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Removal of blood group A/B antigen in organs by ex vivo and in vivo administration of endo-ß-galactosidase (ABase) for ABO-incompatible transplantation

2008; Elsevier BV; Volume: 20; Issue: 3 Linguagem: Inglês

10.1016/j.trim.2008.09.007

1878-5492

Takaaki Kobayashi, DaGe Liu, Haruko Ogawa, Yuko Miwa, Takaharu Nagasaka, Shoichi Maruyama, Yu‐Teh Li, Akira Ōnishi, Masaki Iwamoto, Takafumi Kuzuya, Kenji Kadomatsu, Kazuharu Uchida, Akimasa Nakao,

Pancreatic function and diabetes

ABO incompatibility in organ transplantation is still a high risk factor for antibody-mediated rejection, despite the progress in effective treatments. We have explored the possibility of using the enzyme to remove the blood type A/B antigen in organs. Recombinant endo-ß-galactosidase (ABase), which releases A/B antigen, was produced in E. coli BL-21. Human A/B red blood cells (RBC) were digested with ABase, and subjected to flow cytometric analysis after incubation with human sera. Purified recombinant ABase was intravenously administered to a baboon. Biopsies were taken from kidney and liver before and 1, 4 and 24 h after in vivo administration. Excised baboon kidneys were perfused with cold UW solution +/− purified recombinant ABase and preserved at 4 °C. Biopsies were taken before and 1 and 4 h after ex vivo perfusion. The change in A/B antigen expression was analyzed by immunohistochemical study. ABase removed 82% of A antigen and 95% of B antigen in human A/B red blood cells, and suppressed anti-A/B antibody binding and complement activation effectively. ABase was also found to remain active at 4 °C. In vivo infusion of ABase into a blood type A baboon demonstrated a marked reduction of A antigen expression in the glomeruli of kidney (85% at 1 h, 9% at 4 h and 13% at 24 h) and the sinusoids of liver (47% at 1 h, 1% at 4 h and 3% at 24 h) without serious adverse effects. After ex vivo perfusion and cold storage of excised baboon kidney (blood type B) with ABase, the expression levels of B antigen in glomeruli were reduced to 49% at 1 h and 6% at 4 h. This alternative approach might be useful for minimizing antibody removal and anti-B cell immunosuppression as an adjuvant therapy in ABO-incompatible kidney, liver and possibly heart transplantation.