Decreased immunorejection in unmatched blood transfusions by attachment of methoxypolyethylene glycol on human red blood cells and the effect on D antigen

Tan, Yunlong; Qiu, Yan; Xu, Hua; Ji, Shou‐Ping; Li, Su-Bo; Gao, Feng; Zhang, Yang-Pei

doi:10.1111/j.1537-2995.2006.01038.x

Cited by 19 publications

(16 citation statements)

References 16 publications

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“…Identification of some blood group antigens at the surface of cells to be infused and determination of the immunohematologic status of the recipient serum are crucial procedures before transfusion. With the aim of producing a universal RBC population that can be used regardless of the recipient's ABO blood group phenotype, previous research has focused on masking AB antigens through polyethylene glycol (PEG) treatment of the cells or on erasing the AB epitopes using glycosidases 1,2 . However, these strategies are of limited scope and cannot be used to silence blood group phenotypes other than AB or impose a specific blood group antigen on the cells.…”

mentioning

confidence: 99%

A genetic strategy to control expression of human blood group antigens in red blood cells generated in vitro

Bagnis¹,

Chapel²,

Chiaroni³

et al. 2009

Transfusion

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In this work focusing on the Kidd blood group system that relies on expression of hUT-B1 glycoprotein under the Jk(a) or Jk(b) antigenic configurations, we demonstrated that hematopoietic progenitors could be genetically modified to exhibit a chosen Kidd phenotype. Beyond production of atypical Kidd phenotypes, this genetic strategy could allow generation of rare blood phenotypes from hematopoietic stem cells regardless of initial donor phenotype. Potential applications for genetically modified blood include production of control samples for immunohematologic testing and for resolution of antibody detection in multiply transfused patients.

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mentioning

confidence: 99%

A genetic strategy to control expression of human blood group antigens in red blood cells generated in vitro

Bagnis¹,

Chapel²,

Chiaroni³

et al. 2009

Transfusion

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“…Although RBC PEGgylation is useful for some blood group antigen coverage, the ABO blood group antigens A and B have been difficult to mask (16–19). Interestingly, monomethyl polyethylene glycol has been shown to be stably attached to RBC membranes for 30 days, even in the case of hemolysis (20). In light of this finding, the 30-day allograft survival observed in NB-LVF4-treated kidneys in this study may reflect the duration bioengineered materials are retained on cell membranes before degradation.…”

Section: Discussionmentioning

confidence: 99%

Pretransplant Kidney-Specific Treatment to Eliminate the Need for Systemic Immunosuppression

Brasile

Glowacki²,

Castracane³

et al. 2010

Transplantation

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Background. Despite significant side effects, chronic systemic immunosuppression remains the backbone of clinical transplantation. We investigated the feasibility of preventing early allorecognition in canine renal allografts using a nonsystemic pretreatment. Methods. The renal vasculature was treated with a bioengineered interface consisting of a nano-barrier membrane during 3 hr of ex vivo warm perfusion. Results. Preliminary feasibility of the immunocloaking technology was established by the following criteria: it is possible to achieve approximately 90% coverage of the vasculature with nano-barrier membrane after 3 hr of ex vivo warm perfusion; covering the luminal surfaces prevents allorecognition as determined by mixed lymphocyte-vascular endothelial reaction; covering the luminal surfaces does not negatively affect renal function as determined by auto-transplant outcomes; and graft rejection is significantly postponed in canine kidneys treated with the immunocloaking technology. In the absence of systemic immunosuppression, untreated control dogs experienced a mean onset of rejection on day 6, whereas in the treated dogs with modified renal vascular luminal surfaces, the mean onset of rejection was significantly delayed until day 30. Conclusions. The ability to postpone, or eventually eliminate, the allorecognition that occurs immediately on reper-fusion could provide a new window of opportunity to introduce adjunct therapies to support tolerance induction. To our knowledge, this is the first time significantly prolonged canine renal allograft survival has been achieved in the absence of systemic immunosuppression or immunologic manipulation of the recipient.

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“…This methodology allows the modeling of a second-order polynomial equation that defines the process. The nonlinear model obtained with statistical Design Expert (version 7.0.0, Stat-Ease, Inc.) is as follows: Y = b 0 +∑b i X i + ∑b ii X 2 i + ∑b ij X ij (1), where Y is the predicted response, X i shows the independent variable, b 0 is an intercept, bi is the linear effect, b ii is the squared effect, and b ij shows the interaction effect.…”

Section: Central Composite Designmentioning

confidence: 99%

“…Red blood cells (RBCs) are the simplest transfused allogeneic cells (1). The membrane of RBCs architecturally contains complex structures that carry defined polymorphic epitopes, identified serologically as blood group antigens.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Camouflage of Major and Minor Antigens on Red Blood Cell Surface With Activated mPEGs

2014

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Background: Host immune system response against blood group antigens is a major problem in blood transfusions, especially for thalassemic patients. Thus, an approach was proposed coating the red blood cell (RBC) surface by polyethylene glycol. Objectives: This study aimed to obtain the optimal simultaneous camouflage of the major and minor antigens by activated methoxy polyethylene glycol (mPEG) with succinimidyl valerate (SVA) and succinimidyl carbonate (SC), separately. Materials and Methods:The degree of RBC agglutination by antibodies against the major and minor blood groups was used as a surrogate measurement for quantitative assessment of the effectiveness of the surface coating. Also, the RBC morphology was assessed using scanning electron microscope (SEM). In addition, to evaluate the host immune system response, the PEGylated RBCs were transferred between two different mouse strains. Results: Statistical analysis of the results demonstrated that the optimal reaction conditions for simultaneous coating of the antigens by mPEG-SVA and mPEG-SC are as mPEG 20 in the polymer mixture, 91.2 and 90.0%, and polymer concentration, 17.21 and 19.80 mg.mL -1 , respectively. However, according to the SEM results, the maximum polymer concentration of 14.5 mg.mL -1 was suggested as the best condition for mPEG-SVA modified human RBCs. Conclusions: It is concluded that the membrane PEGylation camouflages the blood group antigens. This effect is observed significantly for non-ABO/Rh(D) antigens. Also, it is found that the mPEG-SVA provide better coverage than mPEG-SC. The results of in vivo analysis showed that the immune reactions against PEGylated RBCs were considerably reduced, so that the levels of the relevant biochemical parameters in serum were similar to those of the normal hosts 24 hours after transfusion.

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Decreased immunorejection in unmatched blood transfusions by attachment of methoxypolyethylene glycol on human red blood cells and the effect on D antigen

Abstract: In conclusion, mPEG-RBCs have acceptable in vitro properties and provide a useful solution to problems with clinical blood matching, although such masking leaves much to be desired.

Cited by 19 publications

References 16 publications

A genetic strategy to control expression of human blood group antigens in red blood cells generated in vitro

A genetic strategy to control expression of human blood group antigens in red blood cells generated in vitro

Pretransplant Kidney-Specific Treatment to Eliminate the Need for Systemic Immunosuppression

Simultaneous Camouflage of Major and Minor Antigens on Red Blood Cell Surface With Activated mPEGs

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