Immune complex binding by immunocamouflaged [poly(ethylene glycol)-grafted] erythrocytes.
Immune complexes (IC) are constantly formed at low levels in normal individuals. In humans, the red blood cell (RBC) complement receptor 1 (CR1) plays the dominant role in the IC binding and clearance. Over the last several years, we have investigated the potential utility of immunocamouflaged (methoxypoly(ethylene glycol) [mPEG] grafted) RBC to attenuate the risk of alloimmunization. Because the grafted polymer nonspecifically camouflages membrane proteins, its effects on CR1 detection and IC binding were assessed. The dose dependent (0-2.5 mM) effects of activated mPEG (CmPEG, 5 kDa; and BTCmPEG, 5 and 20 kDa) on CR1 detection and the binding of artificially generated IC [C3b coated alkaline phosphatase and antialkaline phosphatase complexes] to control and pegylated RBC was investigated by flow cytometry. In contrast to selected non-ABO blood group antigens, grafted mPEG did not effectively camouflage CR1. Surprisingly, however, even very low grafting concentrations of mPEG (>or=0.3 mM) resulted in a >or=95% loss in IC binding. Further reductions in grafting concentration (0.15 and 0.03 mM mPEG) still yielded decreased IC binding of approximately 60 and 40%, respectively. Importantly, unactivated mPEG had minimal effects on IC binding. These data demonstrate that even small amounts of grafted mPEG interfere with the multivalent CR1-IC interaction necessary for high affinity IC binding, hence large volume transfusions of mPEG-RBC may be contraindicated in patients with pre-existing IC disease. Whether this concern is of clinical significance in healthy humans is less clear due to dilutional effects and the presence of secondary clearance pathways.
Bradley
Amanda J
AJ
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Scott
Mark D
MD
D000017:ABO Blood-Group System / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000276:immunology*; D001787:Blood Group Incompatibility / Q000276:immunology / Q000517:prevention & control*; D017707:Erythrocyte Transfusion / Q000379:methods*; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D011092:Polyethylene Glycols / Q000737:chemistry*; D017463:Receptors, Complement 3b / Q000737:chemistry / Q000276:immunology; D012204:Rh-Hr Blood-Group System / Q000276:immunology
D000017:ABO Blood-Group System; D000936:Antigen-Antibody Complex; C509991:CR1 protein, human; D017463:Receptors, Complement 3b; D012204:Rh-Hr Blood-Group System; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol