Recent investigations into pig antigen and anti-pig antibody expression

Guerard W. Byrne; Christopher G.A. McGregor; Michael E. Breimer

doi:10.1016/j.ijsu.2015.07.724

Recent investigations into pig antigen and anti-pig antibody expression

Guerard W. Byrne, Christopher G.A. McGregor, Michael E. Breimer

Research output: Contribution to journal › Review article › peer-review

57 Scopus citations

Abstract

Genetic engineering of donor pigs to eliminate expression of the dominant xenogeneic antigen galactose α1,3 galactose (Gal) has created a sea change in the immunobiology of xenograft rejection. Antibody mediated xenograft rejection of GGTA-1 α-galactosyltransferase (GTKO) deficient organs is now directed to a combination of non-Gal pig protein and carbohydrate antigens. Glycan analysis of GTKO tissues identified no new neo-antigens but detected high levels of N-acetylneuraminic acid (Neu5Gc) modified glycoproteins and glycolipids. Humans produce anti-Neu5Gc antibody and in very limited clinical studies sometimes show an induced anti-Neu5Gc antibody response after challenge with pig tissue. The pathogenicity of anti-Neu5Gc antibody in xenotransplantation is not clear however as non-human transplant models, critical for modelling anti-Gal immunity, do not produce anti-Neu5Gc antibody. Antibody induced after xenotransplantation in non-human primates is directed to an array of pig endothelial cells proteins and to a glycan produced by the pig B4GALNT2 gene. We anticipate that immune suppression will significantly affect the T-cell dependent and independent specificity of an induced antibody response and that donor pigs deficient in synthesis of multiple xenogeneic glycans will be important to future studies.

Original language	English (US)
Pages (from-to)	223-228
Number of pages	6
Journal	International Journal of Surgery
Volume	23
DOIs	https://doi.org/10.1016/j.ijsu.2015.07.724
State	Published - Nov 1 2015
Externally published	Yes

Bibliographical note

Funding Information:
Funding for this work was provided to Dr. Byrne and McGregor by an Immunobiology of Xenotransplantation cooperative research grant ( AI066310 ) from the National Institute of Allergy and Infectious Disease at the National Institute of Health, by Comprehensive Biomedical Research Centre funds from the National Institute of Health Research, and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Dr. Breimer was supported by governmental grants to the Sahlgrenska University Hospital .

Publisher Copyright:
© 2015 IJS Publishing Group Limited.

Keywords

Antibody
Antigen
Non-Gal
Xenotransplantation

Access

10.1016/j.ijsu.2015.07.724

OpenUrl availability

Full text

Cite this

@article{c8e43c3e07294ae39ff74bfb2dc66f56,

title = "Recent investigations into pig antigen and anti-pig antibody expression",

abstract = "Genetic engineering of donor pigs to eliminate expression of the dominant xenogeneic antigen galactose α1,3 galactose (Gal) has created a sea change in the immunobiology of xenograft rejection. Antibody mediated xenograft rejection of GGTA-1 α-galactosyltransferase (GTKO) deficient organs is now directed to a combination of non-Gal pig protein and carbohydrate antigens. Glycan analysis of GTKO tissues identified no new neo-antigens but detected high levels of N-acetylneuraminic acid (Neu5Gc) modified glycoproteins and glycolipids. Humans produce anti-Neu5Gc antibody and in very limited clinical studies sometimes show an induced anti-Neu5Gc antibody response after challenge with pig tissue. The pathogenicity of anti-Neu5Gc antibody in xenotransplantation is not clear however as non-human transplant models, critical for modelling anti-Gal immunity, do not produce anti-Neu5Gc antibody. Antibody induced after xenotransplantation in non-human primates is directed to an array of pig endothelial cells proteins and to a glycan produced by the pig B4GALNT2 gene. We anticipate that immune suppression will significantly affect the T-cell dependent and independent specificity of an induced antibody response and that donor pigs deficient in synthesis of multiple xenogeneic glycans will be important to future studies.",

keywords = "Antibody, Antigen, Non-Gal, Xenotransplantation",

author = "Byrne, {Guerard W.} and McGregor, {Christopher G.A.} and Breimer, {Michael E.}",

note = "Funding Information: Funding for this work was provided to Dr. Byrne and McGregor by an Immunobiology of Xenotransplantation cooperative research grant ( AI066310 ) from the National Institute of Allergy and Infectious Disease at the National Institute of Health, by Comprehensive Biomedical Research Centre funds from the National Institute of Health Research, and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Dr. Breimer was supported by governmental grants to the Sahlgrenska University Hospital . Publisher Copyright: {\textcopyright} 2015 IJS Publishing Group Limited.",

year = "2015",

month = nov,

day = "1",

doi = "10.1016/j.ijsu.2015.07.724",

language = "English (US)",

volume = "23",

pages = "223--228",

journal = "International Journal of Surgery",

issn = "1743-9191",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Recent investigations into pig antigen and anti-pig antibody expression

AU - Byrne, Guerard W.

AU - McGregor, Christopher G.A.

AU - Breimer, Michael E.

N1 - Funding Information: Funding for this work was provided to Dr. Byrne and McGregor by an Immunobiology of Xenotransplantation cooperative research grant ( AI066310 ) from the National Institute of Allergy and Infectious Disease at the National Institute of Health, by Comprehensive Biomedical Research Centre funds from the National Institute of Health Research, and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Dr. Breimer was supported by governmental grants to the Sahlgrenska University Hospital . Publisher Copyright: © 2015 IJS Publishing Group Limited.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Genetic engineering of donor pigs to eliminate expression of the dominant xenogeneic antigen galactose α1,3 galactose (Gal) has created a sea change in the immunobiology of xenograft rejection. Antibody mediated xenograft rejection of GGTA-1 α-galactosyltransferase (GTKO) deficient organs is now directed to a combination of non-Gal pig protein and carbohydrate antigens. Glycan analysis of GTKO tissues identified no new neo-antigens but detected high levels of N-acetylneuraminic acid (Neu5Gc) modified glycoproteins and glycolipids. Humans produce anti-Neu5Gc antibody and in very limited clinical studies sometimes show an induced anti-Neu5Gc antibody response after challenge with pig tissue. The pathogenicity of anti-Neu5Gc antibody in xenotransplantation is not clear however as non-human transplant models, critical for modelling anti-Gal immunity, do not produce anti-Neu5Gc antibody. Antibody induced after xenotransplantation in non-human primates is directed to an array of pig endothelial cells proteins and to a glycan produced by the pig B4GALNT2 gene. We anticipate that immune suppression will significantly affect the T-cell dependent and independent specificity of an induced antibody response and that donor pigs deficient in synthesis of multiple xenogeneic glycans will be important to future studies.

AB - Genetic engineering of donor pigs to eliminate expression of the dominant xenogeneic antigen galactose α1,3 galactose (Gal) has created a sea change in the immunobiology of xenograft rejection. Antibody mediated xenograft rejection of GGTA-1 α-galactosyltransferase (GTKO) deficient organs is now directed to a combination of non-Gal pig protein and carbohydrate antigens. Glycan analysis of GTKO tissues identified no new neo-antigens but detected high levels of N-acetylneuraminic acid (Neu5Gc) modified glycoproteins and glycolipids. Humans produce anti-Neu5Gc antibody and in very limited clinical studies sometimes show an induced anti-Neu5Gc antibody response after challenge with pig tissue. The pathogenicity of anti-Neu5Gc antibody in xenotransplantation is not clear however as non-human transplant models, critical for modelling anti-Gal immunity, do not produce anti-Neu5Gc antibody. Antibody induced after xenotransplantation in non-human primates is directed to an array of pig endothelial cells proteins and to a glycan produced by the pig B4GALNT2 gene. We anticipate that immune suppression will significantly affect the T-cell dependent and independent specificity of an induced antibody response and that donor pigs deficient in synthesis of multiple xenogeneic glycans will be important to future studies.

KW - Antibody

KW - Antigen

KW - Non-Gal

KW - Xenotransplantation

UR - http://www.scopus.com/inward/record.url?scp=84951573769&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84951573769&partnerID=8YFLogxK

U2 - 10.1016/j.ijsu.2015.07.724

DO - 10.1016/j.ijsu.2015.07.724

M3 - Review article

C2 - 26306769

AN - SCOPUS:84951573769

SN - 1743-9191

VL - 23

SP - 223

EP - 228

JO - International Journal of Surgery

JF - International Journal of Surgery

ER -

Recent investigations into pig antigen and anti-pig antibody expression

Abstract

Bibliographical note

Keywords

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this