Development of the new strategy in ABO blood group incompatible transplantation

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The major barrier to ABO-incompatible solid organ transplantation is the acute humoral rejection, leading to graft dysfunction. Humoral rejection associated with ABO-incompatible, transplantation is triggered by antidonor blood group A/B antibodies that bind to the endothelium of the donor's organ.We tried to develop the new methods of neutralizing the blood group antigen to overcome ABO-incompatible transplantation, which were performed by (1) RNA interference or (2) glycosidases.(1) Firstly, small interference RNA for the ABO blood group gene was created. When the cancer cell lines SW620, LoVo, and SW48 which express A or B antigen were transfected with the small interference RNA, the messenger RNA of the ABO blood group gene were reduced by 70-80%, detected by real time RT-PCR. However, expression of the ABO blood group antigen was not suppressed by small interference RNA, detected by flow cytometry and westernblotting.(2) Blood group A antigen was not completely degraded by α-N-acetylgalactosaminidase. On the other hand, B antigen was degraded by α-galactosidase, and group B RBCs were converted to group B RBCs, which were detected by flow cytometry. The group AB RBCs reacted with α-galactosidase were converted to group A RBCs. The cancer cell line SW48 which have A and B antigens were also converted to the cells with only A antigens by α-galactosidase.We succeeded in neutralizing the blood group B antigen by glycosidase.