Rebound in complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxic activity in primate serum after pig liver perfusion

HYPERACUTE REJECTION (HAR) of xenograft is initiated by humoral mechanisms including the recipient's xenoreactive natural antibodies (XNA) and complement proteins (C). The role of immunoglobulin M (IgM) XNA in xenograft rejection has been extensively studied and seems essential in C activation. 1,2 In vitro, porcine endothelial cells are killed by complement-dependent cytotoxicity (CDC) after the binding of IgM XNA. The role of IgG XNA is less well known. In vitro, IgG XNA in cooperation with human lymphocytes are able to kill porcine endothelial cells by an antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. The elimination of the recipient's XNA is one of the possible strategies to overcome HAR. We have performed extracorporeal perfusion of a pig organ by primate's blood or plasma and obtained the removal of 60% to 70% of the recipient's XNA. 3 This article studies the induced immune response in primates after extracorporeal pig liver perfusion.