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Blood, 1 June 2008, Vol. 111, No. 11, pp. 5334-5341. Prepublished online as a Blood First Edition Paper on February 21, 2008; DOI 10.1182/blood-2007-11-122713. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-11-122713v1 111/11/5334    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Saadoun, D. Articles by Cacoub, P. Search for Related Content PubMed PubMed Citation Articles by Saadoun, D. Articles by Cacoub, P. Related Collections Immunobiology Free Research Articles Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Restoration of peripheral immune homeostasis after rituximab in mixed cryoglobulinemia vasculitis David Saadoun*,1,2, Michelle Rosenzwajg*,1, Dan Landau1, Jean Charles Piette2, David Klatzmann,1, and Patrice Cacoub,1,2 1 Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Centre National de Recherche/Université Pierre et Marie Curie, Unité Médicale de Recherche 7087, Paris; and 2 Service de Médecine Interne, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France Rituximab, an anti-CD20 monoclonal antibody, has been used to treat autoimmune disorders such as mixed cryoglobulinemia (MC). However, its mechanisms of action as well as the effects on cellular immunity remain poorly defined. We investigated the changes of peripheral blood B- and T-cell subsets, the clonal VH1–69 cells, as well as the cytokine profile following rituximab therapy. The study involved 21 patients with hepatitis C–related MC who received rituximab, of whom 14 achieved a complete response. Compared with healthy and hepatitis C virus (HCV) controls, pretreatment abnormalities in MC patients included a decreased percentage of naive B cells (P < .05) and CD4+CD25+FoxP3+ regulatory T cells (P = .02) with an increase in memory B cells (P = .03) and plasmablasts (P < .05). These abnormalities were reverted at 12 months after rituximab. Clonal VH1–69+ B cells dramatically decreased following treatment (32% ± 6% versus 8% ± 2%, P = .01). Complete responders of rituximab exhibited an expansion of regulatory T cells (P < .01) accompanied with a decrease in CD8+ T-cell activation (P < .01) and decreased production of interleukin 12 (IL-12; P = .02) and interferon- (IFN-; P = .01). Our findings indicate that in patients with MC, response to B-cell depletion induced by rituximab effectively normalizes many of the disturbances in peripheral B- and T-lymphocyte homeostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Critiquing Cryos Morie Gertz Blood 2008 111: 5267. [Full Text] [PDF] This article has been cited by other articles: S. Andre, D. F. Tough, S. Lacroix-Desmazes, S. V. Kaveri, and J. Bayry Surveillance of Antigen-Presenting Cells by CD4+CD25+ Regulatory T Cells in Autoimmunity: Immunopathogenesis and Therapeutic Implications Am. J. Pathol., May 1, 2009; 174(5): 1575 - 1587. [Abstract] [Full Text] [PDF] Reversing Immunopathology with Rituximab in Cryoglobulinemia Patients Journal Watch Oncology and Hematology, June 17, 2008; 2008(617): 3 - 3. [Full Text]

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