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Xenotransplantation2018; 25(5); e12406; doi: 10.1111/xen.12406

Glycosphingolipids of porcine, bovine, and equine pericardia as potential immune targets in bioprosthetic heart valve grafts.

Abstract: Pericardial tissue from various animal species is utilized for the production of the bioprosthetic heart valves (BHV) used clinically. Experimental data show that the eventual breakdown of BHV is partly due to immunological interactions with carbohydrate tissue antigens. To understand these processes, we have examined the glycolipid-based carbohydrate antigens in naïve porcine, bovine, and equine pericardia. Total non-acid and acid glycosphingolipid fractions were isolated from porcine, bovine, and equine pericardia, and individual glycolipid compounds were characterized by thin-layer chromatography, mass spectrometry, and binding of monoclonal antibodies, lectins and bacteria in chromatogram binding assays. The non-acid glycolipid fractions from all species contained glycosphingolipids based on the globo- and neolacto-series, including pentaglycosylceramides with terminal Galα3 determinants. Terminal blood group A and H (O) structures based on type 2 core chains were present in porcine pericardium, while the Forssman pentaosylceramide was found in equine pericardium. All acid glycolipid fractions contained sulfatide and several gangliosides with both N-acetyl- and N-glycolyl-neuraminic acid as terminal saccharide chain determinants. Several carbohydrate antigens which are potential targets for the human immune system have been identified in the animal pericardial tissues used for the production of BHV. Which of these antigens are left in the tissues after industrial BHV production processes, as well as their potential role in eventual BHV degradation, remains to be elucidated.
Publication Date: 2018-06-22 PubMed ID: 29932253DOI: 10.1111/xen.12406Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research investigates the carbohydrate tissue antigens that may cause the eventual breakdown of bioprosthetic heart valves (BHV). The team studied glycolipid-based carbohydrate antigens found within the pericardial tissue from pigs, cows, and horses, with glycolipid compounds being isolated and characterized. The results identified several carbohydrate antigens that could potentially trigger a human immune response.

Research Overview

  • This study focused on bioprosthetic heart valves (BHV) made from pericardial tissue, which is typically sourced from pigs, cows, and horses.
  • The researchers aimed to understand the eventual failure of these BHV, which they believe could be caused, to some extent, by immune responses to the carbohydrate tissue antigens in these animal tissues.

Glycolipid-Based Carbohydrate Antigens

  • In their investigation, they examined the glycolipid-based carbohydrate antigens present within the pericardial tissue of porcine, bovine and equine origins.
  • These glycolipid compounds were isolated and characterized using methods such as thin-layer chromatography, mass spectrometry, and binding of monoclonal antibodies.

Findings and Identification of Carbohydrate Antigens

  • Results showed that the non-acid glycolipid fractions from all species contained glycosphingolipids from the globo- and neolacto-series, including pentaglycosylceramides with terminal Galα3 determinants.
  • Certain specific structures, such as blood group A and H (O) structures based on type 2 core chains, were also found in porcine pericardium, while the Forssman pentaosylceramide was detected in equine pericardium.
  • All acid glycolipid fractions contained sulfatide and several gangliosides with both N-acetyl- and N-glycolyl-neuraminic acid as terminal saccharide chain determinants.

Implication and Further Research

  • The study identified several carbohydrate antigens, present in animal pericardial tissues used for BHV production, that may be targeted by the human immune system.
  • This research sets the groundwork for further investigation into which of these antigens remain in the tissues after the BHV production process, and how they might contribute to the eventual degradation of these valves.

Cite This Article

APA
Barone A, Benktander J, Whiddon C, Jin C, Galli C, Teneberg S, Breimer ME. (2018). Glycosphingolipids of porcine, bovine, and equine pericardia as potential immune targets in bioprosthetic heart valve grafts. Xenotransplantation, 25(5), e12406. https://doi.org/10.1111/xen.12406

Publication

ISSN: 1399-3089
NlmUniqueID: 9438793
Country: Denmark
Language: English
Volume: 25
Issue: 5
Pages: e12406

Researcher Affiliations

Barone, Angela
  • Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Benktander, John
  • Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Whiddon, Christy
  • Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Jin, Chunsheng
  • Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Galli, Cesare
  • Avantea Laboratory of Reproductive Technologies, Cremona, Italy.
Teneberg, Susann
  • Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Breimer, Michael E
  • Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

MeSH Terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Bioprosthesis / parasitology
  • Cattle
  • Glycosphingolipids / metabolism
  • Heart Valve Prosthesis
  • Heart Valves / immunology
  • Heart Valves / pathology
  • Horses
  • Humans
  • Neuraminic Acids / pharmacology
  • Pericardium / immunology
  • Swine
  • Transplantation, Heterologous / methods

Grant Funding

  • Swedish Cancer Foundation
  • Sahlgrenska University Hospital
  • HEALTH-F4-2013-603049 / EU FP7 TransLink Collaborative Project

Citations

This article has been cited 6 times.
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    doi: 10.1007/s10719-020-09931-1pubmed: 32542517google scholar: lookup
  4. Breimer ME, Holgersson J. The Structural Complexity and Animal Tissue Distribution of N-Glycolylneuraminic Acid (Neu5Gc)-Terminated Glycans. Implications for Their Immunogenicity in Clinical Xenografting.. Front Mol Biosci 2019;6:57.
    doi: 10.3389/fmolb.2019.00057pubmed: 31428616google scholar: lookup
  5. Perota A, Lagutina I, Duchi R, Zanfrini E, Lazzari G, Judor JP, Conchon S, Bach JM, Bottio T, Gerosa G, Costa C, Galiñanes M, Roussel JC, Padler-Karavani V, Cozzi E, Soulillou JP, Galli C. Generation of cattle knockout for galactose-α1,3-galactose and N-glycolylneuraminic acid antigens.. Xenotransplantation 2019 Sep;26(5):e12524.
    doi: 10.1111/xen.12524pubmed: 31115108google scholar: lookup
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    doi: 10.1136/bmjopen-2019-029109pubmed: 31061061google scholar: lookup