The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration.

Animals Antibody Formation Aortic Valve / pathology Aortic Valve Stenosis Bioprosthesis Calcinosis Galactose Humans Immunoglobulin G Mice Polysaccharides Prospective Studies

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
02 2022
Historique:
received: 30 03 2021
accepted: 06 01 2022
pubmed: 19 2 2022
medline: 20 4 2022
entrez: 18 2 2022
Statut: ppublish

Résumé

Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-αGal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-αGal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack αGal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in αGal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability.

Identifiants

DOI: 10.1038/s41591-022-01682-w PMID: 35177855 PMC: PMC8863575
pubmed: 35177855
doi: 10.1038/s41591-022-01682-w
pii: 10.1038/s41591-022-01682-w
pmc: PMC8863575
doi:

Substances chimiques

Immunoglobulin G 0
Polysaccharides 0
Galactose X2RN3Q8DNE

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

283-294

Informations de copyright

© 2022. The Author(s).

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Auteurs

Thomas Senage (T)

Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.
Institut National de la Santé et de la Recherche Médicale UMR 1246-SPHERE, Nantes University, Tours University, Nantes, France.

Anu Paul (A)

Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-2479-8398

Thierry Le Tourneau (T)

Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.

Imen Fellah-Hebia (I)

Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.

Marta Vadori (M)

Consortium for Research in Organ Transplantation, Ospedale Giustinianeo, Padova, Italy.

Salam Bashir (S)

Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Manuel Galiñanes (M)

Department of Cardiac Surgery and Reparative Therapy of the Heart, Vall d'Hebron Research Institute, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Tomaso Bottio (T)

Cardiovascular Regenerative Medicine Group, Department of Cardiac, Thoracic and Vascular Surgery, University of Padova, Padova, Italy.
ORCID: 0000-0001-7299-2983

Gino Gerosa (G)

Department of Cardiac, Vascular and Thoracic Sciences and Public Health University of Padova, L.I.F.E.L.A.B. Program Veneto Region, Padova, Italy.

Arturo Evangelista (A)

Department of Cardiology, Vall d'Hebron Research Institut, Hospital Vall d'Hebron, Barcelona, Spain.

Luigi P Badano (LP)

Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
Department of Cardiology, Neural and Metabolic Sciences, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico, San Luca Hospital, Milan, Italy.

Alberto Nassi (A)

Transplantation Immunology Unit, Padova University Hospital, Padova, Italy.

Cristina Costa (C)

Infectious Diseases and Transplantation Division, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
ORCID: 0000-0002-1837-4268

Galli Cesare (G)

Avantea, Cremona, Italy.
ORCID: 0000-0002-9529-6136

Rizwan A Manji (RA)

Department of Surgery, Max Rady College of Medicine, University of Manitoba Cardiac Sciences Program, St Boniface Hospital, Winnipeg, Manitoba, Canada.
ORCID: 0000-0002-5359-7889

Caroline Cueff de Monchy (C)

Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.

Nicolas Piriou (N)

Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.

Romain Capoulade (R)

Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.

Jean-Michel Serfaty (JM)

Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.

Guillaume Guimbretière (G)

Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.

Etienne Dantan (E)

Institut National de la Santé et de la Recherche Médicale UMR 1246-SPHERE, Nantes University, Tours University, Nantes, France.
ORCID: 0000-0001-7137-5051

Alejandro Ruiz-Majoral (A)

Department of Cardiology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.
ORCID: 0000-0003-1836-5078

Guénola Coste du Fou (G)

Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.

Shani Leviatan Ben-Arye (S)

Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Liana Govani (L)

Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Sharon Yehuda (S)

Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
ORCID: 0000-0003-2826-1061

Shirley Bachar Abramovitch (S)

Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Ron Amon (R)

Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Eliran Moshe Reuven (EM)

Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Yafit Atiya-Nasagi (Y)

Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Israel Institute for Biological Research, Ness Ziona, Israel.

Hai Yu (H)

Department of Chemistry, University of California, Davis, Davis, CA, USA.
ORCID: 0000-0002-4378-0532

Laura Iop (L)

Cardiovascular Regenerative Medicine Group, Department of Cardiac, Thoracic and Vascular Surgery, University of Padova, Padova, Italy.
Department of Cardiac, Vascular and Thoracic Sciences and Public Health University of Padova, L.I.F.E.L.A.B. Program Veneto Region, Padova, Italy.
Department of Cardiac Thoracic and Vascular Sciences and Public Health, University of Padova, Padova, Italy.

Kelly Casós (K)

Department of Cardiac Surgery and Reparative Therapy of the Heart, Vall d'Hebron Research Institute, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Infectious Diseases and Transplantation Division, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Department of Cardiovascular Disease at the Vall d'Hebron Institut Research, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Sebastián G Kuguel (SG)

Infectious Diseases and Transplantation Division, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
ORCID: 0000-0001-7213-6503

Arnau Blasco-Lucas (A)

Department of Cardiac Surgery and Reparative Therapy of the Heart, Vall d'Hebron Research Institute, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Cardiac Surgery Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.
ORCID: 0000-0002-2796-7428

Eduard Permanyer (E)

Department of Cardiac Surgery and Reparative Therapy of the Heart, Vall d'Hebron Research Institute, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Department of Cardiac Surgery, Quironsalud Teknon Heart Institute, Barcelona, Spain.

Fabrizio Sbraga (F)

Cardiac Surgery Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.

Roger Llatjós (R)

Pathology Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.

Gabriel Moreno-Gonzalez (G)

Infectious Diseases and Transplantation Division, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Intensive Care Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.

Melchor Sánchez-Martínez (M)

Mind the Byte, Barcelona, Spain.
Molomics, Barcelona, Spain.
ORCID: 0000-0002-3674-8577

Michael E Breimer (ME)

Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

Jan Holgersson (J)

Institute of Biomedicine, Department of Laboratory Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

Susann Teneberg (S)

Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

Marta Pascual-Gilabert (M)

Institut Universitari de Ciència i Tecnologia (Inkemia Group), Barcelona, Spain.

Alfons Nonell-Canals (A)

Mind the Byte, Barcelona, Spain.
DevsHealth, Barcelona, Spain.

Yasuhiro Takeuchi (Y)

Division of Infection and Immunity, University College London, London, UK.

Xi Chen (X)

Department of Chemistry, University of California, Davis, Davis, CA, USA.
ORCID: 0000-0002-3160-614X

Rafael Mañez (R)

Infectious Diseases and Transplantation Division, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. rmanez@bellvitgehospital.cat.
Intensive Care Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain. rmanez@bellvitgehospital.cat.
ORCID: 0000-0002-0884-5564

Jean-Christian Roussel (JC)

Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France. jeanchristian.roussel@chu-nantes.fr.
ORCID: 0000-0003-3928-6977

Jean-Paul Soulillou (JP)

Institut de Transplantation-Urologie-Néphrologie, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1064, Centre Hospitalier Universitaire de Nantes, Nantes, France. jean-paul.soulillou@univ-nantes.fr.
ORCID: 0000-0001-7468-5135

Emanuele Cozzi (E)

Transplantation Immunology Unit, Padova University Hospital, Padova, Italy. emanuele.cozzi@unipd.it.
ORCID: 0000-0001-7855-5055

Vered Padler-Karavani (V)

Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. vkaravani@tauex.tau.ac.il.
ORCID: 0000-0002-4761-3571

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › The role of antibody responses against glycans...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité acquise › Immunité active › Production d'anticorps › The role of antibody responses against glycans...
questionsmedicales.fr › Système cardiovasculaire › Coeur › Valves cardiaques › Valve aortique › The role of antibody responses against glycans...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Obstacle à l'éjection ventriculaire › Sténose aortique › The role of antibody responses against glycans...
questionsmedicales.fr › Équipement et fournitures › Prothèses et implants › Bioprothèse › The role of antibody responses against glycans...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles du métabolisme du calcium › Calcinose › The role of antibody responses against glycans...
questionsmedicales.fr › Glucides › Sucres › Oses › Hexose › Galactose › The role of antibody responses against glycans...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The role of antibody responses against glycans...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline G › The role of antibody responses against glycans...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › The role of antibody responses against glycans...
questionsmedicales.fr › Glucides › Polyosides › The role of antibody responses against glycans...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › The role of antibody responses against glycans...