title: Polymer-mediated immunocamouflage of red blood cells: effects of polymer size on antigenic and immunogenic recognition of allogeneic donor blood cells.
abstract: Developing a practical means of reducing alloimmunization in chronically transfused patients would be of significant clinical benefit. Immunocamouflaging red blood cells (RBCs) by membrane grafting of methoxypoly(ethylene glycol) (mPEG) may reduce the risk of allo-immunization. The results of this study showed that antibody recognition of non-ABO antigens was significantly reduced in an mPEG-dose- and polymer size-dependent manner, with higher molecular weight mPEGs providing better immunoprotection. Furthermore, in vivo immunogenicity was significantly reduced in mice serially transfused with mPEG-modified xenogeneic (sheep; sRBCs), allogeneic (C57Bl/6), or syngeneic (Balb/c) RBCs. Following a primary transfusion of sRBCs, mice receiving mPEG-sRBCs showed a >90% reduction in anti-sRBC IgG antibody levels. After two transfusions, mice receiving mPEG-sRBCs showed reductions of >80% in anti-sRBC IgG levels. Importantly, mPEG-modified autologous cells did not induce neoantigens or an immune (IgG or IgM) response. These data suggest that the global immunocamouflage of RBCs by polymer grafting may provide a safe and cost-effective means of reducing the risk of alloimmunization.
authors.affiliation: Canadian Blood Services, Vancouver, V6T 1Z3, British Columbia, Canada.
authors.forename: DunCheng
authors.initials: D
authors.lastname: Wang
authors.forename: Dana L
authors.initials: DL
authors.lastname: Kyluik
authors.forename: Kari L
authors.initials: KL
authors.lastname: Murad
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Toyofuku
authors.forename: Mark D
authors.initials: MD
authors.lastname: Scott
mesh_terms: D000371:Agglutination; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001782:Blood Donors; D001789:Blood Group Antigens / Q000276:immunology*; D004337:Drug Carriers / Q000737:chemistry; D017707:Erythrocyte Transfusion / Q000379:methods; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry*; D012756:Sheep; D014184:Transplantation, Homologous
chemical_list: D001789:Blood Group Antigens; D004337:Drug Carriers; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol