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The Structural Complexity and Animal Tissue Distribution of N-Glycolylneuraminic Acid (Neu5Gc)-Terminated Glycans. Implications for Their Immunogenicity in Clinical Xenografting

Artikel i vetenskaplig tidskrift
Författare Michael Breimer
Jan Holgersson
Publicerad i Frontiers in Molecular Biosciences
Volym 6
Publiceringsår 2019
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för kirurgi
Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin
Språk en
Länkar dx.doi.org/10.3389/fmolb.2019.00057
Ämnesord N-glycolylneuraminic acid, xenograft, bioprosthetic heart valve, carbohydrate antigen, anti-carbohydrate antibodies, carbohydrate epitope, nonhuman sialic-acid, protein-carbohydrate interactions, hanganutziu-deicher antigens, human xeno-autoantibodies, ex-vivo, connection, alpha-gal, immune-response, pig-heart, heterophile, hanganutziu, anti-neu5gc antibodies, Biochemistry & Molecular Biology, hauer r, 1968, hoppe-seylers zeitschrift fur physiologische chemie, v349, p645, HAUER R, 1991, Glycobiology, V1, P449
Ämneskategorier Cell- och molekylärbiologi

Sammanfattning

N-Glycolylneuraminic acid (Neu5Gc)-terminated glycans are present in all animal cells/tissues that are already used in the clinic such as bioprosthetic heart valves (BHV) as well as in those that potentially will be xenografted in the future to overcome end stage cell/organ failure. Humans, as a species lack this antigen determinant and can react with an immune response after exposure to Neu5Gc present in these products/cells/tissues. Genetically engineered source animals lacking Neu5Gc has been generated and so has animals that in addition lack the major alpha Gal xenoantigen. The use of cells/tissues/organs from such animals may improve the long-term performance of BHV and allow future xenografting. This review summarizes the present knowledge regarding structural complexity and tissue distribution of Neu5Gc on glycans of cells/tissue/organs already used in the clinic or intended for treatment of end stage organ failure by xenografting. In addition, we briefly discuss the role of anti-Neu5Gc antibodies in the xenorejection process and how knowledge about Neu5Gc structural complexity can be used to design novel diagnostics for anti-Neu5Gc antibody detection.

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