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Clinical Reviews in Allergy & Immunology

, Volume 34, Issue 1, pp 74–79 | Cite as

Rituximab: Beyond Simple B Cell Depletion

  • A. Kessel
  • I. Rosner
  • E. ToubiEmail author
Article

Abstract

Rituximab, a chimeric anti-CD20 monoclonal antibody, has a proven track record for over a decade in the treatment of lymphomas, where it has been used to eradicate malignant lymphocytes. In appreciation of the putative role of B cells, especially with respect to autoantibody production, in the pathogenesis of autoimmune diseases, successful trials of B-cell depletion therapy in RA, SLE, and other autoimmune diseases have been carried out. In these trials, clinical benefit has generally correlated with the extent and duration of B-cell depletion, but at times imperfectly, and autoantibody reduction only selectively. Additional mechanisms whereby rituximab may assert its clinical benefit in autoimmune diseases have been examined including a look at B-cell functions as T-cell modulator and antigen-presenting cell, T-regulatory cell behavior, NK cell activity, and macrophage activities in immune inflammation. The available data on rituximab’s action in autoimmune diseases is reviewed.

Keywords

Rituximab B-cell depletion Lymphomas 

References

  1. 1.
    Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R et al (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83:435–445PubMedGoogle Scholar
  2. 2.
    Jhonson PW, Glennie MJ (2001) Rituximab: mechanisms and applications. Br J Cancer 85:1619–1623CrossRefGoogle Scholar
  3. 3.
    Olszewski AJ, Grossbard ML (2004) Empowering targeted therapy: lessons from rituximab. Sci STKE 241:pe30CrossRefGoogle Scholar
  4. 4.
    Grillo-Lopez AJ (2000) Rituximab: an insider’s historical perspective. Semin Oncol 27(suppl):9–16PubMedGoogle Scholar
  5. 5.
    Shlomchik MJ, Madaio MP, Ni D, Trounslein M, Huszar D (1994) The role of B cells in lpr/lpr induced autoimmunity. J Exp Med 180:1295–306PubMedCrossRefGoogle Scholar
  6. 6.
    Lipsky PE (2001) Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat Immunol 2:764–766PubMedCrossRefGoogle Scholar
  7. 7.
    Youinou P, Lydyard PM, Mageed RA (2002) B cells underpin lupus immunopathology. Lupus 11:1–3PubMedCrossRefGoogle Scholar
  8. 8.
    Rivera A, Chen CC, Ron N, Dougherty JP, Ron Y (2001) Role of B cells as antigen presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations. Int Immunol 13:1583–1593PubMedCrossRefGoogle Scholar
  9. 9.
    Edwards JC, Cambridge G (2001) Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes. Rheumatology (Oxford) 40:205–211CrossRefGoogle Scholar
  10. 10.
    Weide R, Heymanns J, Pandorf A, Koppler H (2003) Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy. Lupus 12:779–782PubMedCrossRefGoogle Scholar
  11. 11.
    Ten Cate R, Smiers FJ, Bredius RG, Lankester AC, van Suijlekom-Smit LW, Huizinga TW, Egeler RM (2004) Anti-CD20 monoclonal antibody (rituximab) for refractory autoimmune thrombocytopenia in a girl with systemic lupus erythematosus. Rheumatology (Oxford) 43:244CrossRefGoogle Scholar
  12. 12.
    Stasi R, Stipa E, Del Poeta G, Amadori S, Newland AC, Provan D (2006) Long-term observation of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis treated with rituximab. Rheumatology (Oxford) 45:1432–1436CrossRefGoogle Scholar
  13. 13.
    Gottenberg JE, Guillevin L, Lambotte O, Combe B, Allanore Y, Cantagrel A, Larroche C et al (2005) Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis 64:913–920PubMedCrossRefGoogle Scholar
  14. 14.
    Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T (2004) Efficacy of B-cell targeted therapy with rituximab in patients with RA. N Eng J Med 350:2572–2581CrossRefGoogle Scholar
  15. 15.
    Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JC (2006) Reconstitution of peripheral blood B cells after depletion with rituximab in patients with RA. Arthritis Rheum 54:613–620PubMedCrossRefGoogle Scholar
  16. 16.
    Leandro MJ, Cambridge G, Edwards JC, Ehrenstein MR, Isenberg DA (2005) B-cell depletion in the treatment of patients with systemic lupus erythematosus: a longitudinal analysis of 24 patients. Rheumatology 44:1542–1545PubMedCrossRefGoogle Scholar
  17. 17.
    Sfikakis PP, Boletis JN, Lionaki S, Vigklis V, Fragiadaki KG, Iniotaki A, Moutsopoulos HM (2005) Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell co-stimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum 52:501–513PubMedCrossRefGoogle Scholar
  18. 18.
    Anolik JH, Barnard J, Cappione A, Pugh-Bernard AE, Felgar RE, Looney RJ, Sanz I (2004) Rituximab improves peripheral B cell abnormalities in human SLE. Arthritis Rheum 50:3580–3590PubMedCrossRefGoogle Scholar
  19. 19.
    Smith KG, Jones RB, Burns SM, Jayne DR (2006) Long-term comparison of rituximab treatment for refractory systemic lupus erythematosus and vasculitis: remission, relapse, and re-treatment. Arthritis Rheum 54:2970–2982PubMedCrossRefGoogle Scholar
  20. 20.
    Cambridge G, Leandro MJ, Edwards JC, Ehrenstein MR, Salden M, Bodman-Smith M, Webster AD (2003) Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum 48:2146–2154PubMedCrossRefGoogle Scholar
  21. 21.
    Sfikakis PP, Boletis JN, Tsokos GC (2005) Rituximab anti-B-cell therapy in systemic lupus erythematosus: pointing to the future. Curr Opin Rheumatol 17:550–557PubMedCrossRefGoogle Scholar
  22. 22.
    Thatayatikom A, White AJ (2006) Rituximab: a promising therapy in systemic lupus erythematosus. Autoimmunity Rev 5:18–24CrossRefGoogle Scholar
  23. 23.
    Cambridge G, Stohl W, Leandro MJ, Migone TS, Hilbert DM, Edwards JC (2006) Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment. Arthritis Rheum 54:723–732PubMedCrossRefGoogle Scholar
  24. 24.
    Toubi E, Kessel A, Slobodin G, Boulman N, Pavlotzky E, Zisman D, Rozenbaum M, Rosner I (2006) Macrophage function changes following rituximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis 66:818–820PubMedCrossRefGoogle Scholar
  25. 25.
    Tokunaga M, Fujii K, Saito K, Nakayamada S, Tsujimura S, Nawata M, Tanaka Y (2005) Down-regulation of CD40 and CD80 on B cells in patients with life-threatening systemic lupus erythematosus after successful with rituximab. Rheumatology 44:176–182PubMedCrossRefGoogle Scholar
  26. 26.
    Vigna-Perez M, Hernandez-Castro B, Paredes-Sapharopulos O, Portales-Perez D, Baranda L, Abud-Mendoz C, Gonzalez-Amaro R (2006) Clinical and immunological effects of rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res Ther 8:R83PubMedCrossRefGoogle Scholar
  27. 27.
    Vallerskog T, Gunnarsson I, Widhe M, Risselada A, Klareskog L, Van Vollenhoven R, Malmstrom V, Trollmo C (2007) Treatment with rituximab affects both the cellular and the humoral arms of the immune system in patients with SLE. Clin Immunol 122:62–74PubMedCrossRefGoogle Scholar
  28. 28.
    Golay J, Managanini M, Facchinetti V, gramigna R, Broady R, Borleri G, Rambaldi A, Introna M (2003) Rituximab-mediated antibody-dependent cellular cytotoxicity against neoplastic B cells is stimulated strongly by IL-2. Haematologica 88:1002–1012PubMedGoogle Scholar
  29. 29.
    Lefebvre ML, Krause SW, Salcedo M, Nardin A (2006) Ex vivo-activated human macrophages kill chronic lymphocytic leukemia cells in the presence of rituximab: mechanism of antibody-dependent cellular cytotoxicity and impact of human serum. J Immunother 29:388–397PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  1. 1.Division of Clinical Immunology and Allergy, Bnai Zion Medical Center, TechnionRappaport Faculty of MedicineHaifaIsrael
  2. 2.Rheumatology Unit, Bnai Zion Medical Center, TechnionRappaport Faculty of MedicineHaifaIsrael

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