The Journal of Allergy and Clinical Immunology
Volume 121, Issue 1 , Pages 122-128 , January 2008

Anti-CD20 (rituximab) treatment improves atopic eczema

  • Dagmar Simon, MD

      Affiliations

    • Department of Dermatology, Inselspital, University of Bern, Bern, Switzerland
  • ,
  • Susanne Hösli, MD

      Affiliations

    • Department of Pharmacology, University of Bern, Bern, Switzerland
  • ,
  • Ganna Kostylina, PhD

      Affiliations

    • Department of Pharmacology, University of Bern, Bern, Switzerland
  • ,
  • Nikhil Yawalkar, MD

      Affiliations

    • Department of Dermatology, Inselspital, University of Bern, Bern, Switzerland
  • ,
  • Hans-Uwe Simon, MD, PhD

      Affiliations

    • Department of Pharmacology, University of Bern, Bern, Switzerland
    • Corresponding Author InformationReprint requests: Hans-Uwe Simon, MD, PhD, Department of Pharmacology, University of Bern, Friedbühlstrasse 49, CH-3010 Bern, Switzerland.

Received 2 October 2007 ,Revised 14 November 2007 ,Accepted 14 November 2007.

References 

  1. Novak N, Bieber T, Leung DYM. Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol. 2003;112:S128–S139
  2. Akdis CA, Akdis M, Simon D, Dibbert B, Weber M, Gratzl S, et al. T cells and T cell-derived cytokines as pathogenic factors in the non-allergic form of atopic dermatitis. J Invest Dermatol. 1999;113:628–634
  3. Lugovic L, Lipozenocic J, Jakic-Razumovic J. Atopic dermatitis: immunophenotyping of inflammatory cells in skin lesions. Int J Dermatol. 2001;40:489–494
  4. Simon D, Vassina E, Yousefi S, Kozlowski E, Braathen L, Simon HU. Reduced dermal infiltration of cytokine-expressing cells in atopic dermatitis following short-term topical tacrolimus treatment. J Allergy Clin Immunol. 2004;114:887–895
  5. Simon D, Vassina E, Yousefi S, Braathen LR, Simon HU. Inflammatory cell numbers and cytokine expression in atopic dermatitis after topical pimecrolimus treatment. Allergy. 2005;60:944–951
  6. Schmid-Grendelmeier P, Simon D, Simon HU, Akdis CA, Wüthrich B. Epidemiology, clinical features, and immunology of the intrinsic (non-IgE-mediated) type of atopic dermatitis (constitutional dermatitis). Allergy. 2001;56:841–849
  7. Bruynzeel-Koomen C, van Wichen DF, Toonstra J, Berrens L, Bruynzeel PL. The presence of IgE molecules on epidermal Langerhans cells in patients with atopic dermatitis. Arch Dermatol Res. 1986;278:199–205
  8. Grillo-Lopez AJ, White CA, Varns C, Shen D, Wei A, McClure A, et al. Overview of the clinical development of rituximab: first monoclonal antibody for the treatment of lymphoma. Semin Oncol. 1999;26:66–73
  9. Jezirehi AR, Bonavida B. Cellular and molecular signal transduction pathways modulated by rituximab (rituxan, anti-CD20 mAb) in non-Hodgkin's lymphoma: implications in chemosensitization and therapeutic intervention. Oncogene. 2005;24:2121–2143
  10. Cancro MP, Allman DM, Hayes CE, Lentz VM, Fields RG, Sah AP, et al. B cell maturation and the selection at the marrow-periphery interface. Immunol Res. 1998;17:3–11
  11. De Vita S, Zaja F, Sacco S, De Candia A, Fanin R, Ferraccioli G. Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis: evidence for a pathogenic role of B cells. Arthritis Rheum. 2002;46:2029–2033
  12. Leandro MJ, Edwards JCW, Cambridge G. Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion. Ann Rheum Dis. 2002;61:883–888
  13. Edwards JCW, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350:2572–2581
  14. Leandro MJ, Edwards JC, Cambridge G, Ehrenstein MR, Isenberg DA. An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis Rheum. 2002;46:2673–2677
  15. Looney RJ, Anolik JH, Campbell D, Felgar RE, Young F, Arend LJ, et al. B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum. 2004;50:2580–2589
  16. Dupuy A, Viguier M, Bedane C, Cordoliani F, Blaise S, Aucouturier F, et al. Treatment of refractory pemphigus vulgaris with rituximab (anti-CD20 monoclonal antibody). Arch Dermatol. 2004;140:91–96
  17. Morrison LH. Therapy of refractory pemphigus vulgaris with monoclonal anti-CD20 antibody (rituximab). J Am Acad Dermatol. 2004;51:817–819
  18. Arin MJ, Engert A, Krieg T, Hunzelmann N. Anti-CD20 monoclonal antibody (rituximab) in the treatment of pemphigus. Br J Dermatol. 2005;153:620–625
  19. Ahmed AR, Spigelman Z, Cavacini LA, Rosner MR. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. 2006;355:1772–1779
  20. Joly P, D'Incan M, Musette P. Rituximab for pemphigus vulgaris. N Engl J Med. 2007;356:521–522
  21. Silverman GJ, Weisman S. Rituximab therapy and autoimmune disorders. Arthritis Rheum. 2003;48:1484–1492
  22. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venerol (Stockh). 1980;92:S44–S47
  23. Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity index (EASI): assessment of reliability an atopic dermatitis. Exp Dermatol. 2001;10:11–18
  24. Simon HU, Plötz SG, Dummer R, Blaser K. Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med. 1999;341:1112–1120
  25. Simon HU, Seelbach H, Ehmann R, Schmitz M. Clinical and immunological effects of low dose IFN-α treatment in patients with corticosteroid-resistant asthma. Allergy. 2003;58:1250–1255
  26. Simon D, Braathen LR, Simon HU. Increased lipopolysaccharide-induced TNF-α, IFN-γ, and IL-10 production in atopic dermatitis. Br J Dermatol. 2007;157:583–586
  27. Simon D, Borelli S, Braathen LR, Simon HU. Peripheral blood mononuclear cells from extrinsic and intrinsic atopic dermatitis patients demonstrate increased capacity of generating interleukin-13 but differ in their potential of synthesising interferon-γ. Allergy. 2002;57:431–435
  28. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;18:3–7
  29. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (Duluth). 2001;25:402–408
  30. Lipsky PE. Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nature Immunol. 2001;2:764–766
  31. Silverman GJ. Anti-CD20 therapy and autoimmune disease: therapeutic opportunities and evolving insights. Front Biosci. 2007;12:2194–2206
  32. Stockinger B, Zal T, Zal A, Gray D. B cells solicit their own help from T cells. J Exp Med. 1996;183:891–899
  33. Macaulay AE, DeKruyff RH, Goodnow CC, Umetsu DT. Antigen-specific B cells preferentially induce CD4+ T cells to produce IL-4. J Immunol. 1997;158:4171–4179
  34. Clark R, Kupper T. Old meets new: the interaction between innate and adaptive immunity. J Invest Dermatol. 2005;125:629–637
  35. Jirapongsananuruk O, Hofer MF, Trumble AE, Norris DA, Leung DY. Enhanced expression of B7.2 (CD86) in patients with atopic dermatitis: a potential role in the modulation of IgE synthesis. J Immunol. 1998;160:4622–4627
  36. Sfikakis PP, Boletis JN, Lionaki S, Vigklis V, Fragiadaki KG, Iniotaki A, et al. Remission of proliferative lupus nephritis following B cells depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum. 2005;52:501–513
  37. Takemura S, Klimiuk PA, Braun A, Goronzy JJ, Weyand CM. T cell activation in rheumatoid synovium is B cell dependent. J Immunol. 2001;167:4710–4718
  38. Lin L, Nonoyama A, Oshiba A, Kabasawa Y, Mizutani S. TARC and MDC are produced by CD40 activated human B cells and are elevated in the sera of infantile atopic dermatitis patients. J Med Dent Sci. 2003;50:27–33
  39. Frezzolini A, Paradisi M, Zaffiro A, Provini A, Cadoni S, Ruffelli M, et al. Circulating interleukin 16 (IL-16) in children with atopic eczema/dermatitis syndrome (AEDS): a novel serological marker of disease activity. Allergy. 2002;57:815–820
  40. Masuda K, Katoh N, Okuda F, Kishimoto S. Increased levels of serum interleukin 16 in adult type atopic dermatitis. Acta Derm Venereol. 2003;83:249–253
  41. Kaser A, Dunzendorfer S, Offner FA, Ludwiczek O, Enrich B, Koch RO, et al. B lymphocyte-derived IL-16 attracts dendritic cells and Th cells. J Immunol. 2000;165:2474–2480
  42. Harada H, Kawano MM, Huang N, Harada Y, Iwato K, Tanabe O, et al. Phenotypic difference of normal plasma cells from mature myeloma cells. Blood. 1993;81:2658–2663
  43. Manz RA, Thiel A, Radbruch A. Lifetime of plasma cells in the bone marrow. Nature. 1997;388:133–134
  44. Cambridge G, Leandro MJ, Edwards JC, Ehrenstein MR, Salden M, Bodman-Smith M, et al. Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum. 2003;48:2146–2154
  45. Vallerskog T, Gunnarsson I, Widhe M, Risselada A, Klareskog L, Van Vollenhoven R, et al. Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin Immunol. 2007;122:62–74
  46. Eisenberg R, Looney RJ. The therapeutic potential of anti-CD20. What do B cells do?. Clin Immunol. 2005;117:207–213
  47. Cooper HL, Healy E, Theaker JM, Friedmann PS. Treatment of resistant pemphigus vulgaris with an anti-CD20 monoclonal antibody (rituximab). Clin Exp Dermatol. 2003;28:366–368
  48. Sfikakis PP, Boletis JN, Tsokos GC. Rituximab anti-B-cell therapy in systemic lupus erythematosus: pointing to the future. Curr Opin Rheumatol. 2005;17:550–557
  49. Levesque MC, St. Clair EW. B cell–directed therapies for autoimmune disease and correlates of disease response and relapse. J Allergy Clin Immunol. 2008;121:13–21

 Supported by grants from the Swiss National Science Foundation (310000-107526) and Roche Pharma AG, Reinach.

 Disclosure of potential conflict of interest: The authors have declared that they have received research support from Roche Pharma AG.

PII: S0091-6749(07)02253-1

doi: 10.1016/j.jaci.2007.11.016

The Journal of Allergy and Clinical Immunology
Volume 121, Issue 1 , Pages 122-128 , January 2008