Xenoantibody Depletion of Human Blood with Normothermic Machine Perfusion of Porcine Kidney and Lung prior to Liver Perfusion
Nikolaos Serifis MD1, Taylor M Coe MD1, Siavash Raigani MD1, Cailah Carroll1, Charles G Rickert MD PhD1, Rudy Matheson1, Danielle Detelich MD1, Wenning Qin PhD2, Yinan Kan PhD2, Jacob Layer PhD2, Michele Youd PhD2, William Westlin PhD2, Luhan Yang PhD2, Agnes Azimzadeh PhD1, James F Markmann MD PhD1
1Division of Transplant Surgery, Massachusetts General Hospital, Boston, MA, USA 2eGenesis, Inc., Cambridge, MA, USA
Background: Triple knock-out (TKO) of 3 major xenoantigens has markedly attenuated hyperacute rejection in xenotransplantation. However, improved outcomes in xenorecipients with lower anti-porcine antibody titers, indicate activity of the remaining antibody to TKO xenograft failure. Therefore, we sought to test the impact of decreasing residual recipient antibody binding gained through antibody adsorption using ex vivo perfusion of en-bloc kidneys or lung prior to normothermic machine perfusion of porcine livers with human blood.
Methods: Livers(n=4), kidneys and lungs were procured from TKO pigs. 2 livers underwent immediate perfusion with human blood, while 2 livers had perfusion of en-bloc kidneys or the right lung first. The kidneys were perfused for 30 minutes and the lungs were perfused for one hour. A crossmatch assay was completed to assess for IgG and IgM antibody reactivity against pig aortic endothelial cells.
Results: Liver perfusion following en-bloc kidney perfusion was sustained for 14 hours and after right lung perfusion, the liver lasted 15 hours. Livers undergoing immediate perfusion lasted for an average of 9 hours. After kidney adsorption, IgG antibody level fell by 35.3% and IgM antibody level fell by 40.8%. After lung adsorption, IgG antibody level fell by 19.7% and IgM antibody level fell by 14.4%.
Conclusion: Antibody depletion by adsorption through another organ is feasible and effective in reducing residual antibody binding, and was associated with prolongation of organ survival during machine perfusion.
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