The clearance kinetics of autologous RhD-positive erythrocytes coated ex vivo with novel recombinant and monoclonal anti-D antibodies.
Anti-D is given routinely to pregnant RhD-negative women to prevent haemolytic disease of the fetus and newborn. To overcome the potential drawbacks associated with plasma-derived products, monoclonal and recombinant forms of anti-D have been developed. The ability of two such antibodies, BRAD-3/5 monoclonal anti-D IgG (MAD) and rBRAD-3/5 recombinant anti-D IgG (RAD), to clear RhD-positive erythrocytes from the circulation was compared using a dual radiolabelling technique. Six RhD-positive males received autologous erythrocytes radiolabelled with (99m)Tc and (51)Cr and coated ex vivo with MAD and RAD. Blood samples were collected up to 1 h following intravenous injection, and percentage dose of radioactivity in the samples determined. Three different levels of coating were used on three separate occasions. No significant differences between MAD and RAD were observed in the initial clearance rate constant at any dose level. The log[activity]-time clearance plots were curved, showing a reduction in the clearance rate constant with time. This reduction was more marked for RAD than for MAD. The results support a dynamic model for the clearance of antibody-coated erythrocytes that may have wider relevance for the therapeutic use of antibodies.
Chapman
G E
GE
Bio Products Laboratory, Elstree, Hertfordshire, UK.
Ballinger
J R
JR
Norton
M J
MJ
Parry-Jones
D R
DR
Beharry
N A
NA
Cousins
C
C
Dash
C H
CH
Peters
A M
AM
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D002860:Chromium Radioisotopes / Q000097:blood; D018592:Cross-Over Studies; D004306:Dose-Response Relationship, Immunologic; D004912:Erythrocytes / Q000276:immunology*; D006461:Hemolysis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D011994:Recombinant Proteins / Q000276:immunology; D012204:Rh-Hr Blood-Group System / Q000097:blood* / Q000276:immunology; D018029:Rho(D) Immune Globulin; D013154:Spleen / Q000276:immunology; D013667:Technetium / Q000097:blood
D000911:Antibodies, Monoclonal; D002860:Chromium Radioisotopes; D007074:Immunoglobulin G; D007518:Isoantibodies; C061961:RHO(D) antibody; D011994:Recombinant Proteins; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; C026410:Rho(D) antigen; D013667:Technetium