Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid
Open accessAbstract
Humans are genetically unable to produce the sialic acid N-glycolylneuraminic acid (Neu5Gc), because of a mutation that occurred after our last common ancestor with great apes. Although Neu5Gc is presumed absent from normal humans, small amounts have been claimed to exist in human tumors and fetal meconium. We have generated an antibody with high specificity and avidity for Neu5Gc. Fetal tissues, normal adult tissues, and breast carcinomas from humans showed reactivity to this antibody, primarily within secretory epithelia and blood vessels. The presence of small amounts of Neu5Gc was confirmed by MS. Absent any known alternate pathway for its synthesis, we reasoned that these small amounts of Neu5Gc might originate from exogenous sources. Indeed, human cells fed with Neu5Gc incorporated it into endogenous glycoproteins. When normal human volunteers ingested Neu5Gc, a portion was absorbed and eliminated in urine, and small quantities were incorporated into newly synthesized glycoproteins. Neu5Gc has never been reported in plants or microbes to our knowledge. We found that Neu5Gc is rare in poultry and fish, common in milk products, and enriched in red meats. Furthermore, normal humans have variable amounts of circulating IgA, IgM, and IgG antibodies against Neu5Gc, with the highest levels comparable to those of the previously known anti-alpha-galactose xenoreactive antibodies. This finding represents an instance wherein humans absorb and metabolically incorporate a nonhuman d…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NeuGc can be immunogenic in humans, who express a non-functional CMP-N-acetylneuraminic acid hydroxylase and have high levels of circulating anti-NeuGc antibodies.
“N-glycolylneuraminic (sialic) acid (NeuGc), can also be immunogenic in humans, who express a non-functional CMP-N-acetylneuraminic acid hydroxylase and as a result have high-levels of circulating anti-NeuGc antibodies [31,32].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [31]
Murine cells can produce α-gal and Neu5Gc at considerably higher levels than hamster cells, increasing the risks of immunogenicity.
“Murine cells can also produce α-gal and Neu5Gc at considerably higher levels than hamster cells, increasing the risks of immunogenicity (Tangvoranuntakul et al., 2003;Chung et al., 2008;Macher and Galili, 2008;Padler-Karavani et al., 2008;Ghaderi et al., 2012).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Tangvoranuntakul et al., 2003
Cites
Meat consumption and fatal ischemic heart disease
Snowdon, D. A., Phillips, R. L., & Fraser, G. E. (1984) · Preventive Medicine · doi:10.1016/0091-7435(84)90017-3 · Cited by 179 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Human milk oligosaccharides: Every baby needs a sugar mama
Bode, L. (2012) · Glycobiology · doi:10.1093/glycob/cws074 · Cited by 1,809 · see citing works
Mechanisms and consequences of intestinal dysbiosis
Weiss, G. A., & Hennet, T. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2509-x · Cited by 775 · see citing works
Cell culture processes for monoclonal antibody production
Li, F., Vijayasankaran, N., Shen, A. (., Kiss, R., & Amanullah, A. (2010) · mAbs · doi:10.4161/mabs.2.5.12720 · Cited by 739 · see citing works
Sialic acids in cancer biology and immunity
Pearce, O. M. T., & Läubli, H. (2016) · Glycobiology · doi:10.1093/glycob/cwv097 · Cited by 470 · see citing works
Liu, L. (2015) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.24444 · Cited by 428 · see citing works
Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins
Ghaderi, D., Taylor, R. E., Padler-Karavani, V., Diaz, S., & Varki, A. (2010) · Nature Biotechnology · doi:10.1038/nbt.1651 · Cited by 372 · see citing works
Self-citationGhaderi, D., Zhang, M., Hurtado-Ziola, N., & Varki, A. (2012) · Biotechnology and Genetic Engineering Reviews · doi:10.5661/bger-28-147 · Cited by 320 · see citing works
Self-citationTherapeutic glycoprotein production in mammalian cells
Lalonde, M.-E., & Durocher, Y. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.028 · Cited by 296 · see citing works
Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin
Byres, E., Paton, A. W., Paton, J. C., Löfling, J. C., Smith, D. F., Wilce, M. C. J., Talbot, U. M., Chong, D. C., Yu, H., Huang, S., et al. (2008) · Nature · doi:10.1038/nature07428 · Cited by 233 · see citing works
Self-citationGlycan analysis of therapeutic glycoproteins
Zhang, L., Luo, S., & Zhang, B. (2016) · mAbs · doi:10.1080/19420862.2015.1117719 · Cited by 207 · see citing works
Involvement of a Non-Human Sialic Acid in Human Cancer
Samraj, A. N., Läubli, H., Varki, N., & Varki, A. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00033 · Cited by 196 · see citing works
Self-citationMartin, M. J., Rayner, J. C., Gagneux, P., Barnwell, J. W., & Varki, A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503819102 · Cited by 193 · see citing works
Self-citationNANS-mediated synthesis of sialic acid is required for brain and skeletal development
van Karnebeek, C. D. M., Bonafé, L., Wen, X.-Y., Tarailo-Graovac, M., Balzano, S., Royer-Bertrand, B., Ashikov, A., Garavelli, L., Mammi, I., Turolla, L., et al. (2016) · Nature Genetics · doi:10.1038/ng.3578 · Cited by 164 · see citing works
Sweet escape: Sialic acids in tumor immune evasion
Büll, C., den Brok, M. H., & Adema, G. J. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.07.005 · Cited by 158 · see citing works
Alisson-Silva, F., Kawanishi, K., & Varki, A. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.07.002 · Cited by 156 · see citing works
Self-citationEvolutionary Glycomics: Characterization of Milk Oligosaccharides in Primates
Tao, N., Wu, S., Kim, J., An, H. J., Hinde, K., Power, M. L., Gagneux, P., German, J. B., & Lebrilla, C. B. (2011) · Journal of Proteome Research · doi:10.1021/pr1009367 · Cited by 132 · see citing works
Self-citationHost Adaptation of a Bacterial Toxin from the Human Pathogen Salmonella Typhi
Deng, L., Song, J., Gao, X., Wang, J., Yu, H., Chen, X., Varki, N., Naito-Matsui, Y., Galán, J. E., & Varki, A. (2014) · Cell · doi:10.1016/j.cell.2014.10.057 · Cited by 120 · see citing works
Self-citationKawanishi, K., Dhar, C., Do, R., Varki, N., Gordts, P. L. S. M., & Varki, A. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902902116 · Cited by 94 · see citing works
Self-citationSexual selection by female immunity against paternal antigens can fix loss of function alleles
Ghaderi, D., Springer, S. A., Ma, F., Cohen, M., Secrest, P., Taylor, R. E., Varki, A., & Gagneux, P. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102302108 · Cited by 79 · see citing works
Self-citationWang, Z., Burlak, C., Estrada, J. L., Li, P., Tector, M. F., & Tector, A. J. (2014) · Xenotransplantation · doi:10.1111/xen.12106 · Cited by 64 · see citing works
“Total IgG/IgM and anti-Neu5Gc IgG/IgM in human serum was measured by ELISA as described previously [15,16].”
MethodThe Possible Role of Anti-Neu5Gc as an Obstacle in Xenotransplantation
Tector, A. J., Mosser, M., Tector, M., & Bach, J.-M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00622 · Cited by 60 · see citing works
Wahrenbrock, M. G., & Varki, A. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3851 · Cited by 58 · see citing works
Self-citationJayo, R. G., Thaysen-Andersen, M., Lindenburg, P. W., Haselberg, R., Hankemeier, T., Ramautar, R., & Chen, D. D. Y. (2014) · Analytical Chemistry · doi:10.1021/ac5010212 · Cited by 54 · see citing works
Glycoengineering Chinese hamster ovary cells: a short history
Donini, R., Haslam, S. M., & Kontoravdi, C. (2021) · Biochemical Society Transactions · doi:10.1042/bst20200840 · Cited by 37 · see citing works
- Authors
- Tangvoranuntakul, P., Gagneux, P., Diaz, S., Bardor, M., Varki, N., Varki, A., & Muchmore, E.
- Affiliations
- University of California San Diego (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-10
- Volume
- 100
- Issue
- 21
- Pages
- 12045-12050
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC218710
- OpenAlex
- W2136482421
- Cited by
- 625
- References
- 1
- Citations by year
- 2026: 25 · 2025: 30 · 2024: 21 · 2023: 27 · 2022: 28 · 2021: 30 · 2020: 41 · 2019: 35 · 2018: 33 · 2017: 29 · 2016: 38 · 2015: 29 · 2014: 38 · 2013: 36 · 2012: 36
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM032373, R01-GM323373)
- National Center for Research Resources (M-01RR00827, M01RR000827)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
- Keywords
- N-glycolylneuraminic acid, sialic acid, xenoreactive antibodies, anti-Neu5Gc antibodies, secretory epithelia, breast cancer, red meat, dairy products, autoantibodies
- MeSH terms
- Animals, Antibodies, Antibody Specificity, Biological Transport, Active, Dietary Carbohydrates, Fetus, Glycoproteins, Humans, Neoplasms, Neuraminic Acids, Mass Spectrometry, Caco-2 Cells
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 ›
Are you an author, or do you see a problem with this page? Request a review
