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1.
MAbs ; 6(3): 783-93, 2014.
Article in English | MEDLINE | ID: mdl-24594862

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.


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