Depletion of natural antibodies in non-human primates--a step towards successful discordant xenografting in humans.

There is evidence to suggest that long-term survival of discordant xenografts may be possible if the organ is transplanted at a time when the host natural anti-species (xenoreactive) antibodies are temporarily absent or otherwise inhibited from reacting with the donor antigens. There is also evidence that the target antigens on pig organs may be carbohydrate structures, as are the human A and B blood group antigens. The intravenous infusion of synthetic A or B trisaccharides in hyperimmunized baboons, coupled with pharmacologic immunosuppression, has prolonged ABO-incompatible cardiac allograft survival from a mean of 19 minutes to several days, and even to several weeks in one animal. The nature of the carbohydrate structures of the pig antigens against which human xenoreactive antibodies are directed has been investigated. Two of the most important of these would appear to be alpha galactosyl structures, referred to as linear B. If the central role of these carbohydrates can be confirmed, then it may be possible to adsorb out or inhibit human anti-pig antibodies in the same way as anti-A and anti-B antibodies. It may then be possible to offer organ transplantation to all suitable recipients under elective conditions without the restriction of donor availability.