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

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.

SUBMITTER: Senage T

PROVIDER: S-EPMC8863575 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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

Senage Thomas T Paul Anu A Le Tourneau Thierry T Fellah-Hebia Imen I Vadori Marta M Bashir Salam S Galiñanes Manuel M Bottio Tomaso T Gerosa Gino G Evangelista Arturo A Badano Luigi P LP Nassi Alberto A Costa Cristina C Cesare Galli G Manji Rizwan A RA Cueff de Monchy Caroline C Piriou Nicolas N Capoulade Romain R Serfaty Jean-Michel JM Guimbretière Guillaume G Dantan Etienne E Ruiz-Majoral Alejandro A Coste du Fou Guénola G Leviatan Ben-Arye Shani S Govani Liana L Yehuda Sharon S Bachar Abramovitch Shirley S Amon Ron R Reuven Eliran Moshe EM Atiya-Nasagi Yafit Y Yu Hai H Iop Laura L Casós Kelly K Kuguel Sebastián G SG Blasco-Lucas Arnau A Permanyer Eduard E Sbraga Fabrizio F Llatjós Roger R Moreno-Gonzalez Gabriel G Sánchez-Martínez Melchor M Breimer Michael E ME Holgersson Jan J Teneberg Susann S Pascual-Gilabert Marta M Nonell-Canals Alfons A Takeuchi Yasuhiro Y Chen Xi X Mañez Rafael R Roussel Jean-Christian JC Soulillou Jean-Paul JP Cozzi Emanuele E Padler-Karavani Vered V

Nature medicine 20220217 2

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 int ...[more]

PMID: 35177855

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Project description:Background Mechanisms underlying bioprosthetic valve deterioration are multifactorial and incompletely elucidated. Reparative circulating progenitor cells, and conversely calcification-associated osteocalcin expressing circulating progenitor cells, have been linked to native aortic valve deterioration. However, their role in bioprosthetic valve deterioration remains elusive. This study sought to evaluate the contribution of different subpopulations of circulating progenitor cells in bioprosthetic valve deterioration. Methods and Results This single-center prospective study enrolled 121 patients who had peripheral blood mononuclear cells isolated before bioprosthetic aortic valve replacement and had an echocardiographic follow-up ≥2 years after the procedure. Using flow cytometry, fresh peripheral blood mononuclear cells were analyzed for the surface markers CD34, CD133, and osteocalcin. Bioprosthetic valve deterioration was evaluated by hemodynamic valve deterioration (HVD) using echocardiography, which was defined as an elevated mean transprosthetic gradient ≥30 mm Hg or at least moderate intraprosthetic regurgitation. Sixteen patients (13.2%) developed HVD during follow-up for a median of 5.9 years. Patients with HVD showed significantly lower levels of reparative CD34+CD133+ cells and higher levels of osteocalcin-positive cells than those without HVD (CD34+CD133+ cells: 125 [80, 210] versus 270 [130, 420], P=0.002; osteocalcin-positive cells: 3060 [523, 5528] versus 670 [180, 1930], P=0.005 respectively). Decreased level of CD34+CD133+ cells was a significant predictor of HVD (hazard ratio, 0.995 [95% CI, 0.990%-0.999%]). Conclusions Circulating levels of CD34+CD133+ cells and osteocalcin-positive cells were significantly associated with the subsequent occurrence of HVD in patients undergoing bioprosthetic aortic valve replacement. Circulating progenitor cells might play a vital role in the mechanism, risk stratification, and a potential therapeutic target for patients with bioprosthetic valve deterioration.

Dataset Information

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

Publications

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

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