Characterization of immunogenic Neu5Gc in bioprosthetic heart valves

Autor: Hai Yu, Xi Chen, Emanuele Cozzi, Shani Leviatan Ben-Arye, Eliran Moshe Reuven, Jean-Paul Soulillou, Cristina Costa, Michael E. Breimer, Rafael Mañez, Imen Fellah-Hebia, Jean Christian Roussel, Vered Padler-Karavani, Manuel Galiñanes, Tal Marshanski, Thierry Le Tourneau
Přispěvatelé: Department of Cell Research and Immunology, Tel Aviv University (TAU), Department of Surgery [Gothenburg, Sweden] (Institute of Clinical Sciences), Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Chemistry [Univ California Davis] (Chemistry - UC Davis), University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Département de chirurgie thoracique et cardiovasculaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Infectious Diseases and Transplantation Division [Barcelona, Spain], L’Hospitalet de Llobregat [Barcelona, Spain]-Bellvitge Biomedical Research Institute IDIBELL [Barcelona, Spain], Department of Cardiac Surgery & Reparative Therapy of the Heart [Barcelona, Spain], Vall d'Hebron University Hospital [Barcelona]-Vall d’Hebron Research Institute (VHIR), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Transplant Immunology Unit [Padua, Italy], Padua General Hospital [Padua, Italy], This work was supported in part by a grant from the Israeli National Nanotechnology Initiative and Helmsley Charitable Trust for a Focal Technology Area on Nanomedicines for Personalized Theranostics. National Institutes of Health grant R01GM076360, and Governmental grants to the Sahlgrenska University Hospital., European Project, Tel Aviv University [Tel Aviv], Department of Chemistry [Davis, CA, USA], University of California-University of California, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Le Bihan, Sylvie, The European Commission's 7th Framework Programme Marie-Curie grant PIIF-GA-2012-327726 - INCOMING, the European Commission's 7th Framework Programme FP7-Health-2013-INNOVATION-1 - INCOMING
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Xenotransplantation
Xenotransplantation, 2016, 23 (5), pp.381-392. ⟨10.1111/xen.12260⟩
Recercat. Dipósit de la Recerca de Catalunya
instname
Xenotransplantation, Wiley, 2016, 23 (5), pp.381-392. ⟨10.1111/xen.12260⟩
Dipòsit Digital de la UB
Universidad de Barcelona
Xenotransplantation, vol 23, iss 5
ISSN: 0908-665X
1399-3089
DOI: 10.1111/xen.12260⟩
Popis: International audience; BACKGROUND: The two common sialic acids (Sias) in mammals are N-acetylneuraminic acid (Neu5Ac) and its hydroxylated form N-glycolylneuraminic acid (Neu5Gc). Unlike most mammals, humans cannot synthesize Neu5Gc that is considered foreign and recognized by circulating antibodies. Thus, Neu5Gc is a potential xenogenic carbohydrate antigen in bioprosthetic heart valves (BHV) that tend to deteriorate in time within human patients.METHODS: We investigated Neu5Gc expression in non-engineered animal-derived cardiac tissues and in clinically used commercial BHV, and evaluated Neu5Gc immunogenicity on BHV through recognition by human anti-Neu5Gc IgG.RESULTS: Neu5Gc was detected by immunohistochemistry in porcine aortic valves and in porcine and bovine pericardium. Qualitative analysis of Sia linkages revealed Siaα2-3>Siaα2-6 on porcine/bovine pericardium while the opposite in porcine aortic/pulmonary valve cusps. Similarly, six commercial BHV containing either porcine aortic valve or porcine/bovine/equine pericardium revealed Siaα2-3>Siaα2-6 expression. Quantitative analysis of Sia by HPLC showed porcine/bovine pericardium express 4-fold higher Neu5Gc levels compared to the porcine aortic/pulmonary valves, with Neu5Ac at 6-fold over Neu5Gc. Likewise, Neu5Gc was expressed on commercial BHV (186.3±16.9 pmol Sia/μg protein), with Neu5Ac at 8-fold over Neu5Gc. Affinity-purified human anti-Neu5Gc IgG showing high specificity toward Neu5Gc-glycans (with no binding to Neu5Ac-glycans) on a glycan microarray, strongly bound to all tested commercial BHV, demonstrating Neu5Gc immune recognition in cardiac xenografts.CONCLUSIONS: We conclusively demonstrated Neu5Gc expression in native cardiac tissues, as well as in six commercial BHV. These Neu5Gc xeno-antigens were recognized by human anti-Neu5Gc IgG, supporting their immunogenicity. Altogether, these findings suggest BHV-Neu5Gc/anti-Neu5Gc may play a role in valve deterioration warranting further investigation.
Databáze: OpenAIRE
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