Evidence map›Paper›PMID 34034363›Full record

ArticleImmunity, inflammation and disease2021

Tick salivary gland extract induces alpha-gal syndrome in alpha-gal deficient mice.

Shailesh K Choudhary, Shahid Karim, Onyinye I Iweala, Shivangi Choudhary, Gary Crispell, Surendra Raj Sharma, Claire T Addison, Mike Kulis, Brian H Herrin, Susan E Little and 1 more

Open access · goldAbstract read
In one paragraph

Article in Immunity, inflammation and disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

32 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Differential alpha-gal expression duringThe journal of allergy and clinical immunology. Global · 2026
    Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Pre-clinical strategies and emerging technologies driving advances in the alpha-gal syndrome.Allergology international : official journal of the Japanese Society of Allergology · 2025
    Review
  10. Is Zebrafish a Good Model for the Alpha-Gal Syndrome?FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4.The Journal of allergy and clinical immunology · 2024
    Article
  17. Article
  18. The role of glycosylation in clinical allergy and immunology.The Journal of allergy and clinical immunology · 2024
    Review
  19. Article
  20. Article
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

11 authors at 3 institutions in 1 country.

Shailesh K ChoudharyDivision of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.ORCID 0000-0002-8160-6711
Shahid KarimCenter for Molecular and Cellular Biosciences, Department of Cell and Molecular Biology, School of Biological, Environmental, and Earth Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi, USA.
Onyinye I IwealaDivision of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Shivangi ChoudharyDivision of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Gary CrispellCenter for Molecular and Cellular Biosciences, Department of Cell and Molecular Biology, School of Biological, Environmental, and Earth Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi, USA.
Surendra Raj SharmaCenter for Molecular and Cellular Biosciences, Department of Cell and Molecular Biology, School of Biological, Environmental, and Earth Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi, USA.
Claire T AddisonDivision of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Mike KulisUNC Food Allergy Initiative, Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, USA.
Brian H HerrinDepartment of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, Kansas, USA.
Susan E LittleDepartment of Veterinary Pathobiology, Oklahoma State University, Stillwater, Oklahoma, USA.
Scott P ComminsDivision of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.ORCID 0000-0003-1198-2428
University of North Carolina at Chapel Hill · USOklahoma State University · USUniversity of Southern Mississippi · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Training and Mentoring Core P20GM103476 · NIGMS · UNIVERSITY OF SOUTHERN MISSISSIPPI · PI MICHAEL R GARRETT · 2012 to 2026
$60.2M
TOUGALOO PROTEOMICSP20RR016476 · NCRR · UNIVERSITY OF SOUTHERN MISSISSIPPI · PI SHEARER, GLEN · 2001 to 2011
$30.4M
Understanding alpha-gal red meat allergyR01AI135049 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Scott Palmer Commins · 2018 to 2026
$5.1M
Delayed Anaphylaxis to Mammalian Meat caused by IgE Ab to alpha-galR56AI113095 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COMMINS, SCOTT PALMER · 2014 to 2014
$390k
NCI NIH HHS P30 CA016086NCRR NIH HHS P20 RR016476NIAID NIH HHS R01 AI135049NIAID NIH HHS R56 AI113095NIGMS NIH HHS P20 GM103476
6 · The paper itself

Abstract

introductionAlpha-gal syndrome (AGS) is characterized by delayed hypersensitivity to non-primate mammalian meat in people having specific immunoglobulin E (sIgE) to the oligosaccharide galactose-alpha-1,3-galactose. AGS has been linked to tick bites from Amblyomma americanum (Aa) in the U.S. A small animal model of meat allergy is needed to study the mechanism of alpha-gal sensitization, the effector phase leading to delayed allergic responses and potential therapeutics to treat AGS.

methodsEight- to ten-weeks old mice with a targeted inactivation of alpha-1,3-galactosyltransferase (AGKO) were injected intradermally with 50 μg of Aa tick salivary gland extract (TSGE) on days 0, 7, 21, 28, 42, and 49. Total IgE and alpha-gal sIgE were quantitated on Day 56 by enzyme-linked immunosorbent assay. Mice were challenged orally with 400 mg of cooked pork kidney homogenate or pork fat. Reaction severity was assessed by measuring a drop in core body temperature and scoring allergic signs.

resultsCompared to control animals, mice treated with TSGE had 190-fold higher total IgE on Day 56 (0.60 ± 0.12 ng/ml vs. 113.2 ± 24.77 ng/ml; p < 0.001). Alpha-gal sIgE was also produced in AGKO mice following TSGE sensitization (undetected vs. 158.4 ± 72.43 pg/ml). Further, sensitized mice displayed moderate clinical allergic signs along with a drop in core body temperature of ≥2°C as an objective measure of a systemic allergic reaction. Interestingly, female mice had higher total IgE responses to TSGE treatment but male mice had larger declines in mean body temperature.

conclusionTSGE-sensitized AGKO mice generate sIgE to alpha-gal and demonstrate characteristic allergic responses to pork fat and pork kidney. In keeping with the AGS responses documented in humans, mice reacted more rapidly to organ meat than to high fat pork challenge. This mouse model establishes the central role of tick bites in the development of AGS and provides a small animal model to mechanistically study mammalian meat allergy.

Indexed as

Food HypersensitivityTicksAnimalsFemaleMaleMicePlant ExtractsSalivary GlandsPlant Extractsalpha-galalpha-gal knockout micealpha-gal syndromeAmblyomma americanumdelayed allergic responsesfood allergymammalian meattick

Identifiers

PMID34034363
PMCPMC8342229
OpenAlexW3165866951

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.