Immunogenicity of murine mPEG-red blood cells and the risk of anti-PEG antibodies in human blood donors

Exp Hematol. 2017 Mar;47:36-47.e2. doi: 10.1016/j.exphem.2016.11.001. Epub 2016 Nov 15.

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.

MeSH terms

  • Animals
  • Antibodies / blood
  • Antibodies / immunology*
  • Blood Donors*
  • Cell Survival / immunology
  • Erythrocyte Transfusion / adverse effects
  • Erythrocytes / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulins, Intravenous / immunology
  • Mice
  • Models, Animal
  • Polyethylene Glycols / adverse effects*
  • Polyethylene Glycols / chemistry
  • Time Factors

Substances

  • Antibodies
  • Immunoglobulin G
  • Immunoglobulins, Intravenous
  • Polyethylene Glycols
  • monomethoxypolyethylene glycol

Grant support