Efalizumab therapy for atopic dermatitis causes marked increases in circulating effector memory CD4+ T cells that express cutaneous lymphocyte antigen.

Abstract

Efalizumab is an mAb directed against CD11a, a molecule involved in T-cell activation and extravasation from blood into tissue. Ten patients with severe atopic dermatitis were treated with efalizumab for 84 days, and peripheral blood mononuclear cells were analyzed for expression of activation and adhesion markers. Efalizumab treatment led to decreases in CD11a mean fluorescence intensity (MFI) on naive, central memory, and effector memory CD4+ and CD8+ T cell subsets. MFI for CD18 was decreased in both CD4+ and CD8+ T cells. Percentages of cells positive for cutaneous lymphocyte antigen (CLA) were increased fourfold in all CD4+ and CD8+ T cell subsets. Increases in the percentages of CD4+ and CD8+ T cells expressing beta7 and CD49d were also observed. No significant changes were observed in the percentages of CD4+ and CD8+ T cells that produced either IFN-gamma or IL-4. In summary, efalizumab treatment resulted in (i) decreases in CD11a and CD18 expression in all circulating T-cell subsets and (ii) increases in the percentages of blood T cells expressing tissue homing markers (CLA, beta7, CD49d). These data suggest that blockade of T-cell extravasation into tissue is the major pathway by which efalizumab leads to improvement in cutaneous inflammation.

• Authors: Erin G Harper, Eric L Simpson, Rodd H Takiguchi, Miranda D Boyd, Stephen E Kurtz, Antony C Bakke, Andrew Blauvelt
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 128 Issue 5 Pg. 1173-81 (May 2008) ISSN: 1523-1747 [Electronic] United States
• PMID: 18007580 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antigens, Differentiation, T-Lymphocyte
• Antigens, Neoplasm
• CD11a Antigen
• CD18 Antigens
• CD44 protein, human
• CTAGE1 protein, human
• Hyaluronan Receptors
• Integrin beta Chains
• Membrane Glycoproteins
• integrin beta7
• Integrin alpha4
• Interferon-gamma
• efalizumab

Topics

• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Antigens, Differentiation, T-Lymphocyte
• Antigens, Neoplasm (metabolism)
• CD11a Antigen (immunology, metabolism)
• CD18 Antigens (metabolism)
• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes (drug effects, immunology, metabolism)
• CD8-Positive T-Lymphocytes (drug effects, immunology, metabolism)
• Dermatitis, Atopic (drug therapy, immunology)
• Humans
• Hyaluronan Receptors (metabolism)
• Immunologic Memory (drug effects)
• Integrin alpha4 (metabolism)
• Integrin beta Chains (metabolism)
• Interferon-gamma (metabolism)
• Membrane Glycoproteins (metabolism)