The role of antibodies in dysfunction of pig-to-baboon pulmonary transplants

Objective: Pulmonary transplantation has become the preferred treatment for end-stage lung disease, but application of the procedure is limited becaus e of a paucity of donors. One way to solve donor limitations is to use anim al organs as a donor source or xenotransplantation. The current barrier to pulmonary xenotransplantation is the rapid failure of the pulmonary xenogra ft. Although antibodies are known to play a role in heart and kidney xenogr aft rejection, their involvement in lung dysfunction is less defined. This project was designed to define the role of antibodies in pulmonary graft re jection in a pig-to-baboon model. Methods: Orthotopic transgenic swine left lung transplants were performed i n baboons depleted of antibodies by one of three techniques before transpla ntation: (1) ex vivo swine kidney perfusion, (2) total immunoglobulin-deple ting column perfusion, and (3) ex vivo swine lung perfusion. Results were c ompared with those of transgenic swine lung transplants in unmodified baboo ns. Results: All three techniques of antibody removal resulted in depletion of xenoreactive antibodies. Only pretransplantation lung perfusion improved pu lmonary xenograft function compared with lung transplantation in unmodified baboons. Conclusions: The pathogenesis of pulmonary injury in a swine-to-primate tra nsplant model is different from that in renal and cardiac xenografts. Deple tion of antibodies alone does not have a beneficial effect and may actually be detrimental.