Potential deleterious role of anti‐Neu5Gc antibodies in xenotransplantation
Abstract
Human beings do not synthesize the glycolyl form of the sialic acid (Neu5Gc) and only express the acetylated form of the sugar, whereas a diet‐based intake of Neu5Gc provokes a natural immunization and production of anti‐Neu5Gc antibodies in human serum. However, Neu5Gc is expressed on mammal glycoproteins and glycolipids in most organs and cells. We review here the relevance of Neu5Gc and anti‐Neu5Gc antibodies in the context of xenotransplantation and the use of animal‐derived molecules and products, as well as the possible consequences of a long‐term exposure to anti‐Neu5Gc antibodies in recipients of xenografts. In addition, the importance of an accurate estimation of the anti‐Neu5Gc response following xenotransplantation and the future contribution of knockout animals mimicking the human situation are also assessed.
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Neu5Gc expression level is a tissue-dependent issue.
“Neu5Gc expression level is a tissue-dependent issue.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [137]
The findings of non-human primate kidney transplantation could be ascribed to a lower presence of preformed antibodies and IgM/IgG titer alongside inferiority in expressing these epitopes and their affinity to antibodies.
“The findings could be ascribed to a lower presence of preformed antibodies and IgM/IgG titer alongside inferiority in expressing these epitopes and their affinity to antibodies [137].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [137]
Neu5Gc antigen-antibody interaction is less destructive than the same for α-gals.
“Although a large body of data indicates the critical role of Neu5Gc antigen-antibody interactions in mediating chronic inflammatory conditions such as cancer and atherosclerosis [127, 138–141], Neu5Gc antigen-antibody interaction is less destructive than the same for α-gals [137].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [137]
Despite detrimental effects of Neu5Gc epitopes on immunogenicity of decellularized heart valves and dermal grafts, neurons are privileged of Neu5Gc expression.
“Despite the detrimental effects of these epitopes on the immunogenicity of decellularized heart valves [137, 138, 142], and dermal grafts, neurons are privileged of Neu5Gc expression [131, 137, 143].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [137]
Deleterious mutations during evolution inactivated the CMAH gene in human and new world monkeys and made their cells exclusively express Neu5Ac, and produce antibodies against Neu5GC.
“Deleterious mutations during evolution inactivated the CMAH gene in human and new world monkeys and made their cells exclusively express the acetylated form of sialic acid, Neu5Ac, and produce antibodies against the glycolyl form, Neu5GC [136, 137].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [137]
Cites
Lutz, A. J., Li, P., Estrada, J. L., Sidner, R. A., Chihara, R. K., Downey, S. M., Burlak, C., Wang, Z., Reyes, L. M., Ivary, B., et al. (2013) · Xenotransplantation · doi:10.1111/xen.12019 · Cited by 294 · see citing works
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Varki, A. (2017) · Glycobiology · doi:10.1093/glycob/cww086 · Cited by 2,635 · see citing works
Kasravi, M., Ahmadi, A., Babajani, A., Mazloomnejad, R., Hatamnejad, M. R., Shariatzadeh, S., Bahrami, S., & Niknejad, H. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00348-z · Cited by 316 · see citing works
The Possible Role of Anti-Neu5Gc as an Obstacle in Xenotransplantation
Tector, A. J., Mosser, M., Tector, M., & Bach, J.-M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00622 · Cited by 60 · see citing works
Morticelli, L., Magdei, M., Tschalaki, N., Petersen, B., Haverich, A., & Hilfiker, A. (2021) · Xenotransplantation · doi:10.1111/xen.12705 · Cited by 7 · see citing works
- Authors
- Salama, A., Evanno, G., Harb, J., & Soulillou, J.
- Affiliations
- Inserm (FR)
- Corresponding author
- Soulillou, Jean‐Paul
- Venue
- Xenotransplantation
- Publisher
- Wiley
- Published
- 2014-10-13
- Volume
- 22
- Issue
- 2
- Pages
- 85-94
- ISSN
- 0908-665X (ISSN-L)
- 1399-3089
- OpenAlex
- W2091505613
- Cited by
- 81
- References
- 1
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 5 · 2022: 8 · 2021: 6 · 2020: 9 · 2019: 11 · 2018: 7 · 2017: 11 · 2016: 9 · 2015: 7
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Xenotransplantation (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- European Commission (603049)
- Société d'Accélération du Transfert de Technologies Ouest Valorisation
- Topics
- Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- anti-Neu5Gc antibodies, N-glycolylneuraminic acid, xenograft rejection, sialic acid, natural immunization, animal products, xenotransplantation safety, knockout animals, glycosylation
- MeSH terms
- Animals, Animals, Laboratory, Antibodies, Heterophile, Humans, Immunity, Innate, Neuraminic Acids, Primates, Transplantation, Heterologous, Antigens, Heterophile, Organ Transplantation, Models, Animal, Sus scrofa
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