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B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158069/ https://www.ncbi.nlm.nih.gov/pubmed/29604134 http://dx.doi.org/10.1111/xen.12394 |
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author | Byrne, Guerard Ahmad‐Villiers, Saadullah Du, Zeji McGregor, Christopher |
author_facet | Byrne, Guerard Ahmad‐Villiers, Saadullah Du, Zeji McGregor, Christopher |
author_sort | Byrne, Guerard |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6158069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61580692018-10-15 B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen Byrne, Guerard Ahmad‐Villiers, Saadullah Du, Zeji McGregor, Christopher Xenotransplantation Review Articles 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. John Wiley and Sons Inc. 2018-03-31 2018 /pmc/articles/PMC6158069/ /pubmed/29604134 http://dx.doi.org/10.1111/xen.12394 Text en © 2018 The Authors. Xenotransplantation Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Articles Byrne, Guerard Ahmad‐Villiers, Saadullah Du, Zeji McGregor, Christopher B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen |
title | B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen |
title_full | B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen |
title_fullStr | B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen |
title_full_unstemmed | B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen |
title_short | B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen |
title_sort | b4galnt2 and xenotransplantation: a newly appreciated xenogeneic antigen |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158069/ https://www.ncbi.nlm.nih.gov/pubmed/29604134 http://dx.doi.org/10.1111/xen.12394 |
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