Xenoimmune Response Can Elicit Postoperative Bioprosthetic Valve Degeneration

Abstract

<h3>Purpose</h3> Bioprosthetic heart valves (BHVs) are widely used for the surgical or interventional treatment of heart valve disease. However, BHVs are prone to structural valve degeneration (SVD), and a certain amount of cases develop SVD during the early postoperative period. Recent studies implicate that the immunogenicity of the BHVs can be an underlying cause of SVD development.In the present study, we investigated whether a xenoimmune response against α-Gal (galactose-alpha-1,3-galactase) is associated with the early deterioration of BHVs or not. <h3>Methods</h3> A total of 392 porcine and bovine BHV explanted at the time of reoperation due to clinically severe SVD between 2015 and 2019 were investigated. Among those, SVD occurred within 2 years from the surgery was defined as early SVD, and that occurred later than 10 yeas was defined as late SVD. The results of immunohistoligical analysis of BHD with early SVD (n=42) were compared with those of late SVD (n=293), the unused BHVs (glutaraldehyde-fixed) provided from the manufacturer, and the degenerated homografts (n=9) also retrieved during reoperation. <h3>Results</h3> Unused BHVs were positive for a-Gal irrespective of glutaraldehyde-fixation. In BHV with early SVD, α-Gal was positive in 72% of the specimen, and T lymphocyte dominant inflammatory cell infiltration was observed. In contrast, in BHV with late SVD, α-Gal was positive in 13% (p<0.01) and the inflammatory cells were mainly macrophages around calcification. The degenerated homografts showed a presence of small number of macrophages and B cells around the calcification but T cells were poorly detected (Figure). <h3>Conclusion</h3> BHV have been considered to be free from xeno-immunogeneity. However, a residual immunogeneity, revealed by a-Gal positivity found in the unused valves, might provoke xenoimmune response of the human immunity against the valve. Our findings suggest the bioprosthetic valve degeneration may be the result of xenograft rejection. Further study is warranted to reveal the exact mechanism of the failure.