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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

Journal article
Authors Michael Breimer
Jan Holgersson
Published in Frontiers in Molecular Biosciences
Volume 6
ISSN 2296-889X
Publication year 2019
Published at Institute of Clinical Sciences, Department of Surgery
Institute of Biomedicine
Language en
Links dx.doi.org/10.3389/fmolb.2019.00057
Keywords 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
Subject categories Cell and Molecular Biology

Abstract

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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