: 581–6

    PubMed  CAS  Google Scholar 

  71. Zhang ZJ, Lee CSY, Lider O et al. Suppression of adjuvant arthritis in Lewis rats by oral administration of type II collagen. J Immunol 1990; 145: 2489–93

    PubMed  CAS  Google Scholar 

  72. Weiner HL, Friedman A, Miller A et al. Oral tolerance — immunologie mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of auto antigens. Annu Rev Immunol 1994; 12: 809–37

    Article  PubMed  CAS  Google Scholar 

  73. Trentham DE, Dynesius-Trentham RA, Orav EJ et al. Effects of oral administration of auto antigens. Annu Rev Immunol 1994; 12: 809–37

    Article  PubMed  Google Scholar 

  74. Sieper J, Kary S, Sörensen H et al. Oral type II collagen treatment in early rheumatoid arthritis: a double-blind, placebocontrolled, randomized trial. Arthritis Rheum 1996; 39: 41–51

    Article  PubMed  CAS  Google Scholar 

  75. Barnett ML, Combitchi D, Trentham DE. A pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritis. Arthritis Rheum 1996; 39: 623–8

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moreland, L.W., Koopman, W.J. Vaccination Against Rheumatoid Arthritis. BioDrugs 8, 87–95 (1997). https://doi.org/10.2165/00063030-199708020-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-199708020-00002

Keywords

Navigation