Anti-CD4 monoclonal antibody administration in renal transplanted patients.
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.
Morel
P
P
Laboratoire d'Immunolgie, INSERM U 80, CNRS URA 1177, UCBL, Lyon, France.
Vincent
C
C
Cordier
G
G
Panaye
G
G
Carosella
E
E
Revillard
J P
JP
D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000517:prevention & control; D015704:CD4 Antigens / Q000032:analysis / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D007958:Leukocyte Count; D008214:Lymphocytes / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens