Differential Immune Response to Bioprosthetic Heart Valve Tissues in the α1,3Galactosyltransferase-Knockout Mouse Model

Kelly Casós, Roger Llatjós, Arnau Blasco-Lucas, Sebastián G. Kuguel, Fabrizio Sbraga, Cesare Galli, Vered Padler-Karavani, Thierry Le Tourneau, Marta Vadori, Andrea Perota, Jean Christian Roussel, Tomaso Bottio, Emanuele Cozzi, Jean Paul Soulillou, Manuel Galiñanes, Rafael Máñez, Cristina Costa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Structural valve deterioration (SVD) of bioprosthetic heart valves (BHVs) has great clinical and economic consequences. Notably, immunity against BHVs plays a major role in SVD, especially when implanted in young and middle-aged patients. However, the complex pathogenesis of SVD remains to be fully characterized, and analyses of commercial BHVs in standardized-preclinical settings are needed for further advancement. Here, we studied the immune response to commercial BHV tissue of bovine, porcine, and equine origin after subcutaneous implantation into adult α1,3-galactosyltransferase-knockout (Gal KO) mice. The levels of serum anti-galactose α1,3-galactose (Gal) and -non-Gal IgM and IgG antibodies were determined up to 2 months post-implantation. Based on histological analyses, all BHV tissues studied triggered distinct infiltrating cellular immune responses that related to tissue degeneration. Increased anti-Gal antibody levels were found in serum after ATS 3f and Freedom/Solo implantation but not for Crown or Hancock II grafts. Overall, there were no correlations between cellular-immunity scores and post-implantation antibodies, suggesting these are independent factors differentially affecting the outcome of distinct commercial BHVs. These findings provide further insights into the understanding of SVD immunopathogenesis and highlight the need to evaluate immune responses as a confounding factor.

Original languageEnglish
Article number833
JournalBioengineering
Volume10
Issue number7
DOIs
StatePublished - Jul 2023

Funding

FundersFunder number
Seventh Framework Programme603049
Federación Española de Enfermedades Raras
Ministerio de Economía y CompetitividadPI15/00181, SLT002/16/00445
Seventh Framework Programme
Departament de Salut, Generalitat de Catalunya

    Keywords

    • anti-Gal antibodies
    • bioprosthetic heart valves
    • cellular immune infiltrate
    • structural valve deterioration
    • α1,3-galactosyltransferase-knockout mice

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