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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...

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Autores principales: Byrne, Guerard, Ahmad‐Villiers, Saadullah, Du, Zeji, McGregor, Christopher
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
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.
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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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