The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration
Thomas Senage
(1, 2)
,
Anu Paul
(3, 4)
,
Thierry Le Tourneau
(1)
,
Imen Fellah-Hebia
(1)
,
Marta Vadori
(5)
,
Salam Bashir
(3)
,
Manuel Galiñanes
(6)
,
Tomaso Bottio
(5)
,
Gino Gerosa
(5)
,
Arturo Evangelista
(7)
,
Luigi Badano
(8, 9)
,
Alberto Nassi
(5)
,
Cristina Costa
(10)
,
Galli Cesare
(11)
,
Rizwan Manji
(12)
,
Caroline Cueff de Monchy
(1)
,
Nicolas Piriou
(1)
,
Romain Capoulade
(1)
,
Jean-Michel Serfaty
(1)
,
Guillaume Guimbretière
(1)
,
Etienne Dantan
(2)
,
Alejandro Ruiz-Majoral
(10)
,
Guénola Coste Du Fou
(1)
,
Shani Leviatan Ben-Arye
(3)
,
Liana Govani
(3)
,
Sharon Yehuda
(3)
,
Shirley Bachar Abramovitch
(3)
,
Ron Amon
(3)
,
Eliran Moshe Reuven
(3)
,
Yafit Atiya-Nasagi
(3, 13)
,
Hai Yu
(14)
,
Laura Iop
(5)
,
Kelly Casós
(6, 15)
,
Sebastián Kuguel
(15)
,
Arnau Blasco-Lucas
(6, 10)
,
Eduard Permanyer
(6, 16)
,
Fabrizio Sbraga
(10)
,
Roger Llatjós
(10)
,
Gabriel Moreno-Gonzalez
(10, 15)
,
Melchor Sánchez-Martínez
(17, 18)
,
Michael Breimer
(19)
,
Jan Holgersson
(19)
,
Susann Teneberg
(19)
,
Marta Pascual-Gilabert
(20)
,
Alfons Nonell-Canals
(17, 21)
,
Yasuhiro Takeuchi
(22)
,
Xi Chen
(14)
,
Rafael Mañez
(15, 23)
,
Jean-Christian Roussel
(1)
,
Jean-Paul Soulillou
(24)
,
Emanuele Cozzi
(5)
,
Vered Padler-Karavani
(3)
1
ITX -
unité de recherche de l'institut du thorax UMR1087 UMR6291
2 SPHERE - MethodS in Patients-centered outcomes and HEalth ResEarch
3 TAU - Tel Aviv University
4 BWH - Brigham & Women’s Hospital [Boston]
5 Unipd - Università degli Studi di Padova = University of Padua
6 UAB - Universitat Autònoma de Barcelona
7 Vall d'Hebron University Hospital [Barcelona]
8 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
9 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
10 Llobregat Hospital [Barcelona]
11 Fondazione Avantea [Cremona, Italy]
12 St. Boniface Hospital Albrechtsen Research Centre [Winnipeg]
13 IIBR - Israel Institute for Biological Research
14 UC Davis - University of California [Davis]
15 IDIBELL - Institut d'Investigació Biomèdica de Bellvitge [Barcelone]
16 QTHI - Quironsalud Teknon Heart Institute [Barcelona, Spain]
17 Mind the Byte [Barcelona, Spain]
18 Molomics [Barcelona, Spain]
19 Sahlgrenska Academy at University of Gothenburg [Göteborg]
20 (Inkemia Group) IUCT - Institut Universitari de Ciència i Tecnologia [Barcelona, Spain]
21 DH - DevsHealth [Barcelona, Spain]
22 UCL - University College of London [London]
23 Bellvitge University Hospital [Barcelona, Spain]
24 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
2 SPHERE - MethodS in Patients-centered outcomes and HEalth ResEarch
3 TAU - Tel Aviv University
4 BWH - Brigham & Women’s Hospital [Boston]
5 Unipd - Università degli Studi di Padova = University of Padua
6 UAB - Universitat Autònoma de Barcelona
7 Vall d'Hebron University Hospital [Barcelona]
8 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
9 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
10 Llobregat Hospital [Barcelona]
11 Fondazione Avantea [Cremona, Italy]
12 St. Boniface Hospital Albrechtsen Research Centre [Winnipeg]
13 IIBR - Israel Institute for Biological Research
14 UC Davis - University of California [Davis]
15 IDIBELL - Institut d'Investigació Biomèdica de Bellvitge [Barcelone]
16 QTHI - Quironsalud Teknon Heart Institute [Barcelona, Spain]
17 Mind the Byte [Barcelona, Spain]
18 Molomics [Barcelona, Spain]
19 Sahlgrenska Academy at University of Gothenburg [Göteborg]
20 (Inkemia Group) IUCT - Institut Universitari de Ciència i Tecnologia [Barcelona, Spain]
21 DH - DevsHealth [Barcelona, Spain]
22 UCL - University College of London [London]
23 Bellvitge University Hospital [Barcelona, Spain]
24 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
Anu Paul
- Function : Author
- PersonId : 822969
- ORCID : 0000-0003-2479-8398
Tomaso Bottio
- Function : Author
- PersonId : 795416
- ORCID : 0000-0001-7299-2983
Cristina Costa
- Function : Author
- PersonId : 795356
- ORCID : 0000-0002-1837-4268
Galli Cesare
- Function : Author
- PersonId : 822970
- ORCID : 0000-0002-9529-6136
Rizwan Manji
- Function : Author
- PersonId : 822971
- ORCID : 0000-0002-5359-7889
Etienne Dantan
- Function : Author
- PersonId : 177854
- IdHAL : etienne-dantan
- ORCID : 0000-0001-7137-5051
- IdRef : 139602739
Alejandro Ruiz-Majoral
- Function : Author
- PersonId : 822972
- ORCID : 0000-0003-1836-5078
Hai Yu
- Function : Author
- PersonId : 764743
- ORCID : 0000-0002-4378-0532
Sebastián Kuguel
- Function : Author
- PersonId : 822973
- ORCID : 0000-0001-7213-6503
Arnau Blasco-Lucas
- Function : Author
- PersonId : 822974
- ORCID : 0000-0002-2796-7428
Melchor Sánchez-Martínez
- Function : Author
- PersonId : 822975
- ORCID : 0000-0002-3674-8577
Xi Chen
- Function : Author
- PersonId : 758843
- ORCID : 0000-0002-3160-614X
Rafael Mañez
- Function : Author
- PersonId : 795357
- ORCID : 0000-0002-0884-5564
- IdRef : 162057172
Jean-Christian Roussel
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- Function : Correspondent author
- PersonId : 1141175
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Jean-Paul Soulillou
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- Function : Correspondent author
- PersonId : 1048250
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Emanuele Cozzi
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- Function : Correspondent author
- PersonId : 1141176
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Vered Padler-Karavani
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- PersonId : 1107085
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Abstract
Abstract 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.
Domains
Life Sciences [q-bio]
Origin : Publication funded by an institution