Neutralization of blood group A-antigen by a novel anti-A antibody: Overcoming ABO-incompatible solid-organ transplantation

Yasushi Hasegawa, Yukinari Kato, Mika Kato Kaneko, Satoshi Ogasawara, Motohide Shimazu, Minoru Tanabe, Shigeyuki Kawachi, Hideki Obara, Masahiro Shinoda, Yuko Kitagawa, Hisashi Narimatsu, Masaki Kitajima

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background. The major barrier to ABO-incompatible solid-organ transplantation is acute humoral rejection. It is known to be triggered by antidonor blood group A/B antibodies, which might bind to A/B-antigen on the endothelium of the graft. Various strategies to reduce antiblood group antibody by overcoming ABO-incompatible transplantation have been tried. However, antigen-suppressing procedures have not been performed. Methods. We produced a novel anti-A antibody (K7508) by immunizing mice with salivary mucin of a blood group A individual, thereby clarifying that blood group A-antigen is expressed in endothelial cells of the liver. We investigated whether K7508 can mask A-antigen on the cells in vitro. Next, we immunized mice with A-antigen-expressing cells coated with K7508 or its Fab fragment, and measured anti-A antibody production in the mice. Results. Blood group A-antigen-expressing cells, such as blood group A-red blood cells (A-RBCs) and A431 cells, coated with K7508 were not recognized by another anti-A antibody in flow cytometry, indicating that A-antigen was masked by K7508 in vitro. The A-antigen on the paraffin-embedded liver tissue was also masked by K7508. Furthermore, the production of anti-A antibody in mice immunized with A-antigen-expressing cells coated with K7508 or its Fab fragment was significantly suppressed compared to that in mice immunized with non-coated cells alone, indicating that A-antigen was neutralized by K7508 in vivo. Conclusions. The neutralization of blood group antigen by antiblood group antibody and especially its Fab fragment might represent one strategy to overcome ABO-incompatible organ transplantation.

Original languageEnglish
Pages (from-to)378-385
Number of pages8
JournalTransplantation
Volume85
Issue number3
DOIs
Publication statusPublished - 2008 Feb 1
Externally publishedYes

Keywords

  • ABO-incompatible organ transplantation
  • Antiblood group antibody
  • Fab fragment
  • Neutralization of blood group antigen

ASJC Scopus subject areas

  • Transplantation

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    Hasegawa, Y., Kato, Y., Kaneko, M. K., Ogasawara, S., Shimazu, M., Tanabe, M., Kawachi, S., Obara, H., Shinoda, M., Kitagawa, Y., Narimatsu, H., & Kitajima, M. (2008). Neutralization of blood group A-antigen by a novel anti-A antibody: Overcoming ABO-incompatible solid-organ transplantation. Transplantation, 85(3), 378-385. https://doi.org/10.1097/TP.0b013e3181612f84