Evidence map›Paper›PMID 27610947›Full record

ArticleXenotransplantation2016

Characterization of immunogenic Neu5Gc in bioprosthetic heart valves.

Eliran Moshe Reuven, Shani Leviatan Ben-Arye, Tal Marshanski, Michael E Breimer, Hai Yu, Imen Fellah-Hebia, Jean-Christian Roussel, Cristina Costa, Manuel Galiñanes, Rafael Mañez and 5 more

Open access · greenAbstract read
In one paragraph

Article in Xenotransplantation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
9.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 76 citations in OpenAlex.

  1. Review
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  6. Macrophages as key modulators of calcific aortic valve disease.Frontiers in cardiovascular medicine · 2025
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  7. Serum antibody screening using glycan arrays.Chemical Society reviews · 2024
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  10. Oxidative Release ofAnalytical chemistry · 2023
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  16. Review
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  18. Review
  19. Article
  20. Yak Pericardium as an Alternative Biomaterial for Transcatheter Heart Valves.Frontiers in bioengineering and biotechnology · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 9 institutions in 6 countries.

Eliran Moshe ReuvenDepartment of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel.
Shani Leviatan Ben-AryeDepartment of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel.
Tal MarshanskiDepartment of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel.
Michael E BreimerDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Hai YuDepartment of Chemistry, University of California-Davis, Davis, CA, USA.
Imen Fellah-HebiaDepartment of Thoracic and Cardiovascular Surgery, Institut du Thorax, University Hospital, Nantes, France.
Jean-Christian RousselDepartment of Thoracic and Cardiovascular Surgery, Institut du Thorax, University Hospital, Nantes, France.
Cristina CostaInfectious Diseases and Transplantation Division, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
Manuel GaliñanesDepartment of Cardiac Surgery, Reparative Therapy of the Heart, Hospital Universitari Vall d'Hebron and Vall d'Hebron Research Institute, Barcelona, Spain.
Rafael MañezInfectious Diseases and Transplantation Division, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
Thierry Le TourneauDepartment of Cardiology, Institut du Thorax, University Hospital, Nantes, France.
Jean-Paul SoulillouInstitut de Transplantation-Urologie-Néphrologie, INSERM Unité Mixte de Recherche 1064, Centre Hospitalo Universitaire de Nantes, Nantes, France.
Emanuele CozziTransplant Immunology Unit, Department of Transfusion Medicine, Padua University Hospital, Padua, Italy.
Xi ChenDepartment of Chemistry, University of California-Davis, Davis, CA, USA.
Vered Padler-KaravaniDepartment of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel. vkaravani@post.tau.ac.il.
Tel Aviv University · ILInstitut du Thorax · FRUniversity of California, Davis · USBellvitge University Hospital · ESInserm · FRInstitut d'Investigació Biomédica de Bellvitge · ESUniversity of Gothenburg · SEUniversity of Padua · ITVall d'Hebron Institut de Recerca · ES

Funding

Studies of Naturally Occurring Structurally Modified CarbohydratesR01GM076360 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CHEN, XI · 2006 to 2010
$1.9M
NIGMS NIH HHS R01 GM076360
6 · The paper itself

Abstract

backgroundThe 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.

methodsWe 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.

resultsNeu5Gc 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.

conclusionsWe 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.

Indexed as

Transplantation, HeterologousAnimalsAntibodiesBioprosthesisCattleHeart ValvesNeuraminic AcidsPericardiumSwineAntibodiesNeuraminic AcidsN-glycolylneuraminic acidimmunologyNeu5Gctransplantationvalvular heart diseasexeno-antigens

Identifiers

PMID27610947
PMCPMC5036590
OpenAlexW2507761367

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.