title: First quantification of alpha-Gal epitope in current glutaraldehyde-fixed heart valve bioprostheses.
abstract: BACKGROUND
  Glutaraldehyde fixation does not guarantee complete tissue biocompatibility in current clinical bioprosthetic heart valves (BHVs). Particularly, circulating anti-αGal human antibodies increase significantly from just 10 days after a BHV implantation. The inactivation of such epitope should be mandatory to meet the requirements for a perspectively safe clinical application; nevertheless, its quantitative assessment in commercially available BHVs has never been carried out.
  
  
  METHODS
  In this investigation, seven different models of BHVs were tested. The number of epitopes was determined with reference to a standard αGal source by an ELISA test. The presence of xenoantigen was subsequently confirmed by immunofluorescence analysis. Porcine tissue, knockout for the αGal epitopes, was used as negative control.
  
  
  RESULTS
  Epic™ valve was the only model among those tested, in which the αGal antigen appeared to be completely shielded. Composite Trifecta™ valve exhibited conflicting results: cusps of bovine pericardial tissue were devoid of reactive αGal epitopes, while the stent cover strip of porcine pericardium still maintained 30% of active antigens originally present in native tissue. All other tested BHVs express an αGal amount not significantly different from that exhibited by porcine Mosaic(®) valve (5.2 ± 0.6 × 10(10) each 10 mg of tissue).
  
  
  CONCLUSIONS
  For the first time, the quantitative evaluation of the αGal epitope in heart valve bioprostheses, already in clinical practice for about 40 yrs, was finally determined. Such quantification might provide indications of biocompatibility relevant for the selection of bioprosthetic devices and an increase in the confidence of the patient. It might become a major quality control tool in the production and redirection of future investigation in the quest for αGal-free long-lasting substitutes.
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy. fnaso@bio.unipd.it
authors.forename: Filippo
authors.initials: F
authors.lastname: Naso
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gandaglia
authors.forename: Tomaso
authors.initials: T
authors.lastname: Bottio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tarzia
authors.forename: Mark B
authors.initials: MB
authors.lastname: Nottle
authors.forename: Anthony J F
authors.initials: AJ
authors.lastname: d'Apice
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cowan
authors.forename: Emmanuele
authors.initials: E
authors.lastname: Cozzi
authors.forename: Cesare
authors.initials: C
authors.lastname: Galli
authors.forename: Irina
authors.initials: I
authors.lastname: Lagutina
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lazzari
authors.forename: Laura
authors.initials: L
authors.lastname: Iop
authors.forename: Michele
authors.initials: M
authors.lastname: Spina
authors.forename: Gino
authors.initials: G
authors.lastname: Gerosa
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005700:Galactosyltransferases / Q000235:genetics / Q000276:immunology*; D055786:Gene Knockout Techniques; D005976:Glutaral / Q000494:pharmacology*; D006084:Graft Rejection / Q000276:immunology; D006350:Heart Valve Prosthesis; D006351:Heart Valves / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D008297:Male; D008422:Materials Testing; D023421:Models, Animal; D013552:Swine; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D000939:Epitopes; D005700:Galactosyltransferases; C530267:alpha-1,3-galactosyltransferase 1, porcine; D005976:Glutaral
keywords: antibody/antigen; biomaterials; heart valve bioprosthesis; immunology; xenograft