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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2784-2785. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Semple, J. W. Search for Related Content PubMed Articles by Semple, J. W. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS Comment on Stasi et al, page 2924 Rituximab disciplines T cells, spares platelets John W. Semple TORONTO PLATELET IMMUNOBIOLOGY GROUP AT SAINT MICHAEL'S HOSPITAL Just when we're comfortable thinking that Rituximab's efficacy in idiopathic thrombocytopenic purpura (ITP) is due directly to B-cell depletion, along comes a paper that challenges the notion. It appears that B-cell depletion really affects abnormal T-cell subsets and only these changes correlate with increased platelet counts; this may change the game of how we view therapeutic design in ITP. Rituximab (Rituxan), a monoclonal anti-CD20 antibody, is an efficacious therapy in patients with non-Hodgkin lymphoma. There has also been a great deal of interest in its beneficial effects in patients with several autoimmune disorders, including idiopathic thrombocytopenic purpura (ITP). A systematic review of several noncontrolled trials has shown that the use of this monoclonal antibody produces platelet responses in approximately 62% of patients with chronic ITP.1 The mechanism of action of rituximab in ITP is assumed to be due to selective depletion of CD20+ B cells, which affects autoantibody development.2 Although the pathogenesis of ITP is autoantibody-mediated, IgG autoantibodies are driven by T-cell–dependent mechanisms and many reports have described several consistent T-cell abnormalities in ITP.3 The efficacy of a B-cell–depleting therapy, despite the presence of autoreactive T cells, led Stasi and colleagues in this issue to demonstrate that the therapeutic efficacy of rituximab is actually due to normalizing abnormal autoreactive T-cell responses in patients with ITP. The authors studied 30 adult patients with chronic ITP that were treated with the standard rituximab dose of 375 mg/m2 weekly for 4 weeks, and employed a variety of sophisticated techniques to analyze several T-cell parameters prior to treatment and at 3, 6, and 12 months after treatment. The results were correlated with the patients' responder status. What they found was not only convincing, but quite astonishing. The pretreatment T-cell abnormalities, including elevated Th1/Th2 (and Tc1/Tc2) cytokine ratios, elevated CD4+ T-cell–associated Bcl-2/Bax mRNA levels, and oligoclonal T-cell expansion, were completely reversed by 3 months after treatment. This was observed only in those patients who responded to rituximab therapy; these normalization changes persisted for as long as 6 to 12 months after therapy. These results suggest the intriguing hypothesis that only when T-cell subsets can be modulated is rituximab therapy effective. The reasons for these results are not clear, but may relate to how B-cell populations can be important in maintaining T-cell activation patterns by interactions such as CD40/CD40L ligation. The results are also consistent with the recently reported efficacy of rituximab in patients with refractory chronic graft-versus-host disease, which is known to be a T-cell–mediated disorder.4 Significantly decreasing the total mass of CD20+ B cells by rituximab therapy in ITP may cause a collapse of autoreactive T-cell stimulation and normalization of the T-cell repertoire even as the B cells begin to return months after the therapy. Clearly, more research is warranted to further understand this most interesting phenomenon. This important work truly lends credence to the notion that attacking T cells in ITP, even if via the slaughter of B cells, is perhaps the real way to design successful therapies for this disorder. Footnotes Conflict-of-interest disclosure: The author declares no competing financial interests. REFERENCES Arnold DM, Dentali F, Crowther MA, et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med 2007; 146:25–33.[Abstract/Free Full Text] Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 2001; 98:952–957.[Abstract/Free Full Text] Coopamah M, Garvey MB, Freedman J, Semple JW. Cellular immune mechanisms in autoimmune thrombocytopenic purpura: an update. Transfusion Med Rev 2003; 17:69–80.[CrossRef][Medline] [Order article via Infotrieve] Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D. Rituximab for steroid-refractory chronic graft-vs.-host disease. Blood 2006; 108:756–762.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Response to B-cell–depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura Roberto Stasi, Giovanni Del Poeta, Elisa Stipa, Maria Laura Evangelista, Margherita M. Trawinska, Nichola Cooper, and Sergio Amadori Blood 2007 110: 2924-2930. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Semple, J. W. Search for Related Content PubMed Articles by Semple, J. W. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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