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J Immunol. 2014 Sep 15;193(6):2902-10. doi: 10.4049/jimmunol.1302287. Epub 2014 Aug 13.

Antibody-mediated immune suppression of erythrocyte alloimmunization can occur independently from red cell clearance or epitope masking in a murine model.

Author information

  • 1The Canadian Blood Services, Ottawa, Ontario K1G 4J5, Canada; Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, 430030 Wuhan, China; Department of Laboratory Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada;
  • 2Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
  • 3The Canadian Blood Services, Ottawa, Ontario K1G 4J5, Canada; Department of Laboratory Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada;
  • 4Department of Laboratory Medicine, Yale University, New Haven, CT 06520;
  • 5Puget Sound Blood Center Research Institute, Seattle, WA 98102;
  • 6Department of Laboratory Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada;
  • 7Kanto-Koshinetsu Block Blood Center, Japanese Red Cross, Koto-ku, Tokyo, Japan 135-8639;
  • 8The Canadian Blood Services, Ottawa, Ontario K1G 4J5, Canada; Department of Laboratory Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada; Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A1, Canada; and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A1, Canada lazarusa@smh.ca.

Abstract

Anti-D can prevent immunization to the RhD Ag on RBCs, a phenomenon commonly termed Ab-mediated immune suppression (AMIS). The most accepted theory to explain this effect has been the rapid clearance of RBCs. In mouse models using SRBC, these xenogeneic cells are always rapidly cleared even without Ab, and involvement of epitope masking of the SRBC Ags by the AMIS-inducing Ab (anti-SRBC) has been suggested. To address these hypotheses, we immunized mice with murine transgenic RBCs expressing the HOD Ag (hen egg lysozyme [HEL], in sequence with ovalbumin, and the human Duffy transmembrane protein) in the presence of polyclonal Abs or mAbs to the HOD molecule. The isotype, specificity, and ability to induce AMIS of these Abs were compared with accelerated clearance as well as steric hindrance of the HOD Ag. Mice made IgM and IgG reactive with the HEL portion of the molecule only. All six of the mAbs could inhibit the response. The HEL-specific Abs (4B7, IgG1; GD7, IgG2b; 2F4, IgG1) did not accelerate clearance of the HOD-RBCs and displayed partial epitope masking. The Duffy-specific Abs (MIMA 29, IgG2a; CBC-512, IgG1; K6, IgG1) all caused rapid clearance of HOD RBCs without steric hindrance. To our knowledge, this is the first demonstration of AMIS to erythrocytes in an all-murine model and shows that AMIS can occur in the absence of RBC clearance or epitope masking. The AMIS effect was also independent of IgG isotype and epitope specificity of the AMIS-inducing Ab.

PMID:
25122924
DOI:
10.4049/jimmunol.1302287
[PubMed - indexed for MEDLINE]
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