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The Role of Rituximab in the Therapy of Mixed Cryoglobulinemia

  • Francesco Zaja
  • Stefano Volpetti
  • Stefano De Luca
  • Renato Fanin
Chapter

Abstract

The chimeric monoclonal antibody (IgG1/κ) rituximab (RTX) is directed against the CD20 antigen, expressed on the surface of normal (from pre-B to mature B lymphocytes) and malignant B lymphocytes. Since mixed cryoglobulinemia is sustained by a low-grade B lymphoproliferation exhibiting autoimmune features, there is a strong rationale for using RTX in the treatment of this disorder. Almost all clinical manifestations of mixed cryoglobulinemia may benefit from RTX treatment, and the antibody is generally well tolerated and safe. Caution should be exerted in patients with high cryoglobulin levels or hyperviscosity at baseline, because of possible flare syndrome. Although RTX can lead to an increase of HCV viremia, hepatitis re-activation is rarely observed. Prospective comparative trials are warranted in order to better evaluate the therapeutic impact of RTX and to define the best treatment approach.

Keywords

Mixed Cryoglobulinemia Rheumatoid Factor Level Hyperviscosity Syndrome Mixed Cryoglobulinemia Patient Mixed Cryoglobulins 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Ferri C (2008) Mixed cryoglobulinemia. Orphanet J Rare Dis 3:25PubMedCrossRefGoogle Scholar
  2. 2.
    Andreone P, Zignego AL, Cursaro C et al (1998) Prevalence of monoclonal gammopathies in patients with hepatitis C virus infection. Ann Intern Med 129:294–298PubMedCrossRefGoogle Scholar
  3. 3.
    Mangia A, Clemente R, Musto P et al (1996) Hepatitis C virus infection and monoclonal gammopathies not associated with cryoglobulinemia. Leukemia 10:1209–1213PubMedGoogle Scholar
  4. 4.
    Pozzato G, Mazzaro C, Santini G et al (1996) Hepatitis C virus and non-Hodgkin’s lymphomas. Leuk Lymphoma 22:53–60PubMedCrossRefGoogle Scholar
  5. 5.
    Gordon SC (1996) Extrahepatic manifestations of hepatitis C. Dig Dis 14:157–168PubMedCrossRefGoogle Scholar
  6. 6.
    Charles ED, Dustin LB (2009) Hepatitis C virus-induced cryoglobulinemia. Kidney Int 76:818–824PubMedCrossRefGoogle Scholar
  7. 7.
    Sène D, Limal N, Ghillani-Dalbin P et al (2007) Hepatitis C virus-associated B-cell proliferation–the role of serum B lymphocyte stimulator (BLyS/BAFF). Rheumatology (Oxford) 46:65–69CrossRefGoogle Scholar
  8. 8.
    Reff ME, Carner K, Chambers KS et al (1995) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83:435–445Google Scholar
  9. 9.
    Golay J, Zaffaroni L, Vaccari T et al (2000) Biologic response of B-lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood 95:3900–3908PubMedGoogle Scholar
  10. 10.
    Shan D, Ledbetter JA, Press OW (2000) Signaling events involved in anti-CD20 induced apoptosis of malignant humam B-cells. Cancer Immunol Immunother 48:673–683PubMedCrossRefGoogle Scholar
  11. 11.
    Hofmeister JK, Cooney D, Coggeshall KM (2000) Clustered CD20-induced apoptosis: Src-family kinase, the proximal regulator of tyrosine phosporylation calcium influx and ­caspase 3-dependent apoptosis. Blood Cells Mol Dis 26:133–143PubMedCrossRefGoogle Scholar
  12. 12.
    Maloney DG, Grillo-Lopez AJ, White CA et al (1997) IDEC-C2B8 (rituximab) anti CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood 90:2188–2195PubMedGoogle Scholar
  13. 13.
    Zaja F, De Vita S, Mazzaro C et al (2003) Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood 101:3827–3834PubMedCrossRefGoogle Scholar
  14. 14.
    Zaja F, Russo D, Fuga G et al (1999) Rituximab for the treatment of type II mixed cryoglobulinemia. Haematologica 84:1157–1158PubMedGoogle Scholar
  15. 15.
    De Vita S, Zaja F, Sacco S et al (2002) Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis: evidence for a pathogenetic role of B cells. Arthritis Rheum 46:2029–2033PubMedCrossRefGoogle Scholar
  16. 16.
    Zaja F, De Vita S, Russo D et al (2002) Rituximab for the treatment of type II mixed cryoglobulinemia. Arthritis Rheum 46:2252–2254PubMedCrossRefGoogle Scholar
  17. 17.
    Sansonno D, De Re V, Lauletta G et al (2003) Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20. Blood 101:3818–3826PubMedCrossRefGoogle Scholar
  18. 18.
    Roccatello D, Baldovino S, Rossi D et al (2004) Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobulinaemic glomerulonephritis. Nephrol Dial Transplant 19:3054–3061PubMedCrossRefGoogle Scholar
  19. 19.
    da Silva Fucuta Pereira P, Lemos LB, de Oliveira Uehara SN et al (2010) Long-term efficacy of rituximab in hepatitis C virus-associated cryoglobulinemia. Rheumatol Int 30:1515–1518PubMedCrossRefGoogle Scholar
  20. 20.
    Arzoo K, Sadeghi S, Liebman HA (2002) Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). Ann Rheum Dis 61:922–924PubMedCrossRefGoogle Scholar
  21. 21.
    Lamprecht P, Lerin-Lozano C, Merz H et al (2003) Rituximab induces remission in refractory HCV associated cryoglobulinaemic vasculitis. Ann Rheum Dis 62:1230–1233PubMedCrossRefGoogle Scholar
  22. 22.
    Koukoulaki M, Abeygunasekara SC, Smith KG et al (2005) Remission of refractory hepatitis C-negative cryoglobulinaemic vasculitis after rituximab and infliximab. Nephrol Dial Transplant 20:213–216PubMedCrossRefGoogle Scholar
  23. 23.
    Ghobrial IM, Uslan DZ, Call TG et al (2004) Initial increase in the cryoglobulin level after rituximab therapy for type II cryoglobulinemia secondary to Waldenström macroglobulinemia does not indicate failure of response. Am J Hematol 77:329–330PubMedCrossRefGoogle Scholar
  24. 24.
    Ghijsels E, Lerut E, Vanrenterghem Y et al (2004) Anti-CD20 monoclonal antibody (rituximab) treatment for hepatitis C-negative therapy-resistant essential mixed cryoglobulinemia with renal and cardiac failure. Am J Kidney Dis 43:34–38CrossRefGoogle Scholar
  25. 25.
    Cohen H, Green S, Jones S et al (2007) Lack of efficacy of Rituximab in a patient with essential mixed cryoglobulinaemia. Rheumatology (Oxford) 46:366–367CrossRefGoogle Scholar
  26. 26.
    Visentini M, Granata M, Veneziano ML et al (2007) Efficacy of low-dose rituximab for mixed cryoglobulinemia. Clin Immunol 125:30–33PubMedCrossRefGoogle Scholar
  27. 27.
    Saadoun D, Resche-Rigon M, Sene D et al (2008) Rituximab combined with Peg-interferon-ribavirin in refractory hepatitis C virus-associated cryoglobulinaemia vasculitis. Ann Rheum Dis 67:1431–1436PubMedCrossRefGoogle Scholar
  28. 28.
    Tallarita T, Gagliano M, Corona D et al (2009) Successful combination of Rituximab and plasma exchange in the treatment of cryoglobulinemic vasculitis with skin ulcers: a case report. Cases J 2:7859PubMedCrossRefGoogle Scholar
  29. 29.
    Quartuccio L, Soardo G, Romano G et al (2006) Rituximab treatment for glomerulonephritis in HCV-associated mixed cryoglobulinaemia: efficacy and safety in the absence of steroids. Rheumatology (Oxford) 45:842–846CrossRefGoogle Scholar
  30. 30.
    Basse G, Ribes D, Kamar N et al (2006) Rituximab therapy for mixed cryoglobulinemia in seven renal transplant patients. Transplant Proc 38:2308–2310PubMedCrossRefGoogle Scholar
  31. 31.
    Cavallo R, Roccatello D, Menegatti E et al (2009) Rituximab in cryoglobulinemic peripheral neuropathy. J Neurol 256:1076–1082PubMedCrossRefGoogle Scholar
  32. 32.
    Monti G, Galli M, Invernizzi F et al (1995) Cryoglobulinaemias: a multi-centre study of the early clinical and laboratory ­manifestations of primary and secondary disease. GISC. Italian Group for the Study of Cryoglobulinaemias. QJM 88:115–126PubMedGoogle Scholar
  33. 33.
    Ghobrial IM, Gertz MA, Fonseca R (2003) Waldenstrom macroglobulinaemia. Lancet Oncol 4:679–685PubMedCrossRefGoogle Scholar
  34. 34.
    Sène D, Ghillani-Dalbin P, Amoura Z et al (2009) Rituximab may form a complex with IgMkappa mixed cryoglobulin and induce severe systemic reactions in patients with hepatitis C virus-induced vasculitis. Arthritis Rheum 60:3848–3855PubMedCrossRefGoogle Scholar
  35. 35.
    Roccatello D, Baldovino S, Rossi D et al (2008) Rituximab as a therapeutic tool in severe mixed cryoglobulinemia. Clin Rev Allergy Immunol 34:111–117PubMedCrossRefGoogle Scholar
  36. 36.
    Sansonno D, Tucci FA, Montrone M et al (2007) B-cell depletion in the treatment of mixed cryoglobulinemia. Dig Liver Dis 39(Suppl 1):S116–S121PubMedCrossRefGoogle Scholar
  37. 37.
    Quartuccio L, Salvin S, Fabris M et al (2008) Disapp­earance of bone marrow B cell clonal expansion in patients with type II hepatitis C virus-related cryoglobulinemic ­glomerulonephritis after clinical efficient rituximab therapy. Ann Rheum Dis 67:1494–1495PubMedCrossRefGoogle Scholar
  38. 38.
    Gasparotto D, De Vita S, De Re V et al (2003) Extrasalivary lymphoma development in Sjögren’s syndrome: clonal evolution from parotid gland lymphoproliferation and role of local triggering. Arthritis Rheum 48:3181–3186PubMedCrossRefGoogle Scholar
  39. 39.
    De Re V, De Vita S, Marzotto A et al (2000) Sequence analysis of the immunoglobulin antigen receptor of hepatitis C virus-associated non-Hodgkin lymphomas suggests that the malignant cells are derived from the rheumatoid factor-­producing cells that occur mainly in type II cryoglobulinemia. Blood 96:3578–3584PubMedGoogle Scholar
  40. 40.
    Roulland S, Suarez F, Hermine O, Nadel B (2008) Patho­physiological aspects of memory B-cell development. Trends Immunol 29:25–33PubMedCrossRefGoogle Scholar
  41. 41.
    Lake-Bakaar G, Dustin L, McKeating J et al (2007) Hepatitis C virus and alanine aminotransferase kinetics following B-lymphocyte depletion with rituximab: evidence for a significant role of humoral immunity in the control of viremia in chronic HCV liver disease. Blood 109:845–846PubMedCrossRefGoogle Scholar
  42. 42.
    Catuogno M, Rezai S, Priori R et al (2005) Serum sickness associated with rituximab in a patient with hepatitis C virus-related mixed cryoglobulinaemia. Rheumatology (Oxford) 44:406CrossRefGoogle Scholar
  43. 43.
    Meersseman W, Lagrou K, Sciot R et al (2007) Rapidly fatal Acanthamoeba encephalitis and treatment of cryoglobulinemia. Emerg Infect Dis 13:469–471PubMedCrossRefGoogle Scholar
  44. 44.
    Basse G, Ribes D, Kamar N et al (2005) Rituximab therapy for de novo mixed cryoglobulinemia in renal transplant patients. Transplantation 80:1560–1564PubMedCrossRefGoogle Scholar
  45. 45.
    Ruch J, McMahon B, Ramsey G et al (2009) Catastrophic multiple organ ischemia due to an anti-Pr cold agglutinin developing in a patient with mixed cryoglobulinemia after treatment with rituximab. Am J Hematol 84(2):120–122PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Francesco Zaja
    • 1
  • Stefano Volpetti
    • 1
  • Stefano De Luca
    • 1
  • Renato Fanin
    • 1
  1. 1.Clinica Ematologica, DISMAzienda Ospedaliero Universitaria S. Maria MisericordiaUdineItaly

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