Histo-blood Group A Antigen Expression in Pig Kidneys: Implication for ABO Incompatible Pig-to-Human Xenotransplantation

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Abstract
There is a relative shortage of donor organs for clinical transplantation, and the use of animal organs is being considered. A clinical trial was performed connecting pig kidneys to the circulation of a dialysis patient. A pig kidney was, after plasmapheresis, extracorporeally connected to the circulation of a volunteer dialysis patient. The patient was of blood group B and the pig of blood group A. The experiment gave rise to a strong humoral immune response where the xenoantibodies were shown to be of immunoglobulin G (IgG), IgM and IgA immunoglobulin classes, recognizing mainly the Gal alpha1-3Gal epitope and the anti-A antibodies was exclusively of IgM type, recognizing the blood group A trisaccharide. Immunohistological examinations of blood group A pig kidneys revealed that blood group A antigens are located in the distal tubules, thin and thick tubules of Henle and the epithelium of the collecting ducts but absent in proximal tubules, glomeruli, large vessels and capillaries. In the perfused kidney, a patchy destruction of tubular cells was found and these segments stained positive for blood group A antigens and had a codeposition of human IgM antibodies and complement components. Tubular segments which were apparently normal were all negative for blood group A antigens but strongly expressed the Gal alpha1-xenoantigen. In this patient, challenged simultaneously with carbohydrate antigen epitopes representing both the ABO and the xenobarrier, the humoral immune response differed concerning the immunoglobulin classes induced. The low remaining anti-A titre after plasmapheresis was probably sufficient to cause destruction of A antigen-positive tubular cells, while the corresponding Gal alpha1-xenoantigen-positive cells were structurally intact. This case confirms that in future xenotransplantation, matching for the ABO system has to be undertaken in the same way as in human allotransplantation.