The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration - Archive ouverte HAL Access content directly
Journal Articles Nature Medicine Year : 2022

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

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Salam Bashir
  • Function : Author
Cristina Costa
Galli Cesare
Alejandro Ruiz-Majoral
Liana Govani
  • Function : Author
Sharon Yehuda
Ron Amon
  • Function : Author
Hai Yu
Xi Chen
Vered Padler-Karavani
  • Function : Correspondent author
  • 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.
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Dates and versions

inserm-03580771 , version 1 (18-02-2022)

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Thomas Senage, Anu Paul, Thierry Le Tourneau, Imen Fellah-Hebia, Marta Vadori, et al.. The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration. Nature Medicine, 2022, Online ahead of print. ⟨10.1038/s41591-022-01682-w⟩. ⟨inserm-03580771⟩
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