The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration
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Anu Paul
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- PersonId : 822969
- ORCID : 0000-0003-2479-8398
Tomaso Bottio
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- ORCID : 0000-0001-7299-2983
Cristina Costa
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- PersonId : 795356
- ORCID : 0000-0002-1837-4268
Galli Cesare
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- PersonId : 822970
- ORCID : 0000-0002-9529-6136
Rizwan Manji
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- PersonId : 822971
- ORCID : 0000-0002-5359-7889
Etienne Dantan
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- PersonId : 177854
- IdHAL : etienne-dantan
- ORCID : 0000-0001-7137-5051
- IdRef : 139602739
Alejandro Ruiz-Majoral
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- PersonId : 822972
- ORCID : 0000-0003-1836-5078
Hai Yu
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- PersonId : 764743
- ORCID : 0000-0002-4378-0532
Sebastián Kuguel
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- PersonId : 822973
- ORCID : 0000-0001-7213-6503
Arnau Blasco-Lucas
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- ORCID : 0000-0002-2796-7428
Melchor Sánchez-Martínez
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- ORCID : 0000-0002-3674-8577
Xi Chen
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- PersonId : 758843
- ORCID : 0000-0002-3160-614X
Rafael Mañez
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- PersonId : 795357
- ORCID : 0000-0002-0884-5564
- IdRef : 162057172
Jean-Christian Roussel
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Jean-Paul Soulillou
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Emanuele Cozzi
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Vered Padler-Karavani
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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