期刊
BIOMATERIALS
卷 33, 期 10, 页码 3002-3012出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.12.041
关键词
Immunomodulation; Methoxypoly(ethylene glycol); Allogeneic cell; Red blood cell; Antigenicity; RhD
资金
- Canadian Blood Services, Canadian Blood Services-Canadian Institutes of Health Research (CBS-CIHR)
- Health Canada
- Canada Foundation for Innovation
- Michael Smith Foundation for Health Research at the University of British Columbia Centre for Blood Research
Red blood cell (RBC) transfusions are an important clinical intervention. However, RBC express hundreds of non-ABO antigens making alloimmunization a significant risk. RhD expression is the most immunologically important non-ABO antigen. Availability of RhD blood, often problematic in North America and Europe, is a significant issue in Asia and Africa where RhD blood is uncommon (<0.5% of supply). The immunocamouflage of RhD is readily accomplished by the covalent grafting of methoxypoly(ethylene glycol) [mPEG] to the RBC membrane. To determine if RhD immunocamouflage would inhibit its immunologic recognition, an in vitro RhD-sensitized antigen presentation assay using PBMC and dendritic cells (DC) from RhD-sensitized women was used. The immunological effects of polymer grafting to an immunoclominant RhD peptide, purified RhD protein and intact RhD+ RBC were examined via T cell proliferation and cytokine release assays. At Day 11, PEGylation significantly attenuated T cell proliferation arising from RhD peptide (similar to 80 -> 5%), protein (36 -> 0.2%) and intact RBC (33 -> 1.4%). Cytokine secretion was similarly blunted following PEGylation of the purified protein or intact RBC. These data support the immunomodulatory effects of PEGylation and the potential utility of this technology in transfusion medicine - especially in situations where RhD- blood is rare or in short supply. (C) 2011 Elsevier Ltd. All rights reserved.
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