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Antibody formation towards porcine tissue in patients implanted with crosslinked heart valves is directed to antigenic tissue proteins and αGal epitopes and is reduced in healthy vegetarian subjects.
- Source :
-
Xenotransplantation [Xenotransplantation] 2017 Mar; Vol. 24 (2). Date of Electronic Publication: 2017 Jan 18. - Publication Year :
- 2017
-
Abstract
- Background: Glutaraldehyde-fixed porcine heart valves (ga-pV) are one of the most frequently used substitutes for insufficient aortic and pulmonary heart valves which, however, degenerate after 10-15 years. Yet, xeno-immunogenicity of ga-pV in humans including identification of immunogens still needs to be investigated. We here determined the immunogenicity of ga-pV in patients with respect to antibody formation, identity of immunogens and potential options to reduce antibody levels.<br />Methods: Levels of tissue-specific and anti-αGal antibodies were determined retrospectively in patients who received ga-pV for 51 months (n=4), 25 months (n=6) or 5 months (n=4) and compared to age-matched untreated subjects (n=10) or younger subjects with or without vegetarian diet (n=12/15). Immunogenic proteins were investigated by Western blot approaches.<br />Results: Tissue-specific antibodies in patients were elevated after 5 (1.73-fold) and 25 (1.46-fold, both P<.0001) months but not after 51 months, whereas anti-Gal antibodies were induced 4.75-fold and 3.66-fold after 5 and 25 months (both P<.0001) and still were significantly elevated after 51 months (2.85-fold, P<.05). Western blots of porcine valve extracts with and without enzymatic deglycosylation revealed strong specific staining at ≈65 and ≈140 kDa by patient sera in either group which were identified by 2D Western blots and mass spectrometry as serum albumin and collagen 6A1. Vegetarian diet reduced significantly (0.63-fold, P<.01) the level of pre-formed αGal but not of tissue-specific antibodies.<br />Conclusion: Immune response in patients towards ga-pV is induced by the porcine proteins albumin and collagen 6A1 as well as αGal epitopes, which seemed to be more sustained. In contrast, in healthy young subjects pre-formed anti-Gal antibodies were reduced by a meat-free nutrition.<br /> (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Adult
Aged
Animals
Female
Heart Valves drug effects
Heart Valves transplantation
Humans
Male
Middle Aged
Retrospective Studies
Swine
Transplantation, Heterologous methods
Vegetarians
Antibodies immunology
Antibody Formation immunology
Epitopes immunology
Glutaral pharmacology
Graft Rejection immunology
Heart Valves immunology
alpha-Galactosidase immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1399-3089
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Xenotransplantation
- Publication Type :
- Academic Journal
- Accession number :
- 28101961
- Full Text :
- https://doi.org/10.1111/xen.12288