Evidence map›Paper›PMID 19828701›Full record

ArticleBlood2009

Evidence for a novel human-specific xeno-auto-antibody response against vascular endothelium.

Tho Pham, Christopher J Gregg, Felix Karp, Renee Chow, Vered Padler-Karavani, Hongzhi Cao, Xi Chen, Joseph L Witztum, Nissi M Varki, Ajit Varki

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 118 citations in OpenAlex.

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16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Tho PhamGlycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093-0687, USA.
Christopher J Gregg
Felix Karp
Renee Chow
Vered Padler-Karavani
Hongzhi Cao
Xi Chen
Joseph L Witztum
Nissi M Varki
Ajit Varki
University of California, San Diego · USUniversity of California, Davis · US

Funding

BIOSYNTHESIS AND REGULATION OF SUBSTITUTED SIALIC ACIDSR01GM032373 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VARKI, AJIT P · 1985 to 2022
$6.9M
SULFATED OLIGOSACCHARIDES OF NORMAL AND MALIGNANT CELLSR01CA038701 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VARKI, AJIT P · 1985 to 2015
$5.5M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA038701NCI NIH HHS R01-CA38701NIGMS NIH HHS R01 GM032373NIGMS NIH HHS R01-GM32373
6 · The paper itself

Abstract

Humans are genetically unable to synthesize the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc). However, Neu5Gc can be metabolically incorporated and covalently expressed on cultured human cell surfaces. Meanwhile, humans express varying and sometimes high titers of polyclonal anti-Neu5Gc antibodies. Here, a survey of human tissues by immunohistochemistry with both a monospecific chicken anti-Neu5Gc antibody and with affinity-purified human anti-Neu5Gc antibodies demonstrates endothelial expression of Neu5Gc, likely originating from Neu5Gc-rich foods like red meats. We hypothesized that the combination of Neu5Gc incorporation and anti-Neu5Gc antibodies can induce endothelial activation. Indeed, the incubation of high-titer human sera with Neu5Gc-fed endothelial cells led to Neu5Gc-dependent antibody binding, complement deposition, endothelial activation, selectin expression, increased cytokine secretion, and monocyte binding. The proinflammatory cytokine tumor necrosis factor-alpha also selectively enhanced human anti-Neu5Gc antibody reactivity. Anti-Neu5Gc antibodies affinity-purified from human serum also directed Neu5Gc-dependent complement deposition onto cultured endothelial cells. These data indicate a novel human-specific mechanism in which Neu5Gc-rich foods deliver immunogenic Neu5Gc to the endothelium, giving anti-Neu5Gc antibody- and complement-dependent activation, and potentially contributing to human vascular pathologies. In the case of atherosclerosis, Neu5Gc is present both in endothelium overlying plaques and in subendothelial regions, providing multiple pathways for accelerating inflammation in this disease.

Indexed as

AnimalsAntibodiesAtherosclerosisBinding, CompetitiveBlood VesselsCell LineCells, CulturedChickensColonEndothelium, VascularFemaleFlow CytometryHumansImmunohistochemistryMalePlacentaAntibodiesN-(O-acetyl)glycoloylneuraminic acidSialic AcidsTumor Necrosis Factor-alpha

Identifiers

PMID19828701
PMCPMC2792214
OpenAlexW2053436608

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.