Evidence map›Paper›PMID 29371615›Full record

ArticleScientific reports2018

Retinoic acid prevents immunogenicity of milk lipocalin Bos d 5 through binding to its immunodominant T-cell epitope.

Karin Hufnagl, Debajyoti Ghosh, Stefanie Wagner, Alessandro Fiocchi, Lamia Dahdah, Rodolfo Bianchini, Nina Braun, Ralf Steinborn, Martin Hofer, Marion Blaschitz and 5 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.3field-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

28 citing papers in PubMed, 55 citations in OpenAlex.

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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

15 authors at 6 institutions in 4 countries.

Karin HufnaglThe Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Debajyoti GhoshUniversity of Cincinnati College of Medicine, Ohio, USA.
Stefanie WagnerThe Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Alessandro FiocchiChildrens Hospital Bambino Gesù, Rome, Italy.
Lamia DahdahChildrens Hospital Bambino Gesù, Rome, Italy.
Rodolfo BianchiniThe Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Nina BraunThe Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Ralf SteinbornGenomics Core Facility, VetCore, University of Veterinary Medicine, Vienna, Austria.
Martin HoferGenomics Core Facility, VetCore, University of Veterinary Medicine, Vienna, Austria.
Marion BlaschitzCenter for Anthropogenic Infections, Division for Public Health, Austrian Agency for Health and Food Safety, Vienna, Austria.
Georg A RothDepartment of Anesthesiology, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria; RAIC Laboratory 13C1, Medical University of Vienna, Vienna, Austria.
Gerlinde HofstetterThe Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Franziska Roth-WalterThe Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Luis F PaciosDepartment of Natural Systems and Resources, ETSI Montes, Technical University of Madrid, and Centro de Biotecnología y Genómica de Plantas (CBGP) UPM-INIA, Campus de Montegancedo UPM, Madrid, Spain.ORCID http://orcid.org/0000-0002-0585-4289
Erika Jensen-JarolimThe Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria. erika.jensen-jarolim@meduniwien.ac.at.
University of Veterinary Medicine Vienna · ATBambino Gesù Children's Hospital · ITAustrian Agency for Health and Food Safety · ATCentre for Plant Biotechnology and Genomics · ESMedical University of Vienna · ATUniversity of Cincinnati Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The major cow's milk allergen Bos d 5 belongs to the lipocalin protein family, with an intramolecular pocket for hydrophobic ligands. We investigated whether Bos d 5 when loaded with the active vitamin A metabolite retinoic acid (RA), would elicit differential immune responses compared to the unloaded state. By in silico docking an affinity energy of -7.8 kcal/mol was calculated for RA into Bos d 5. Loading of RA to Bos d 5 could be achieved in vitro, as demonstrated by ANS displacement assay, but had no effect on serum IgE binding in tolerant or challenge-positive milk allergic children. Bioinformatic analysis revealed that RA binds to the immunodominant T-cell epitope region of Bos d 5. In accordance, Bos d 5 significantly suppressed the CD3+ CD4+ cell numbers, proliferative response and IL-10, IL-13 and IFN-γ secretion from stimulated human PBMCs only when complexed with RA. This phenomenon was neither associated with apoptosis of T-cells nor with the activation of Foxp3+ T-cells, but correlated likely with enhanced stability to lysosomal digestion due to a predicted overlap of Cathepsin S cleavage sites with the RA binding site. Taken together, proper loading of Bos d 5 with RA may suppress its immunogenicity and prevent its allergenicity.

Indexed as

AllergensAnimalsCattleCell ProliferationEpitopes, T-LymphocyteHumansImmunoglobulin EImmunologic FactorsInterferon-gammaInterleukin-10Interleukin-13Leukocytes, MononuclearLipocalinsLysosomesMolecular Docking SimulationProtein BindingAllergensBos d 5 allergen, Bos taurusEpitopes, T-LymphocyteIL10 protein, humanImmunoglobulin EImmunologic FactorsInterferon-gammaInterleukin-10Interleukin-13LipocalinsTretinoin

Identifiers

PMID29371615
PMCPMC5785490
OpenAlexW2799679445

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.