Shenzhen Xenotransplantation Medical Engineering Research and Development Center, Institute of Translational Medicine, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen University School of Medicine, Shenzhen, Guangdong, China.
Xenotransplantation Program, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA.
Xenotransplantation. 2018 Mar;25(2):e12386. doi: 10.1111/xen.12386. Epub 2018 Feb 11.
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 (GalNAc) could serve as a potential xenoantigen. GalNAc is the immunodominant glycan of the Sda antigen. Recently, knockout of β1,4-N-acetylgalactosaminyltransferase 2 (β1,4GalNAcT-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 GalNAc on the Sda antigen, which is catalyzed by the enzyme, β1,4GalNAcT-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 B4GALNT2. 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.
抗体介导的排斥反应是异种移植临床应用的障碍，而异种抗原在这一过程中起着重要作用。早期的研究表明，N-乙酰-D-半乳糖胺（GalNAc）可以作为一种潜在的异种抗原。GalNAc 是 Sda 抗原的免疫优势聚糖。最近，敲除猪的β1,4-N-乙酰半乳糖胺基转移酶 2（β1,4GalNAcT-II）导致人血清抗体与猪细胞结合减少。据信，这是由于该酶β1,4GalNAcT-II 催化的 Sda 抗原上 GalNAc 的消除所致。然而，对人类血型抗原的研究表明，只有一小部分（1%-2%）的人表达针对 Sda 抗原的抗 Sda 抗体，而大多数人似乎具有针对猪 B4GALNT2 产物的抗体。因此，可以提出以下问题：（i）人类 Sda 抗原的综合结构，即潜在的糖结构，是否与猪的 Sda 抗原相同；（ii）人类抗 Sda 抗体是否广泛结合猪细胞而不结合人细胞；（iii）Sda（也称为 Cad）抗原在这种差异中起什么作用。我们回顾了这些抗原的已知情况，并讨论了上述差异。
