Alpha-Gal Specific IgG Immune Response after Implantation of Bioprostheses

Mangold, Andreas; Szerafin, Tamás; Höetzenecker, Konrad; Hacker, Stefan; Lichtenauer, Michael; Niederpold, Tina; Nickl, Stefanie; Dworschak, Martin; Blumer, Roland; Auer, J.; Ankersmit, Hendrik Jan

doi:10.1055/s-0029-1185395

Cited by 54 publications

(49 citation statements)

References 25 publications

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“…There is experimental evidence that remaining carbohydrate in the tissues is a target for the immune destruction process, which employs anticarbohydrate antibodies. The presence of remaining Galα3 and NeuGc xenoantigens has been described in commercially available BHV, and anti‐αGal antibodies have been shown to be produced in patients grafted with BHVs …”

Section: Introductionmentioning

confidence: 99%

“…The presence of remaining Galα3 3-6 and NeuGc 7 xenoantigens has been described in commercially available BHV, and anti-αGal antibodies have been shown to be produced in patients grafted with BHVs. 3,6,[8][9][10] The amount of animal tissue present in commercial BHVs is extremely small, and this-in combination with the very high costs of these products-has limited studies to primarily immunohistochemistry [3][4][5] or monosaccharide determination. 7 It is therefore not practically possible to obtain sufficient biological material for isolation and detailed structural characterization of potential remaining carbohydrate antigen structures in BHV grafts used clinically.…”

Section: Introductionmentioning

confidence: 99%

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

Barone

Benktander

Whiddon

et al. 2018

Xenotransplantation

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Barone

Benktander

Whiddon

et al. 2018

Xenotransplantation

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“…23, 24 A number of attempts have been made to reduce or inactivate the antigen from tissues to ensure the safety of animal-derived medical products, but only a few have resulted in a practical clinical use. For example, glutaraldehyde-fixed porcine skin or acellular dermal matrix (ADM) has been utilized as a temporary cover for third degree burns.…”

Section: Discussionmentioning

confidence: 99%

Quantification of α-Gal Antigen Removal in the Porcine Dermal Tissue by α-Galactosidase

Gao

Sun

et al. 2015

Tissue Engineering Part C: Methods

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The α-Gal (Galα1,3-Galβ1-4GlcNAc-R) epitope, the major xenoantigen, is the first barrier in a porcine-to-man tissue and organ xenotransplantation. The elimination or reduction of the α-Gal epitopes is therefore an important step for a successful xenotransplantation. The present study is to evaluate the α-Gal elimination in the porcine skin with α-galactosidase treatment, and to assess two methods (immunohistochemistry and inhibition ELISA) that may be used in quality control for quantifying the extent of the α-Gal elimination. Enzymatic cleavage in a single-step process is extremely efficient and affordable at eliminating the α-Gal epitope even in a tissue as dense as the porcine dermis. The cost of enzymatic cleavage is found to be less than US$7 for a 10 × 10 cm piece of porcine skin (0.5 mm thick) or about US$140 for 100 g of 3-dimensional soft tissues. After enzymatic cleavage, the α-Gal-positive immunostaining was essentially undetectable in enzyme-treated porcine skin. The inhibition rate constant of the monoclonal anti-Gal antibody M86 binding to α-Gal-bovine serum albumin in ELISA was reduced from 15.0 ± 4.3 (n = 10) to 6.1 ± 2.6 (n = 7) after enzyme treatment, in comparison to 4.4 ± 1.8 (n = 9) background inhibition of decellularized human skin (the ultimate negative control), which demonstrates ∼ 84% elimination of α-Gal epitopes in treated porcine skin. To examine the suitability of two detection methods for the routine quality control application, comparative studies were made with control and enzyme-treated porcine skin, porcine skin from the α-Gal knockout animal, as well as decellularized human skin. The data show that the traditional immunohistochemistry and, to a less extent, the inhibition ELISA with further modifications can be used as quality control tools in the production and selection of biocompatible bioprosthetic devices. The biological evaluation of enzyme-treated porcine skin is ongoing with a small animal model and a nonhuman primate model.

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“…A further report by Mangold et al [9] highlighted the relevance for Gal-specific immune responses in valve recipients.…”

mentioning

confidence: 94%

From xenograft experiments to xenograft immune responses in cardiac surgery*

Ankersmit¹

2012

Xenotransplantation

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Alpha-Gal Specific IgG Immune Response after Implantation of Bioprostheses

Cited by 54 publications

References 25 publications

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

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

Quantification of α-Gal Antigen Removal in the Porcine Dermal Tissue by α-Galactosidase

From xenograft experiments to xenograft immune responses in cardiac surgery*

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