First quantification of alpha-Gal epitope in current glutaraldehyde-fixed heart valve bioprostheses

Xenotransplantation. 2013 Jul-Aug;20(4):252-61. doi: 10.1111/xen.12044. Epub 2013 Jul 19.

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.

Keywords: antibody/antigen; biomaterials; heart valve bioprosthesis; immunology; xenograft.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology
  • Antigens / immunology
  • Cattle
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epitopes / genetics
  • Epitopes / immunology*
  • Galactosyltransferases / genetics
  • Galactosyltransferases / immunology*
  • Gene Knockout Techniques
  • Glutaral / pharmacology*
  • Graft Rejection / immunology
  • Heart Valve Prosthesis*
  • Heart Valves / drug effects*
  • Heart Valves / immunology*
  • Humans
  • Male
  • Materials Testing
  • Models, Animal
  • Swine
  • Transplantation, Heterologous / methods*

Substances

  • Antibodies, Anti-Idiotypic
  • Antigens
  • Epitopes
  • Galactosyltransferases
  • alpha-1,3-galactosyltransferase 1, porcine
  • Glutaral