Pretreatment of kidney allografts with monoclonal antibodies to CD45: results of a multicentre study. CD45 Study Group.
The perfusion of human renal allografts with CD45-specific monoclonal antibodies (mAbs) may reduce their immunogenicity and the incidence of rejection. We performed a safety study in 40 patients receiving their first cadaveric renal transplant. Two milligrams each of the rat CD45 specific mAbs YTH 24.5 and YTH 54.12 were perfused into the grafts prior to transplantation. The patients were followed for 3 months. No patient died, and four grafts were lost, three to vascular causes not considered to be related to antibody perfusion and one to severe rejection. Two patients developed an anti-rat antibody response. Immunohistological double-labelling performed on cortical biopsies taken post-perfusion and prior to wound closure showed that at least 60% of the CD45+ cells were coated by perfused anti-CD45 ('antibody uptake'). Among the patients studied for uptake and episodes of rejection, the incidence of rejection was 75% in 12 patients whose antibody uptake was < 95% compared with 22% in 18 patients with antibody uptake > or = 95% (P = 0.01). We conclude that this treatment was free of adverse effects and that there is a correlation between the uptake of antibody by passenger leucocytes and reduction in acute rejection episodes.
Addenbrooke's Hospital, Cambridge, UK.
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Goldberg
D000328:Adult; D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D002102:Cadaver; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007668:Kidney / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D051381:Rats; D014019:Tissue Donors; D016896:Treatment Outcome
D000910:Antibodies, Heterophile; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017493:Leukocyte Common Antigens