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Cited by 82Xenotransplantation and immune responseGlycosylation and Glycoproteins ResearchBlood groups and transfusion

Characteristics of α-Gal epitope, anti-Gal antibody, α1,3 galactosyltransferase and its clinical exploitation (Review)

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HUAI, GUOLI, QI, PING, YANG, HONGJI, WANG, YI·2016·International Journal of Molecular Medicine
DOI 10.3892/ijmm.2015.2397PMC PMC4687435
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Abstract

The α-Gal epitope (Galα1,3Galα1,4GlcNAc‑R) is ubiquitously presented in non-primate mammals, marsupials and New World Monkeys, but it is absent in humans, apes and Old World monkeys. However, the anti-Gal antibody (~1% of immunoglobulins) is naturally generated in human, and is found as the immunoglobulin G (IgG), IgM and IgA isotypes. Owing to the specific binding of the anti‑Gal antibody with the α‑Gal epitope, humans have a distinct anti‑α‑gal reactivity, which is responsible for hyperacute rejection of organs transplanted from α‑gal donors. In addition, the α1,3 galactosyltransferases (α1,3GT) can catalyze the synthesis of the α‑Gal epitope. Therefore, the α1,3GT gene, which encodes the α1,3GT, is developed profoundly. The distributions of the α‑Gal epitope and anti‑Gal antibody, and the activation of α1,3GT, reveal that the enzyme of α1,3GT in ancestral primates is ineffective. Comparison of the nucleotide sequence of the human α1,3‑GT pseudogene to the corresponding different species sequence, and according to the evolutionary tree of different species, the results of evolutionary inactivation of the α1,3GT gene in ancestral primates attribute to the mutations under a stronger selective pressure. However, on the basis of the structure, the mechanism and the specificity of the α‑Gal epitope and anti‑Gal antibody, they can be applied to clinical exploitation. Knocking out the α1,3GT gene will eliminate the xenoantigen, Gal(α1,3)Gal, so that the transplantation of α1,3GT gene knockout pig organ into human becomes a potential clinically acceptable treatment for solving the problem of organ shortage. By contrast, the α‑Gal epitope expressed through the application of chemical, biochemical and genetic engineering can be exploited for the clinical use. Targeting anti‑Gal‑mediated autologous tumor vaccines, which express α‑Gal epitope to antigen‑presenting cells, would increase their immunogenicity and elicit an immune response, which will be potent enough to eradicate the residual tumor cells. For tumor vaccines, the way of increasing immunogenicity of certain viral vaccines, including flu vaccines and human immunodeficiency virus vaccines, can also be used in the elderly. Recently, α‑Gal epitope nanoparticles have been applied to accelerate wound healing and further directions on regeneration of internally injured tissues.

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  • Immunogenic carbohydrates are mainly found in cell membranes, although some presence can be observed in ECM proteins depending on the tissue.

    “these immunogenic carbohydrates are mainly found in cell membranes [162], although some presence can be observed in ECM proteins in function of the tissue.”

    From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [162]

    The Introduction and §2 (α-Gal epitope; page unavailable) describe α-Gal on red-cell membrane glycolipids and cell-surface glycoproteins. The source does not establish that these carbohydrates are mainly found in cell membranes. It also mentions α-Gal on laminin, but does not compare its presence in ECM proteins across tissues. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Some carbohydrates such as the α-gal epitope are well-known to activate pro-inflammatory responses.

    “While some carbohydrates such as the α-gal epitope are well-known to activate pro-inflammatory responses, these immunogenic carbohydrates are mainly found in cell membranes [162]”

    From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [162]

    The Clinical exploitation section (page unavailable) says that anti-Gal binding to the α-Gal epitope activates complement and recruits macrophages, supporting the claim about an inflammatory response. The Introduction and α-Gal epitope section describe membrane-associated examples, but also identify the epitope on other molecules; they do not establish that these carbohydrates are mainly found in cell membranes. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Contradictory results about α-gal may be explained by variance of α-gal expression in different tissues and organs.

    “These contradictory results may be explained by the variance of α-gal expression in different tissues and organs [125].”

    From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [125]

    Section 2 (‘α-Gal epitope’; page not available) reports substantial differences in α-Gal abundance between organs and among kidney structures. The review does not say that this variation explains the contradictory results mentioned by the citing authors. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Several studies have suggested α-gal epitopes as the source of chronic rejection and calcification in bioprosthetic heart valves.

    “Likewise, several studies have suggested α-gal epitopes as the source of chronic rejection and calcification in bioprosthetic heart valves [125–127].”

    From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [125]

    The Xenotransplantation section (page unavailable) says that α-Gal on bioprosthetic heart valves contributes to an immune response and discusses a possible immune role in their calcification. It does not identify α-Gal as a source of chronic rejection of those valves; its discussion of rejection concerns hyperacute or delayed xenograft rejection. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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References 90 · Cited by 82

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Authors
HUAI, G., QI, P., YANG, H., & WANG, Y.
Affiliations
  • University of Electronic Science and Technology of China (CN)
  • Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (CN)
Corresponding author
  • YANG, HONGJI
  • WANG, YI
ORCID
Venue
International Journal of Molecular Medicine
Publisher
Spandidos Publications
Published
2015-10-30
Volume
37
Issue
1
Pages
11-20
ISSN
  • 1107-3756 (ISSN-L)
  • 1791-244X
DOI
10.3892/ijmm.2015.2397
PMC
PMC4687435
OpenAlex
W1830480933
Cited by
82
References
90
Citations by year
2026: 2 · 2025: 8 · 2024: 13 · 2023: 10 · 2022: 12 · 2021: 6 · 2020: 16 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 2
FWCI
0.57
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • International Journal of Molecular Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Natural Science Foundation of Sichuan Province
Topics
  • Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Health Sciences › Medicine › Hematology › Blood groups and transfusion
Keywords
anti-Gal antibodies, alpha-1,3-galactosyltransferase, hyperacute rejection, xenotransplantation, xenoantigens, gene knockout, vaccine immunogenicity, influenza vaccination, HIV vaccine, immunosenescence
MeSH terms
Animals, Antibodies, Epitopes, Base Sequence, Biological Evolution, Galactosyltransferases, Graft Rejection, Humans, Immunotherapy, Molecular Sequence Data, Neoplasms, Regeneration, Transplantation, Heterologous, Trisaccharides, Wound Healing, Gene Knockout Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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