In vitro assessment of recombinant, mutant immunoglobulin G anti-D devoid of hemolytic activity for treatment of ongoing hemolytic disease of the fetus and newborn.
BACKGROUND
A specific treatment for ongoing hemolytic disease of the fetus and newborn (HDFN) due to anti-D would be very attractive. One approach could be administration to the mother of nonhemolytic anti-D, which by crossing the placenta can block the binding of hemolytic maternal anti-D.


METHODS
Two anti-D immunoglobulin G3 (IgG3) heavy-chain mutants were expressed in Chinese hamster ovary cells. To investigate whether these anti-D IgG3 mutants could inhibit the red blood cell-destructive activity of recombinant human (rHu)IgG1 with identical antigen-binding region as well as polyclonal anti-D having multiple D epitope specificities, two assays were used, antibody-dependent cell-mediated cytotoxicity (ADCC) and a chemiluminescence (CL)-based method for detection of respiratory burst in peripheral blood monocytes.


RESULTS
The two IgG3 anti-D heavy-chain mutants inhibited the ADCC and CL responses mediated by a rHuIgG1 anti-D with identical antigen-binding region as the mutant antibodies, as well as the destructive activity mediated by a polyclonal anti-D.


CONCLUSIONS
The use of nonhemolytic anti-D may be an effective countermeasure against hemolysis in HDFN due to anti-D.
Nielsen
Leif K
LK
H:S Blodbank KI2034, Department of Clinical Immunology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark. lkn@rh.regionh.dk
Green
Trine H
TH
Sandlie
Inger
I
Michaelsen
Terje E
TE
Dziegiel
Morten H
MH
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004899:Erythroblastosis, Fetal / Q000188:drug therapy*; D005260:Female; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D007074:Immunoglobulin G; D007167:Immunotherapy / Q000379:methods; D008163:Luminescent Measurements; D009000:Monocytes; D009154:Mutation; D011994:Recombinant Proteins; D016897:Respiratory Burst / Q000187:drug effects; D018029:Rho(D) Immune Globulin / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use*
D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D018029:Rho(D) Immune Globulin