Reduced red blood cell destruction by antibody fragments.
Antibodies to blood group antigens can cause immune RBC destruction directly (extravascular destruction) or indirectly through subsequent complement activation (intravascular hemolysis). The Fc portion of the IgG antibody is responsible for the effector functions of immune RBC destruction. We hypothesized that sensitization of RBCs with blood group antigen-specific IgG antibodies lacking their Fc portion would escape from the recipient's immune system, allowing for a longer survival period of the RBCs in the circulation. Direct injection of mouse RBC-specific Ter-119 monoclonal antibody into mice resulted in a more severe anemia compared with that in mice injected with the Ter-119 F(ab')2 fragment. We found that mouse RBCs coated in vitro with the Ter-119 F(ab')2 fragment, when transfused into mice, survived longer in circulation compared with RBCs coated with whole Ter-119 IgG molecule. The data support the conclusion that antibodies can be rendered less pathogenic through removal of their Fc portion.
Department of Complement Biology, New York Blood Center, New York, NY, USA.
A
A
Mqadmi
S
S
Abramowitz
X
X
Zheng
K
K
Yazdanbakhsh
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology; D006461:Hemolysis / Q000187:drug effects*; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage* / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D051379:Mice
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments