title: Immunogenicity of murine mPEG-red blood cells and the risk of anti-PEG antibodies in human blood donors.
abstract: The immunocamouflage of non-ABO blood group antigens by membrane-grafted methoxypoly(ethylene glycol) (mPEG) may attenuate the risk of red blood cell (RBC) alloimmunization. However, concerns have been raised over the immunogenic risk of PEG and PEG-RBCs. To assess this risk, murine and human studies were performed. Mice were exposed to soluble PEG prior to, or between, multiple transfusions (∼60-day intervals) of control or mPEG-RBCs, and cell survival was determined by flow cytometry. In some studies, the control and mPEG-RBC groups were reversed after one or more transfusions. Furthermore, human blood donors and commercial intravenous immunoglobulin products were examined to detect anti-PEG antibodies and to assess the risk for false positives. Naïve mice receiving chronic mPEG-RBC transfusions had normal RBC survival curves with no evidence of anti-PEG antibodies. Similarly, challenge with soluble PEG did not elicit anti-PEG antibodies in mice. Studies in humans revealed no evidence of a high prevalence of anti-PEG antibodies in either blood donors or commercial intravenous immunoglobulin. However, by use of the methods employed by studies identifying high levels of anti-PEG antibodies, a significant level (∼15%) of "false positives" were detected in commercial antibodies of known (non-PEG) specificities. These findings suggest that methodologic problems yielded a high rate of false positives in these earlier studies. These data continue to support the clinical utility of cellular PEGylation and the low immunogenic risk of grafted mPEG.
authors.affiliation: Canadian Blood Services, Vancouver, BC, Canada; Canadian Nuclear Laboratories, Chalk River, ON, Canada.
authors.forename: Yevgeniya
authors.initials: Y
authors.lastname: Le
authors.affiliation: Canadian Blood Services, Vancouver, BC, Canada; Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Toyofuku
authors.affiliation: Canadian Blood Services, Vancouver, BC, Canada; Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address: mdscott@mail.ubc.ca.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Scott
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D001782:Blood Donors; D002470:Cell Survival / Q000276:immunology; D017707:Erythrocyte Transfusion / Q000009:adverse effects; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000276:immunology; D051379:Mice; D023421:Models, Animal; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000737:chemistry; D013997:Time Factors
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol