Carbohydrate antigen microarray analysis of serum IgG and IgM antibodies before and after adult porcine islet xenotransplantation in cynomolgus macaques.

Understanding the anti-carbohydrate antibody response toward epitopes expressed on porcine cells, tissues, and organs is critical to advancing xenotransplantation toward clinical application. In this study, we determined IgM and IgG antibody specificities and relative concentrations in five cynomolg...

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Autores principales:	Yoshihide Nanno, Eric Sterner, Jeffrey C Gildersleeve, Bernhard J Hering, Christopher Burlak
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/86d9b45ea8f240bb984d7873bf73219c
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spelling	oai:doaj.org-article:86d9b45ea8f240bb984d7873bf73219c2021-12-02T20:10:27ZCarbohydrate antigen microarray analysis of serum IgG and IgM antibodies before and after adult porcine islet xenotransplantation in cynomolgus macaques.1932-620310.1371/journal.pone.0253029https://doaj.org/article/86d9b45ea8f240bb984d7873bf73219c2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253029https://doaj.org/toc/1932-6203Understanding the anti-carbohydrate antibody response toward epitopes expressed on porcine cells, tissues, and organs is critical to advancing xenotransplantation toward clinical application. In this study, we determined IgM and IgG antibody specificities and relative concentrations in five cynomolgus monkeys at baseline and at intervals following intraportal xenotransplantation of adult porcine islets. This study utilized a carbohydrate antigen microarray that comprised more than 400 glycoconjugates, including historically reported α-Gal and non-α-Gal carbohydrate antigens with various modifications. The elicited anti-carbohydrate antibody responses were predominantly IgM compared to IgG in 4 out of 5 monkeys. Patterns of elicited antibody responses greater than 1.5 difference (log2 base units; 2.8-fold on a linear scale) from pre-serum to post-serum sampling specific for carbohydrate antigens were heterogeneous and recipient-specific. Increases in the elicited antibody response to α-Gal, Sda, GM2 antigens, or Lexis X antigen were found in individual monkeys. The novel carbohydrate structures Galβ1-4GlcNAcβ1-3Galβ1 and N-linked glycans with Manα1-6(GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ structure were common targets of elicited IgM antibodies. These results provide important insights into the carbohydrate epitopes that elicit antibodies following pig-to-monkey islet xenotransplantation and reveal possible targets for gene editing.Yoshihide NannoEric SternerJeffrey C GildersleeveBernhard J HeringChristopher BurlakPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0253029 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoshihide Nanno Eric Sterner Jeffrey C Gildersleeve Bernhard J Hering Christopher Burlak Carbohydrate antigen microarray analysis of serum IgG and IgM antibodies before and after adult porcine islet xenotransplantation in cynomolgus macaques.
description	Understanding the anti-carbohydrate antibody response toward epitopes expressed on porcine cells, tissues, and organs is critical to advancing xenotransplantation toward clinical application. In this study, we determined IgM and IgG antibody specificities and relative concentrations in five cynomolgus monkeys at baseline and at intervals following intraportal xenotransplantation of adult porcine islets. This study utilized a carbohydrate antigen microarray that comprised more than 400 glycoconjugates, including historically reported α-Gal and non-α-Gal carbohydrate antigens with various modifications. The elicited anti-carbohydrate antibody responses were predominantly IgM compared to IgG in 4 out of 5 monkeys. Patterns of elicited antibody responses greater than 1.5 difference (log2 base units; 2.8-fold on a linear scale) from pre-serum to post-serum sampling specific for carbohydrate antigens were heterogeneous and recipient-specific. Increases in the elicited antibody response to α-Gal, Sda, GM2 antigens, or Lexis X antigen were found in individual monkeys. The novel carbohydrate structures Galβ1-4GlcNAcβ1-3Galβ1 and N-linked glycans with Manα1-6(GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ structure were common targets of elicited IgM antibodies. These results provide important insights into the carbohydrate epitopes that elicit antibodies following pig-to-monkey islet xenotransplantation and reveal possible targets for gene editing.
format	article
author	Yoshihide Nanno Eric Sterner Jeffrey C Gildersleeve Bernhard J Hering Christopher Burlak
author_facet	Yoshihide Nanno Eric Sterner Jeffrey C Gildersleeve Bernhard J Hering Christopher Burlak
author_sort	Yoshihide Nanno
title	Carbohydrate antigen microarray analysis of serum IgG and IgM antibodies before and after adult porcine islet xenotransplantation in cynomolgus macaques.
title_short	Carbohydrate antigen microarray analysis of serum IgG and IgM antibodies before and after adult porcine islet xenotransplantation in cynomolgus macaques.
title_full	Carbohydrate antigen microarray analysis of serum IgG and IgM antibodies before and after adult porcine islet xenotransplantation in cynomolgus macaques.
title_fullStr	Carbohydrate antigen microarray analysis of serum IgG and IgM antibodies before and after adult porcine islet xenotransplantation in cynomolgus macaques.
title_full_unstemmed	Carbohydrate antigen microarray analysis of serum IgG and IgM antibodies before and after adult porcine islet xenotransplantation in cynomolgus macaques.
title_sort	carbohydrate antigen microarray analysis of serum igg and igm antibodies before and after adult porcine islet xenotransplantation in cynomolgus macaques.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/86d9b45ea8f240bb984d7873bf73219c
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_version_	1718375011090169856

Carbohydrate antigen microarray analysis of serum IgG and IgM antibodies before and after adult porcine islet xenotransplantation in cynomolgus macaques.

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