Interactions of IgM ABO antibodies and complement with methoxy-PEG-modified human RBCs

Transfusion
A J BradleyMark D Scott

Abstract

RBCs modified with cyanuric chloride activated methoxy-PEG (CmPEG; 5000 Da) are less immunogenic than untreated RBCs, and their use thus may reduce the risk of alloimmunization in chronically transfused patients. To further examine the potential utility of CmPEG-RBCs, the effects of derivatization on an arm of the immune system that plays an important role in transfusion rejection-the complement system--were determined. When CmPEG-RBCs were incubated in autologous or heterologous ABO-matched serum, no classical or alternative pathway consumption was found, no C3a was generated, no cell-bound C3b or C9 was detected, and no cell lysis occurred. Cell-bound complement regulation was normal for CmPEG-RBCs, as determined by acidified serum or reactive lysis assays. CmPEG-RBCs differed from control RBCs only when incubated in ABO-mismatched serum. In that case, CmPEG modification failed to protect against ABO antibody-dependent complement-mediated lysis. Indeed, cell lysis was actually enhanced at CmPEG concentrations >1.0 mM. The enhanced lysis of CmPEG-RBCs in ABO-mismatched serum correlated with increased IgM binding and C3a generation and elevated C3b and C9 membrane deposition. While PEG modification effectively blocks non-ABO an...Continue Reading

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Citations

Feb 26, 2004·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·Mark D Scott, Audrey M Chen
Feb 13, 2003·Pediatric Clinics of North America·Keith C Quirolo
Feb 13, 2003·Drug Discovery Today·A Christy Hunter, S Moein Moghimi
Mar 6, 2003·Vox Sanguinis·George Garratty
Mar 28, 2013·Journal of Drug Delivery·Stefano Salmaso, Paolo Caliceti
Mar 3, 2010·Expert Opinion on Drug Delivery·Vladimir R Muzykantov
Mar 17, 2007·Artificial Cells, Blood Substitutes, and Immobilization Biotechnology·Parimala NacharajuSeetharama A Acharya
Nov 26, 2015·Acta Biomaterialia·Vincent L Leung, Jayachandran N Kizhakkedathu
Sep 3, 2011·Biomaterials·Duncheng WangMark D Scott
Mar 20, 2014·ACS Nano·Lara K BogartRaphaël Lévy
Oct 21, 2003·Journal of Biomedical Materials Research. Part a·Audrey M Chen, Mark D Scott
Jul 27, 2007·American Journal of Hematology·Amanda J Bradley, Mark D Scott
Sep 30, 2006·Biotechnology and Bioengineering·Sharon I Gundersen, Andre F Palmer
Jan 8, 2011·British Journal of Haematology·Claude BagnisPascal Bailly
Mar 7, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Tatsuhiro IshidaHiroshi Kiwada
May 9, 2002·Biochimica Et Biophysica Acta·Amanda J BradleyMark D Scott
Sep 11, 2014·Drug Discovery Today·Johan J F VerhoefHuub Schellekens
Nov 26, 2002·Hematology·George GarrattyLawrence D Petz
Jul 1, 2006·Artificial Cells, Blood Substitutes, and Immobilization Biotechnology·Audrey M Chen, Mark D Scott
Apr 14, 2020·Angewandte Chemie·Derek C Church, Jonathan K Pokorski
Aug 18, 2020·Macromolecular Rapid Communications·Maria C Arno
Dec 21, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Srinivas AbbinaJayachandran N Kizhakkedathu
Nov 12, 2018·ACS Biomaterials Science & Engineering·Srinivas AbbinaJayachandran N Kizhakkedathu

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