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[Natural human anti-pig agglutinins. Role in the hyperacute rejection of xenogeneic graft in the pig-human donor-recipient combination].

Binding of human natural xenoantibodies to the graft endothelial cells is considered as one of the initial steps in the hyperacute rejection of a pig liver by human. In addition to binding to endothelial cells, human xenoantibodies also agglutinate pig red blood cells. We have therefore compared the anti-pig hemagglutinin titers with the cytotoxic activity to pig endothelial cells of a series of human sera. In order to determine the localisation of the human xenoantibodies fixation in the pig liver, we have studied by immunoperoxidase staining, deposits of IgG, IgM and IgA, using an ex vivo model of isolated pig liver perfused with human blood. Moreover, we have measured hemagglutinin titers in the perfusate along the perfusion. We have found a strong correlation between the anti-pig hemagglutinin titers and the anti-pig endothelial cell cytotoxic activity of human serum. Anti-pig hemagglutinin become undetectable in the perfusate within 4 minutes of perfusion of the pig liver with human blood. The sinusoids in the pig liver were the only structures with positive peroxidase staining. It is therefore suggested that human anti-pig hemagglutinins are in great part the same than human anti-pig endothelial cell cytotoxic antibodies. Pig red blood cells could be used to easily detect anti-pig xenoantibodies in human, and to adsorb xenoantibodies from the recipient before a xenograft.