title: The immune response to crosslinked tissue is reduced in decellularized xenogeneic and absent in decellularized allogeneic heart valves.
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.
  
  
  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.
authors.affiliation: 2 Division for Cardiothoracic, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover - Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Böer
authors.forename: Ariane
authors.initials: A
authors.lastname: Schridde
authors.forename: Marcel
authors.initials: M
authors.lastname: Anssar
authors.forename: Melanie
authors.initials: M
authors.lastname: Klingenberg
authors.forename: Samir
authors.initials: S
authors.lastname: Sarikouch
authors.forename: Ansgar
authors.initials: A
authors.lastname: Dellmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Harringer
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Mathias
authors.initials: M
authors.lastname: Wilhelmi
mesh_terms: D000917:Antibody Formation / Q000276:immunology; D001672:Biocompatible Materials / Q000494:pharmacology; D001705:Bioprosthesis / Q000009:adverse effects*; D019544:Equipment Failure Analysis; D005500:Follow-Up Studies; D005858:Germany; D006350:Heart Valve Prosthesis / Q000009:adverse effects*; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods; D011183:Postoperative Complications / Q000276:immunology*; D023822:Tissue Engineering / Q000379:methods; D016896:Treatment Outcome; D014694:Ventricular Outflow Obstruction / Q000601:surgery*
chemical_list: D001672:Biocompatible Materials