Efalizumab (anti-CD11a)-induced increase in peripheral blood leukocytes in psoriasis patients is preferentially mediated by altered trafficking of memory CD8+ T cells into lesional skin.
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| Abstract |
Therapeutic administration of efalizumab, a humanized antibody to CD11a, induces a marked but reversible increase of peripheral lymphocytes in psoriasis patients. In this study, 13 patients were treated with 12 weekly subcutaneous doses (2 mg/kg/week) of efalizumab, and all 13 patients had increases in leukocyte counts. This increased white blood cell count was mainly due to a 3- to 4-fold increase in the number of circulating CD3(+) lymphocytes during active treatment. Both naive and memory populations of CD4(+) and CD8(+) lymphocytes in the peripheral blood increased, with the largest increase observed in memory CD8(+) T cells. This CD8(+) memory T cell subset is a prominent T cell population found in psoriatic skin. An increase in Type 1 (IFN-gamma producing) T cells was also observed during treatment. Both components of LFA-1, CD11a and CD18, were downregulated during treatment, and surprisingly the integrins CD11b and beta 7 were similarly reduced. We conclude that efalizumab most likely blocks cutaneous entry of memory CD8(+) T cells, a highly disease-relevant cell population. The relatively smaller increase in naive peripheral blood T cells could be attributed to reduced trafficking of naive T cells.
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| Authors | Yulia Vugmeyster, Toyoko Kikuchi, Michelle A Lowes, Francesca Chamian, Mark Kagen, Patricia Gilleaudeau, Edmund Lee, Kathy Howell, Sarah Bodary, Wolfgang Dummer, James G Krueger |
| Journal | Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 113 Issue 1 Pg. 38-46 (Oct 2004) ISSN: 1521-6616 [Print] United States |
| PMID | 15380528 (Publication Type: Journal Article) |
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