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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1229-1236. Prepublished online as a Blood First Edition Paper on October 9, 2003; DOI 10.1182/blood-2003-06-2167. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-2167v1 103/4/1229    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 Kuwana, M. Articles by Ikeda, Y. Search for Related Content PubMed PubMed Citation Articles by Kuwana, M. Articles by Ikeda, Y. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thrombocytopenic purpura Masataka Kuwana, Shosaku Nomura, Kingo Fujimura, Toshiro Nagasawa, Yoshitomo Muto, Yoshiyuki Kurata, Shigeru Tanaka, and Yasuo Ikeda From the Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan; the Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; the First Department of Internal Medicine, Kansai Medical University, Osaka, Japan; the Department of Hematology and Oncology, Division of Pharmacotherapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan; the Division of Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan; the Department of Hematology, Toranomon Hospital, Tokyo, Japan; the Department of Blood Transfusion, Osaka University Hospital, Osaka, Japan; and Eisai Company Ltd, Tokyo, Japan. Blockade of the CD40/CD154 signal is a potential immunomodulatory strategy for T-cell–mediated diseases. As a part of a phase 1, multicenter, dose-escalating trial of humanized monoclonal antibody to CD154 (IDEC-131/E6040) in patients with refractory immune thrombocytopenic purpura (ITP), the autoimmune response to glycoprotein IIb/IIIa (GPIIb/IIIa) was evaluated at successive time points. Five patients each were given a single infusion of 1, 2, 5, or 10 mg/kg IDEC-131/E6040 and followed for 3 months. All adverse events were mild, and there were no severe infections or thromboembolic events. No increase in platelet count was observed in patients treated at 1, 2, or 5 mg/kg, but an increase was observed in 3 patients treated at 10 mg/kg. In only the patients treated at 5 or 10 mg/kg, the frequency of B cells producing anti-GPIIb/IIIa antibodies, GPIIb/IIIa-induced T-cell proliferation, and anti-GPIIb/IIIa antibody production by antigen-dependent T–B-cell collaboration were all suppressed in parallel after the treatment, with a slow return to baseline. In contrast, T-cell response to an irrelevant antigen was not affected. These findings suggest that CD40/CD154 blockade therapy is potentially effective for refractory ITP, through selective suppression of autoreactive T and B cells to platelet antigens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Anti-CD40L: biology and therapy in ITP Joseph Schwartz and James B. Bussel Blood 2004 103: 1178-1179. [Full Text] [PDF] This article has been cited by other articles: S Danese, F Scaldaferri, S Vetrano, T Stefanelli, C Graziani, A Repici, R Ricci, G Straface, A Sgambato, A Malesci, et al. Critical role of the CD40 CD40-ligand pathway in regulating mucosal inflammation-driven angiogenesis in inflammatory bowel disease Gut, September 1, 2007; 56(9): 1248 - 1256. [Abstract] [Full Text] [PDF] H. Sukati, H. G. Watson, S. J. Urbaniak, and R. N. Barker Mapping helper T-cell epitopes on platelet membrane glycoprotein IIIa in chronic autoimmune thrombocytopenic purpura Blood, May 15, 2007; 109(10): 4528 - 4538. [Abstract] [Full Text] [PDF] M. Nakamura, Y. Tanaka, T. Satoh, M. Kawai, M. Hirakata, J. Kaburaki, Y. Kawakami, Y. Ikeda, and M. Kuwana Autoantibody to CD40 ligand in systemic lupus erythematosus: association with thrombocytopenia but not thromboembolism Rheumatology, February 1, 2006; 45(2): 150 - 156. [Abstract] [Full Text] [PDF] N. Sevier and M. Houston Chronic Refractory ITP in Children: Beyond Splenectomy Journal of Pediatric Oncology Nursing, May 1, 2005; 22(3): 145 - 151. [Abstract] [PDF]

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