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Anti-CD4 monoclonal antibody therapy in severe psoriasis.

Abstract
We report here the treatment of psoriasis, a chronic inflammatory skin disease characterized by uncontrolled keratinocyte proliferation, with BB14, a CD4 murine IgG1 antibody. Three patients with severe psoriasis were treated with anti-CD4 mAb infusions (0.2 mg/kg/day for the first patient, 0.4 mg/kg/day for 2 days and 0.8 mg/kg/day during the following days for the 2 others) for 7 or 8 days, without other therapy. Rapid clinical improvement, with major reduction of the Psoriasis Area Severity Index, was observed during 1 month after treatment. Moderate decreases in CD4+ blood cells occurred in the last two patients but not in the first one. Circulating T cells coated with anti-CD4 mAb were detectable during the first 48 h in the first patient and from day 1/2 to day 7/8 in the two others. The density of CD4 molecules on the surfaces of peripheral blood lymphocytes was decreased in all patients and remained low as long as anti-CD4 mAb was detectable in patient serum. The maximal 24 h residual mAb levels ranged from 0.3 microgram/ml in the first patient to 3.8 and 7.0 microgram/ml in the two others. The three patients produced IgM antibodies against the anti-CD4 mAb at day 7/8 or 15 and two patients had IgG antibodies at day 15. Lesional skin samples demonstrated (1) gradual improvement in parakeratosis, papillomatosis and acanthosis, (2) decreased expression of ICAM-1 and HLA-DR by keratinocytes, (3) an increase in CD1a+ Langerhans cell number, (4) partial decrease in epidermal T cell infiltrate and (5) no major change in the dermal infiltrate composed of CD3+, TcR alpha beta+, CD45Ro+, HLA-DR+ T cells. We conclude that anti-CD4 mAb administration can induce a rapid and major improvement in psoriatic lesions, with immunohistochemical changes different from those induced by cyclosporin A or 8-methoxypsoralen plus long wave UV light (PUVA) therapy. Our data provide strong evidence for a critical role of CD4+ lymphocytes in psoriasis.
AuthorsP Morel, J P Revillard, J F Nicolas, J Wijdenes, H Rizova, J Thivolet
JournalJournal of autoimmunity (J Autoimmun) Vol. 5 Issue 4 Pg. 465-77 (Aug 1992) ISSN: 0896-8411 [Print] England
PMID1384529 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, CD1
  • CD3 Complex
  • CD4 Antigens
  • Cell Adhesion Molecules
  • HLA-DR Antigens
  • Immunoglobulin G
  • Immunoglobulin M
  • Intercellular Adhesion Molecule-1
  • Cyclosporine
Topics
  • Adult
  • Antibodies, Monoclonal (therapeutic use)
  • Antigens, CD (biosynthesis)
  • Antigens, CD1
  • CD3 Complex (biosynthesis)
  • CD4 Antigens (immunology)
  • Cell Adhesion Molecules (biosynthesis)
  • Cyclosporine (pharmacology)
  • Female
  • HLA-DR Antigens (biosynthesis)
  • Humans
  • Immunoglobulin G (therapeutic use)
  • Immunoglobulin M (biosynthesis)
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1
  • Maternal-Fetal Exchange
  • Middle Aged
  • PUVA Therapy
  • Pregnancy
  • Psoriasis (immunology, pathology, therapy)
  • T-Lymphocyte Subsets (immunology)
  • Time Factors

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