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 αGal 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.
Highlights
Products isolated from animal tissues have been used in clinical medicine for a long time as exemplified by porcine insulin introduced in the 1920’s and bioprosthetic heart valves (BHV) in 1965 (Binet et al, 1965)
This review summarizes the present knowledge regarding the structural complexity and distribution of Neu5Gc on glycans of BHV as well as cells/organs intended for treatment of end stage organ failure by xenografting
In 1986, Mukuria et al described an enzyme-linked immunosorbent assay (ELISA) for detection of Hanganutiziu and Deicher (HD) antibodies using flat-bottomed 96-well plates coated with purified Neu5GcLacCer (Mukuria et al, 1986b)
Summary
Products isolated from animal tissues have been used in clinical medicine for a long time as exemplified by porcine insulin introduced in the 1920’s and bioprosthetic heart valves (BHV) in 1965 (Binet et al, 1965). N-glycans released from pig kidney cell membrane glycoproteins revealed several novel Neu5Gc-terminated saccharides with up to 14 monosaccharide units present in complex branched structures (Kim et al, 2008). These studies were performed by a combination of HPLC separation of released saccharides followed by MALDI-TOF mass spectrometry. To detect all Neu5Gc antibodies and not to miss a part of the anti-Neu5Gc repertoire, it is important that the assays used are based on a broad repertoire of Neu5Gc-terminated glycans linked to different core chains and with different linkage configurations between Neu5Gc and the penultimate sugar residue (Padler-Karavani et al, 2008). The knowledge regarding the immune response to Neu5Gc glycans in humans exposed to animal tissues is limited as is the knowledge regarding the potential clinical significance of anti-Neu5Gc antibodies in allo- and xenograft rejection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
