Profiling natural serum antibodies of non-human primates with a carbohydrate antigen microarray

Yoshihide Nanno; Eric Sterner; Jeffrey C. Gildersleeve; Bernhard J. Hering; Christopher Burlak

doi:10.1111/xen.12567

Profiling natural serum antibodies of non-human primates with a carbohydrate antigen microarray

Yoshihide Nanno, Eric Sterner, Jeffrey C. Gildersleeve, Bernhard J. Hering, Christopher Burlak

Surgery

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Abstract

Background: Engineering of α-Galactosyltransferase gene-knockout pigs circumvented hyperacute rejection of pig organs after xenotransplantation in non-human primates. Overcoming this hurdle revealed the importance of non-α-Gal carbohydrate antigens in the immunobiology of acute humoral xenograft rejection. Methods: This study analyzed serum from seven naïve cynomolgus monkeys (blood type O/B/AB = 3/2/2) for the intensity of natural IgM and IgG signals using carbohydrate antigen microarray, which included historically reported α-Gal and non-α-Gal carbohydrate antigens with various modifications. Results: The median (range) of IgM and IgG signals were 12.71 (7.23-16.38) and 9.05 (7.23-15.90), respectively. The highest IgM and IgG signals with narrowest distribution were from mono- and disaccharides, followed by modified structures. Natural anti-α-Gal antibody signals were medium to high in IgM (11.2-15.9) and medium in IgG (8.5-11.6) spectra, and was highest with Lac core structure (Galα1-3Galβ1-4Glc, iGb3) and lowest with LacNAc core structure (Galα1-3Galβ1-4GlcNAc). Similar signal intensities (up to 15.8 in IgM and up to 11.8 in IgG) were observed for historically detected natural non-α-Gal antigens, which included Tn antigen, T antigen, GM2 glycolipid, and Sd^a antigen. The hierarchical clustering analysis revealed the presence of clusters of anti-A antibodies and was capable of distinguishing between the blood group B and AB non-human primates. Conclusions: The results presented here provide the most comprehensive evaluation of natural antibodies present in cynomolgus monkeys.

Original language	English (US)
Article number	e12567
Journal	Xenotransplantation
Volume	27
Issue number	2
DOIs	https://doi.org/10.1111/xen.12567
State	Published - Mar 1 2020

Bibliographical note

Funding Information:
We thank the Consortium for Functional Glycomics (GM62116; The Scripps Research Institute), Professors Tom Tolbert (University of Kansas), Lai-Xi Wang (University of Maryland), Xuefei Huang (Michigan State University), Todd Lowary (University of Alberta), and Dr Joseph Barchi (National Cancer Institute) for contributing glycans for the array. This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. We gratefully acknowledge the University of Minnesota's Preclinical Research Center, directed by Dr Melanie Graham, that conducted studies in non-human primates from which retention samples were obtained.

Funding Information:
We thank the Consortium for Functional Glycomics (GM62116; The Scripps Research Institute), Professors Tom Tolbert (University of Kansas), Lai‐Xi Wang (University of Maryland), Xuefei Huang (Michigan State University), Todd Lowary (University of Alberta), and Dr Joseph Barchi (National Cancer Institute) for contributing glycans for the array. This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. We gratefully acknowledge the University of Minnesota's Preclinical Research Center, directed by Dr Melanie Graham, that conducted studies in non‐human primates from which retention samples were obtained.

Publisher Copyright:
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords

carbohydrate antigen microarray
natural serum antibodies
non-human primates
xenotransplantation

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10.1111/xen.12567

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title = "Profiling natural serum antibodies of non-human primates with a carbohydrate antigen microarray",

abstract = "Background: Engineering of α-Galactosyltransferase gene-knockout pigs circumvented hyperacute rejection of pig organs after xenotransplantation in non-human primates. Overcoming this hurdle revealed the importance of non-α-Gal carbohydrate antigens in the immunobiology of acute humoral xenograft rejection. Methods: This study analyzed serum from seven na{\"i}ve cynomolgus monkeys (blood type O/B/AB = 3/2/2) for the intensity of natural IgM and IgG signals using carbohydrate antigen microarray, which included historically reported α-Gal and non-α-Gal carbohydrate antigens with various modifications. Results: The median (range) of IgM and IgG signals were 12.71 (7.23-16.38) and 9.05 (7.23-15.90), respectively. The highest IgM and IgG signals with narrowest distribution were from mono- and disaccharides, followed by modified structures. Natural anti-α-Gal antibody signals were medium to high in IgM (11.2-15.9) and medium in IgG (8.5-11.6) spectra, and was highest with Lac core structure (Galα1-3Galβ1-4Glc, iGb3) and lowest with LacNAc core structure (Galα1-3Galβ1-4GlcNAc). Similar signal intensities (up to 15.8 in IgM and up to 11.8 in IgG) were observed for historically detected natural non-α-Gal antigens, which included Tn antigen, T antigen, GM2 glycolipid, and Sda antigen. The hierarchical clustering analysis revealed the presence of clusters of anti-A antibodies and was capable of distinguishing between the blood group B and AB non-human primates. Conclusions: The results presented here provide the most comprehensive evaluation of natural antibodies present in cynomolgus monkeys.",

keywords = "carbohydrate antigen microarray, natural serum antibodies, non-human primates, xenotransplantation",

author = "Yoshihide Nanno and Eric Sterner and Gildersleeve, {Jeffrey C.} and Hering, {Bernhard J.} and Christopher Burlak",

note = "Funding Information: We thank the Consortium for Functional Glycomics (GM62116; The Scripps Research Institute), Professors Tom Tolbert (University of Kansas), Lai-Xi Wang (University of Maryland), Xuefei Huang (Michigan State University), Todd Lowary (University of Alberta), and Dr Joseph Barchi (National Cancer Institute) for contributing glycans for the array. This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. We gratefully acknowledge the University of Minnesota's Preclinical Research Center, directed by Dr Melanie Graham, that conducted studies in non-human primates from which retention samples were obtained. Funding Information: We thank the Consortium for Functional Glycomics (GM62116; The Scripps Research Institute), Professors Tom Tolbert (University of Kansas), Lai‐Xi Wang (University of Maryland), Xuefei Huang (Michigan State University), Todd Lowary (University of Alberta), and Dr Joseph Barchi (National Cancer Institute) for contributing glycans for the array. This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. We gratefully acknowledge the University of Minnesota's Preclinical Research Center, directed by Dr Melanie Graham, that conducted studies in non‐human primates from which retention samples were obtained. Publisher Copyright: {\textcopyright} 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",

year = "2020",

month = mar,

day = "1",

doi = "10.1111/xen.12567",

language = "English (US)",

volume = "27",

journal = "Xenotransplantation",

issn = "0908-665X",

publisher = "Wiley-Blackwell",

number = "2",

}

TY - JOUR

T1 - Profiling natural serum antibodies of non-human primates with a carbohydrate antigen microarray

AU - Nanno, Yoshihide

AU - Sterner, Eric

AU - Gildersleeve, Jeffrey C.

AU - Hering, Bernhard J.

AU - Burlak, Christopher

N1 - Funding Information: We thank the Consortium for Functional Glycomics (GM62116; The Scripps Research Institute), Professors Tom Tolbert (University of Kansas), Lai-Xi Wang (University of Maryland), Xuefei Huang (Michigan State University), Todd Lowary (University of Alberta), and Dr Joseph Barchi (National Cancer Institute) for contributing glycans for the array. This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. We gratefully acknowledge the University of Minnesota's Preclinical Research Center, directed by Dr Melanie Graham, that conducted studies in non-human primates from which retention samples were obtained. Funding Information: We thank the Consortium for Functional Glycomics (GM62116; The Scripps Research Institute), Professors Tom Tolbert (University of Kansas), Lai‐Xi Wang (University of Maryland), Xuefei Huang (Michigan State University), Todd Lowary (University of Alberta), and Dr Joseph Barchi (National Cancer Institute) for contributing glycans for the array. This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. We gratefully acknowledge the University of Minnesota's Preclinical Research Center, directed by Dr Melanie Graham, that conducted studies in non‐human primates from which retention samples were obtained. Publisher Copyright: © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2020/3/1

Y1 - 2020/3/1

N2 - Background: Engineering of α-Galactosyltransferase gene-knockout pigs circumvented hyperacute rejection of pig organs after xenotransplantation in non-human primates. Overcoming this hurdle revealed the importance of non-α-Gal carbohydrate antigens in the immunobiology of acute humoral xenograft rejection. Methods: This study analyzed serum from seven naïve cynomolgus monkeys (blood type O/B/AB = 3/2/2) for the intensity of natural IgM and IgG signals using carbohydrate antigen microarray, which included historically reported α-Gal and non-α-Gal carbohydrate antigens with various modifications. Results: The median (range) of IgM and IgG signals were 12.71 (7.23-16.38) and 9.05 (7.23-15.90), respectively. The highest IgM and IgG signals with narrowest distribution were from mono- and disaccharides, followed by modified structures. Natural anti-α-Gal antibody signals were medium to high in IgM (11.2-15.9) and medium in IgG (8.5-11.6) spectra, and was highest with Lac core structure (Galα1-3Galβ1-4Glc, iGb3) and lowest with LacNAc core structure (Galα1-3Galβ1-4GlcNAc). Similar signal intensities (up to 15.8 in IgM and up to 11.8 in IgG) were observed for historically detected natural non-α-Gal antigens, which included Tn antigen, T antigen, GM2 glycolipid, and Sda antigen. The hierarchical clustering analysis revealed the presence of clusters of anti-A antibodies and was capable of distinguishing between the blood group B and AB non-human primates. Conclusions: The results presented here provide the most comprehensive evaluation of natural antibodies present in cynomolgus monkeys.

AB - Background: Engineering of α-Galactosyltransferase gene-knockout pigs circumvented hyperacute rejection of pig organs after xenotransplantation in non-human primates. Overcoming this hurdle revealed the importance of non-α-Gal carbohydrate antigens in the immunobiology of acute humoral xenograft rejection. Methods: This study analyzed serum from seven naïve cynomolgus monkeys (blood type O/B/AB = 3/2/2) for the intensity of natural IgM and IgG signals using carbohydrate antigen microarray, which included historically reported α-Gal and non-α-Gal carbohydrate antigens with various modifications. Results: The median (range) of IgM and IgG signals were 12.71 (7.23-16.38) and 9.05 (7.23-15.90), respectively. The highest IgM and IgG signals with narrowest distribution were from mono- and disaccharides, followed by modified structures. Natural anti-α-Gal antibody signals were medium to high in IgM (11.2-15.9) and medium in IgG (8.5-11.6) spectra, and was highest with Lac core structure (Galα1-3Galβ1-4Glc, iGb3) and lowest with LacNAc core structure (Galα1-3Galβ1-4GlcNAc). Similar signal intensities (up to 15.8 in IgM and up to 11.8 in IgG) were observed for historically detected natural non-α-Gal antigens, which included Tn antigen, T antigen, GM2 glycolipid, and Sda antigen. The hierarchical clustering analysis revealed the presence of clusters of anti-A antibodies and was capable of distinguishing between the blood group B and AB non-human primates. Conclusions: The results presented here provide the most comprehensive evaluation of natural antibodies present in cynomolgus monkeys.

KW - carbohydrate antigen microarray

KW - natural serum antibodies

KW - non-human primates

KW - xenotransplantation

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DO - 10.1111/xen.12567

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AN - SCOPUS:85075474799

SN - 0908-665X

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JO - Xenotransplantation

JF - Xenotransplantation

IS - 2

M1 - e12567

ER -

Profiling natural serum antibodies of non-human primates with a carbohydrate antigen microarray

Abstract

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