title: Inhibition of phagocytic recognition of anti-D opsonized Rh D+ RBC by polymer-mediated immunocamouflage.
abstract: The Rh D antigen posed both a significant clinical risk and inventory supply issue in transfusion medicine. The successful development of the immunocamouflaged RBC has the potential to address both the risk of acute anti-D transfusion reactions and to improve D- blood inventory in geographic locations where D- blood is rare (e.g., China). The immunocamouflage of RBC was mediated by the covalent grafting of methoxy(polyethylene glycol) to the cell membrane thereby obscuring the D protein from the immune system. To determine the potential efficacy of mPEG-D+ RBC in D- recipients, anti-D alloantibodies from previously alloimmunized individuals were utilized. The effects of polymer chain size (2-30 kDa) and grafting concentration (0-4 mM) on antibody binding and erythrophagocytosis were determined using the clinically validated monocyte monolayer assay (MMA) and flow cytometry. The immunocamouflage of D was polymer size and grafting concentration dependent as determined using human anti-D alloantibodies (both pooled [RhoGAM] and single donors). Importantly, the 20 kDa polymer provided excellent immunocamouflage of D and reached a clinically significant level of protection, as measured by the MMA, at grafting concentrations of ≥1.5 mM. These findings further support the potential use of immunocamouflaged RBC to reduce the risk of acute transfusion reactions following administration of D+ blood to D- recipients in situations where D- units are unavailable or supply is geographically constrained.
authors.affiliation: Canadian Blood Services, Ottawa, Ontario, Canada.|Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: LifeShare Blood Centers, Shreveport, Louisiana.|Grifols ImmunoHematology Center, San Marcos, Texas.
authors.forename: Ghislain T
authors.initials: GT
authors.lastname: Noumsi
authors.affiliation: Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yin Yu Eunice
authors.initials: YY
authors.lastname: Kwok
authors.affiliation: LifeShare Blood Centers, Shreveport, Louisiana.|Grifols ImmunoHematology Center, San Marcos, Texas.
authors.forename: Joann M
authors.initials: JM
authors.lastname: Moulds
authors.affiliation: Canadian Blood Services, Ottawa, Ontario, Canada.|Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Scott
mesh_terms: D017707:Erythrocyte Transfusion / Q000379:methods*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D009895:Opsonin Proteins / Q000378:metabolism*; D010586:Phagocytes; D011108:Polymers; D018029:Rho(D) Immune Globulin / Q000276:immunology*
chemical_list: D007518:Isoantibodies; D009895:Opsonin Proteins; D011108:Polymers; C061961:RHO(D) antibody; D018029:Rho(D) Immune Globulin