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Cited by 58Xenotransplantation and immune responseBlood groups and transfusionGlycosylation and Glycoproteins Research

Anti-Neu5Gc and anti-non-Neu5Gc antibodies in healthy humans

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Gao, Bingsi, Long, Cassandra, Lee, Whayoung, Zhang, Zhongqiang, Gao, Xiaotian, Landsittel, Doug, Ezzelarab, Mohamed, Ayares, David +4 more·2017·PLOS ONE
DOI 10.1371/journal.pone.0180768PMC PMC5513429
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Abstract

Our group previously investigated the levels of anti-Gal and anti-nonGal IgM and IgG in a cohort of 75 healthy humans of various backgrounds, and found some significant differences related to factors such as age, gender, ABO blood group, diet, vaccination history, and geographic location during childhood. We have now expanded our cohort (n = 84) to investigate the levels of anti-Neu5Gc and anti-nonGal/nonNeu5Gc antibodies in healthy humans. Anti-nonGal and anti-nonGal/nonNeu5Gc human IgM and IgG binding to pRBCs and pAECs from GTKO/CD46 and GTKO/CD46/Neu5GcKO pigs were measured by flow cytometry. Anti-Gal and anti-Neu5Gc IgM and IgG levels were measured by ELISA. In summary, (i) the great majority (almost 100%) of humans had anti-Neu5Gc IgM and IgG antibodies that bound to pAECs and approximately 50% had anti-Neu5Gc antibodies that bound to pRBCs, (ii) there was significantly less human antibody binding to pig cells that did not express either Gal or Neu5Gc compared with those that did not express Gal alone, (iii) the levels of both IgM and IgG binding to GTKO/CD46/Neu5GcKO pRBCs and pAECs were low, (iv) the level of anti-Neu5Gc IgG was higher in men than women, (v) the level did not change with age or diet, and there was some variability associated with (vi) previous vaccination history and (vii) the geographic region in which the individual spent his or her childhood. Our study confirms that human antibody binding to RBCs and AECs from GTKO/CD46/Neu5GcKO pigs is greatly reduced compared to binding to GTKO/CD46 cells. However, all humans appear to have a low level of antibody that binds to pAECs that is not directed to either Gal or Neu5Gc. Our findings require consideration in planning clinical trials of xenotransplantation.

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  • Xenogeneic sialic acids are one of the leading non-α-gal antigens, participating in the rejection of xenografts.

    “Xenogeneic sialic acids are one of the leading non-α-gal antigens, participating in the rejection of xenografts [133–135].”

    From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [135]

    The Results report that removing Neu5Gc from pig cells already lacking Gal substantially reduced human antibody binding, supporting Neu5Gc as an important non-Gal antigen. The paper does not establish that Neu5Gc participates in xenograft rejection; its findings concern antibody binding to cells, not graft rejection. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Gao, B., Long, C., Lee, W., Zhang, Z., Gao, X., Landsittel, D., Ezzelarab, M., Ayares, D., Huang, Y., Cooper, D. K. C., Wang, Y., & Hara, H.
Affiliations
  • University of Pittsburgh (US)
  • Central South University (CN)
  • University of South China (CN)
Corresponding author
  • Wang, Yi
  • Hara, Hidetaka
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2017-07-17
Volume
12
Issue
7
Pages
e0180768
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0180768
PMC
PMC5513429
OpenAlex
W2735827335
Cited by
58
References
2
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 8 · 2021: 3 · 2020: 13 · 2019: 15 · 2018: 2 · 2017: 2 · 2013: 1
FWCI
8.97
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
National Institutes of Health (U19 AI090959, U01 AI068642, R21 A1074844)
Topics
  • Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
  • Health Sciences › Medicine › Hematology › Blood groups and transfusion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
Keywords
anti-Neu5Gc antibodies, anti-Gal antibodies, xenotransplantation, xenotransplantation rejection, porcine aortic endothelial cells, history of vaccination
MeSH terms
ABO Blood-Group System, Adult, Aged, Aged, 80 and over, Animals, Antibodies, Cells, Cultured, Diet, Erythrocytes, Female, Galactose, Galactosyltransferases, Humans, Mixed Function Oxygenases, Immunoglobulin G, Immunoglobulin M, Male, Middle Aged, Neuraminic Acids, Swine, Vaccination, Endothelial Cells, Membrane Cofactor Protein, Young Adult

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