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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
Author(s) -
Nielsen Leif K.,
Green Trine H.,
Sandlie Inger,
Michaelsen Terje E.,
Dziegiel Morten H.
Publication year - 2008
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2007.01474.x
Subject(s) - polyclonal antibodies , antibody dependent cell mediated cytotoxicity , antibody , epitope , chinese hamster ovary cell , hemolysis , antigen , microbiology and biotechnology , biology , recombinant dna , cytotoxicity , immunology , in vitro , monoclonal antibody , receptor , biochemistry , gene
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. STUDY DESIGN AND 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. CONCLUSION: The use of nonhemolytic anti‐D may be an effective countermeasure against hemolysis in HDFN due to anti‐D.