Immunological and histological evaluation of clinical samples from psoriasis patients treated with anti-CD6 itolizumab

MAbs. 2014 May-Jun;6(3):783-93. doi: 10.4161/mabs.28376. Epub 2014 Mar 4.

Abstract

Psoriasis is a chronic inflammatory disease with a prevalence of approximately 2-3% in the general population. The majority of diagnosed patients have plaque psoriasis, and about 20% have moderate-to-severe disease. Itolizumab, a new monoclonal antibody specific for the CD6 molecule mainly expressed on T lymphocytes, has demonstrated to inhibit in vitro ligand-induced proliferation and pro-inflammatory cytokine production. We assessed the immunological and histopathological effect of the antibody using clinical samples taken from 26 patients with moderate-to-severe psoriasis included in a clinical trial. The precursor frequency of lymphocytes activated with anti-CD2/CD3/CD28 beads, as well as the number of interferon (IFN)-γ-secreting T cells after stimulation, were measured at different time points of the study. Serum cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. Additionally, lymphocyte infiltration and epidermis hyperplasia were studied in five patients. A significant reduction in T cell proliferation capacity and number of IFN-γ-producing T cells was found in treated patients. Serum levels of interleukin-6, tumor necrosis factor and IFN-γ showed an overall trend toward reduction. No anti-idiotypic antibody response was detected. A significant reduction in the epidermis hyperplasia was observed in analyzed patients. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.

Keywords: CD6; anti-idiotypic antibody response; cell proliferation; epidermal hyperplasia; itolizumab; pro-inflammatory cytokines; psoriasis.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Anti-Idiotypic / blood
  • Antibodies, Monoclonal, Humanized / immunology*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antigens, CD / immunology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Cell Proliferation
  • Cytokines / blood
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Male
  • Middle Aged
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • Psoriasis / therapy*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Young Adult

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD6 antigen
  • Cytokines
  • Interferon-gamma
  • itolizumab