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Anti-CD4 monoclonal antibody administration in renal transplanted patients

1990; Academic Press; Volume: 56; Issue: 3 Linguagem: Inglês

10.1016/0090-1229(90)90152-g

1090-2341

Patricia Morel, Claude Vincent, G Cordier, Géneviève Panaye, E Carosella, Jean‐Pierre Revillard,

Complement system in diseases

Administration of anti-CD4 antibodies in rodents was shown to prevent or to reverse spontaneous or experimentally induced autoimmune diseases and to delay organ or skin allograft rejection. Some anti-human CD4 antibodies were shown to be immunosuppressive when injected in monkeys. BL4, and IgG2a anti-human CD4 murine monoclonal antibody, which binds to an epitope located between the two N-terminal domains of the CD4 molecule, was administered to 12 recipients of a renal cadaver allograft, in association with azathioprine (2.5 mg/kg/day) and prednisolone (1 mg/kg/day). Treatment was started 1 day after transplantation and was discontinued after 3 to 14 days (median 5 days). Infusion of 10 or 15 mg of BL4 over 1 hr induced a selective but transient CD4+ lymphocytopenia. The lack of clinical side effect was remarkable. Acute rejection occurred in 4 out of 12 treated patients. Antibody response to BL4 3 weeks after completion of the treatment was demonstrated in only one patient. Residual antibody concentrations in serum, 24 hr after infusion, ranged from 0.1 to 0.5 microgram/ml, that is below the concentration required to achieve 50% inhibition of allogenic mixed lymphocyte reaction in vitro (1-10 micrograms/ml) or to saturate CD4 binding sites (5-10 micrograms/ml). Rapid degradation and dissociation of cell bound BL4 contributed to the failure to achieve high residual serum levels of the antibody.