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CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris

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dc.contributor.author Abrams, Judith R. en_US
dc.contributor.author Lebwohl. Mark G. en_US
dc.contributor.author Guzzo, Cynthia A. en_US
dc.contributor.author Jegasothy. Brian V. en_US
dc.contributor.author Goldfarb, Michael T. en_US
dc.contributor.author Goffe, Bernard S. en_US
dc.contributor.author Menter, Alan en_US
dc.contributor.author Lowe, Nicholas J. en_US
dc.contributor.author Krueger, Gerald en_US
dc.contributor.author Brown, Michael J. en_US
dc.contributor.author Weiner, Russell S. en_US
dc.contributor.author Birkhofer, Martin J. en_US
dc.contributor.author Warner, Garvin L. en_US
dc.contributor.author Berry, Karen K. en_US
dc.contributor.author Linsley, Peter S. en_US
dc.contributor.author Krueger, James G. en_US
dc.contributor.author Ochs, Hans D. en_US
dc.contributor.author Kelley, Susan L. en_US
dc.contributor.author Kang, Sewon en_US
dc.date.accessioned 2009-12-15T21:09:47Z
dc.date.available 2009-12-15T21:09:47Z
dc.date.issued 1999 en_US
dc.identifier.citation Abrams JR, Lebwohl MG, Guzzo CA, et al. CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest. 1999;103(9):1243-1252. en_US
dc.identifier.other 10.1172/JCI5857 en_US
dc.identifier.uri http://www.jci.org/articles/view/5857 en_US
dc.identifier.uri http://hdl.handle.net/1773/15538
dc.description.abstract Engagement of the B7 family of molecules on antigen-presenting cells with their T cell–associated ligands, CD28 and CD152 (cytotoxic T lymphocyte–associated antigen-4 [CTLA-4]), provides a pivotal costimulatory signal in T-cell activation. We investigated the role of the CD28/CD152 pathway in psoriasis in a 26-week, phase I, open-label dose-escalation study. The importance of this pathway in the generation of humoral immune responses to T cell–dependent neoantigens, bacteriophage φX174 and keyhole limpet hemocyanin, was also evaluated. Forty-three patients with stable psoriasis vulgaris received 4 infusions of the soluble chimeric protein CTLA4Ig (BMS-188667). Forty-six percent of all study patients achieved a 50% or greater sustained improvement in clinical disease activity, with progressively greater effects observed in the highest-dosing cohorts. Improvement in these patients was associated with quantitative reduction in epidermal hyperplasia, which correlated with quantitative reduction in skin-infiltrating T cells. No markedly increased rate of intralesional T-cell apoptosis was identified, suggesting that the decreased number of lesional T cells was probably likely attributable to an inhibition of T-cell proliferation, T-cell recruitment, and/or apoptosis of antigen-specific T cells at extralesional sites. Altered antibody responses to T cell–dependent neoantigens were observed, but immunologic tolerance to these antigens was not demonstrated. This study illustrates the importance of the CD28/CD152 pathway in the pathogenesis of psoriasis and suggests a potential therapeutic use for this novel immunomodulatory approach in an array of T cell–mediated diseases. en_US
dc.language.iso en_US en_US
dc.title CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris en_US
dc.type Article en_US


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