Anti-CD4 monoclonal antibody therapy in severe psoriasis.
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.
Morel
P
P
Immunology Laboratory, INSERM U80, CNRS URA 1177, Lyon, France.
Revillard
J P
JP
Nicolas
J F
JF
Wijdenes
J
J
Rizova
H
H
Thivolet
J
J
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000096:biosynthesis; D018949:Antigens, CD1; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007075:Immunoglobulin M / Q000096:biosynthesis; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1; D008431:Maternal-Fetal Exchange; D008875:Middle Aged; D011701:PUVA Therapy; D011247:Pregnancy; D011565:Psoriasis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018949:Antigens, CD1; D017252:CD3 Complex; D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018799:Intercellular Adhesion Molecule-1; D016572:Cyclosporine