UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen

Byrne, G; Ahmad-Villiers, S; Du, Z; McGregor, C; (2018) B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen. Xenotransplantation , 25 (5) , Article e12394. 10.1111/xen.12394. Green open access

[thumbnail of Byrne_B4GALNT2 and xenotransplantation. A newly appreciated xenogeneic antigen_VoR.pdf]
Preview
Text
Byrne_B4GALNT2 and xenotransplantation. A newly appreciated xenogeneic antigen_VoR.pdf

Download (846kB) | Preview

Abstract

Analysis of non-Gal antibody induced after pig-to-baboon cardiac xenotransplantation identified the glycan produced by porcine beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2) as an immunogenic xenotransplantation antigen. The porcine B4GALNT2 enzyme is homologous to the human enzyme, which synthesizes the human SDa blood group antigen. Most humans produce low levels of anti-SDa IgM which polyagglutinates red blood cells from rare individuals with high levels of SDa expression. The SDa glycan is also present on GM2 gangliosides. Clinical GM2 vaccination studies for melanoma patients suggest that a human antibody response to SDa can be induced. Expression of porcine B4GALNT2 in human HEK293 cells results in increased binding of anti-SDa antibody and increased binding of Dolichos biflorus agglutinin (DBA), a lectin commonly used to detect SDa. In pigs, B4GALNT2 is expressed by vascular endothelial cells and endothelial cells from a wide variety of pig backgrounds stain with DBA, suggesting that porcine vascular expression of B4GALNT2 is not polymorphic. Mutations in B4GALNT2 have been engineered in mice and pigs. In both species, the B4GALNT2-KO animals are apparently normal and no longer show evidence of SDa antigen expression. Pig tissues with a mutation in B4GALNT2, added to a background of alpha-1,3-galactosyltransferase deficient (GGTA1-KO) and cytidine monophosphate-N-acetylneuraminic acid hydroxylase deficient (CMAH-KO), show reduced antibody binding, confirming the presence of B4GALNT2-dependent antibodies in both humans and non-human primates. Preclinical xenotransplantation using B4GALNT2-deficient donors has recently been reported. Elimination of this source of immunogenic pig antigen should minimize acute injury by preformed anti-pig antibody and eliminate an induced clinical immune response to this newly appreciated xenotransplantation antigen.

Type: Article
Title: B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen
Location: Denmark
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/xen.12394
Publisher version: https://doi.org/10.1111/xen.12394
Language: English
Additional information: © 2018 The Authors. Xenotransplantation Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Antibody-mediated rejection, beta-1,4-N-acetyl-galactosaminyltransferase 2, cardiac xenotransplantation, genetic modification, xenotransplantation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/10050149
Downloads since deposit
93Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item