The Sda and Cad glycan antigens and their glycosyltransferase, β1,4Gal NA cT‐II, in xenotransplantation

Abstract

Antibody‐mediated rejection is a barrier to the clinical application of xenotransplantation, and xenoantigens play an important role in this process. Early research suggested that N‐acetyl‐D‐galactosamine (Gal NA c) could serve as a potential xenoantigen. Gal NA c is the immunodominant glycan of the Sda antigen. Recently, knockout of β1,4‐N‐acetylgalactosaminyltransferase 2 (β1,4Gal NA cT‐II) from the pig results in a decrease in binding of human serum antibodies to pig cells. It is believed that this is the result of the elimination of the Gal NA c on the Sda antigen, which is catalyzed by the enzyme, β1,4Gal NA cT‐II. However, research into human blood group antigens suggests that only a small percentage (1%‐2%) of people express anti‐Sda antibodies directed to Sda antigen, and yet a majority appear to have antibodies directed to the products of pig B4 GALNT 2. Questions can therefore be asked as to (i) whether the comprehensive structure of the Sda antigen in humans, that is, the underlying sugar structure, is identical to the Sda antigen in pigs, (ii) whether the human anti‐Sda antibody binds ubiquitously to pig cells, but not to human cells, and (iii) what role the Sda++ (also called Cad) antigen is playing in this discrepancy. We review what is known about these antigens and discuss the discrepancies that have been noted above.