The immune response to crosslinked tissue is reduced in decellularized xenogeneic and absent in decellularized allogeneic heart valves

Int J Artif Organs. 2015 Apr;38(4):199-209. doi: 10.5301/ijao.5000395. Epub 2015 Apr 21.

Abstract

Background: The degeneration and failure of xenogeneic heart valves, such as the Matrix P Plus valve (MP-V) consisting of decellularized porcine valves (dec-pV) and equine glutaraldehyde-fixed conduits (ga-eC) have been linked to tissue immunogenicity accompanied by antibody formation. In contrast, decellularized allograft valves (dec-aV) are well-tolerated. Here, we determined tissue-specific antibody levels in patients after implantation of MP-V or dec-aV and related them to valve failure or time period after implantation.

Methods and results: Specific antibodies toward whole tissue-homogenates or alphaGal were determined retrospectively by ELISA analyses from patients who received MP-V with an uneventful course of 56.1 ± 5.1 months (n = 15), or with valve failure after 25.3 ± 14.6 months (n = 3), dec-aV for various times from 4 to 46 months (n = 14, uneventful) and from healthy controls (n = 4). All explanted valves were assessed histopathologically.MP-V induced antibodies toward both tissue components with significantly higher levels toward ga-eC than toward dec-pV (68.7 and 26.65 µg/ml IgG). In patients with valve failure, levels were not significantly higher and were related to inflammatory tissue infiltration. Anti-Gal antibodies in MP-V patients were significantly increased in both, the uneventful and the failure group. In contrast, in dec-aV patients only a slight tissue-specific antibody formation was observed after 4 months (6.24 µg/ml) that normalized to control levels after 1 year.

Conclusions: The strong humoral immune response to glutaraldehyde-fixed tissues is reduced in decellularized xenogeneic valves and almost absent in decellularized allogeneic tissue up to 4.5 years after implantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Formation / immunology
  • Biocompatible Materials / pharmacology
  • Bioprosthesis / adverse effects*
  • Equipment Failure Analysis
  • Follow-Up Studies
  • Germany
  • Heart Valve Prosthesis / adverse effects*
  • Heart Valve Prosthesis Implantation* / adverse effects
  • Heart Valve Prosthesis Implantation* / methods
  • Humans
  • Immunity, Humoral / immunology*
  • Inflammation / immunology
  • Male
  • Middle Aged
  • Monitoring, Immunologic / methods
  • Postoperative Complications / immunology*
  • Tissue Engineering / methods
  • Treatment Outcome
  • Ventricular Outflow Obstruction / surgery*

Substances

  • Biocompatible Materials