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

Show simple item record Abrams, Judith R. en_US Lebwohl. Mark G. en_US Guzzo, Cynthia A. en_US Jegasothy. Brian V. en_US Goldfarb, Michael T. en_US Goffe, Bernard S. en_US Menter, Alan en_US Lowe, Nicholas J. en_US Krueger, Gerald en_US Brown, Michael J. en_US Weiner, Russell S. en_US Birkhofer, Martin J. en_US Warner, Garvin L. en_US Berry, Karen K. en_US Linsley, Peter S. en_US Krueger, James G. en_US Ochs, Hans D. en_US Kelley, Susan L. en_US Kang, Sewon en_US 2009-12-15T21:09:47Z 2009-12-15T21:09:47Z 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 en_US
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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