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Neutralization of Blood Group A-Antigen by a Novel Anti-A Antibody: Overcoming ABO-Incompatible Solid-Organ Transplantation

2008; Wolters Kluwer; Volume: 85; Issue: 3 Linguagem: Inglês

10.1097/tp.0b013e3181612f84

1534-6080

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

Transplantation: Methods and Outcomes

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.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.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.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.