Relevance of compartmentalization of T-cell subsets for clinical improvement in psoriasis: effect of immune-targeted antipsoriatic therapies

Br J Dermatol. 2008 Jul;159(1):91-6. doi: 10.1111/j.1365-2133.2008.08618.x. Epub 2008 Jul 1.

Abstract

Background: Therapies targeting the T cell-mediated pathology of psoriasis have been found to achieve remarkable clinical improvement and have confirmed the crucial role of the immune system either in peripheral blood (PB) or in skin. No analyses of T-cell counts in both compartments have been conducted in order to confirm or refute the hypothesized shifts between them.

Objectives: To gain more insight in the dynamics of compartmentalization of T cells between PB and lesional skin of patients with psoriasis, in response to immune-targeted antipsoriatic therapies.

Methods: Eighteen patients with psoriasis received either efalizumab (n = 9) or etanercept (n = 9) for 12 weeks. Biopsies were taken for immunohistochemical analysis of T-cell subsets and simultaneously T-cell subsets were isolated from PB specimens by flow cytometry.

Results: The Psoriasis Area and Severity Index declined significantly after 12 weeks of etanercept, but not for efalizumab. After treatment with efalizumab, a significantly decreased number of all T-cell subsets was found in the dermis. In the epidermis, CD4+, CD8+, CD25+, CD45RO+ and CD161+ T-cell subsets were significantly decreased. With respect to etanercept, few significant changes in T-cell subsets were found. The percentage of lymphocytes in PB was significantly elevated after efalizumab treatment regardless of responder status.

Conclusions: Treatment with efalizumab establishes successful recompartmentalization of T-cell subsets with modest clinical efficacy after 12 weeks, whereas in etanercept-treated patients, a significant clinical response is no guarantee for significant changes in T-cell subsets in the different compartments. Reductions in T-cell subsets cannot be used as predictive markers for the clinical response to therapy. Interference with the studied T-cell populations in its own right seems not to be responsible for the clinical efficacy of efalizumab and etanercept.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Dermatologic Agents / therapeutic use*
  • Epidermis / drug effects
  • Etanercept
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Severity of Illness Index
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Dermatologic Agents
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Receptors, Tumor Necrosis Factor
  • Etanercept
  • efalizumab