Evidence map›Paper›PMID 35091341›Full record

ArticleEBioMedicine2022

Immune response to a conserved enteroviral epitope of the major capsid VP1 protein is associated with lower risk of cardiovascular disease.

Nadežda Pupina, Annela Avarlaid, Helle Sadam, Arno Pihlak, Mariliis Jaago, Jürgen Tuvikene, Annika Rähni, Anu Planken, Margus Planken, Eija Kalso and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 36% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. 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

19 authors at 4 institutions in 2 countries.

Nadežda PupinaProtobios LLC, Mäealuse 4, Tallinn 12618, Estonia.
Annela AvarlaidDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Estonia.
Helle SadamProtobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia.
Arno PihlakProtobios LLC, Mäealuse 4, Tallinn 12618, Estonia.
Mariliis JaagoProtobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia.
Jürgen TuvikeneProtobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia; dxlabs LLC, Mäealuse 4, Tallinn 12618, Estonia.
Annika RähniProtobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia.
Anu PlankenThe North Estonia Medical Center, Tallinn, Estonia.
Margus PlankenThe North Estonia Medical Center, Tallinn, Estonia.
Eija KalsoDepartment of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University Hospital and Department of Pharmacology and SleepWell Research Programme, University of Helsinki, Finland.
Pentti J TienariDepartment of Neurology, Neurocenter, Helsinki University Hospital, and Translational Immunology Research Program, University of Helsinki, Finland.
Janne K NieminenDepartment of Neurology, Neurocenter, Helsinki University Hospital, and Translational Immunology Research Program, University of Helsinki, Finland.
Mikko R J SeppänenDepartment of Neurology, Neurocenter, Helsinki University Hospital, and Translational Immunology Research Program, University of Helsinki, Finland.
Antti VaheriDepartment of Virology, Medicum, University of Helsinki, Finland.
Dan LindholmDepartment of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
Juha SinisaloHeart and Lung Center, Helsinki University Hospital, University of Helsinki, Finland.
Pirkko PussinenOral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Finland.
Tõnis TimmuskProtobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia.
Kaia PalmProtobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia. Electronic address: kaia@protobios.com.
University of Helsinki · FITallinn University of Technology · EENorth Estonia Medical Centre · EEProtobios (Estonia) · EE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMajor cardiac events including myocardial infarction (MI) are associated with viral infections. However, how specific infections contribute to the cardiovascular insults has remained largely unclear.

methodsWe employed next generation phage display mimotope-variation analysis (MVA) to explore the link between antibody-based immune response and severe cardiovascular conditions. Here, we used a case-control design, including the first-stage discovery cohort (n = 100), along with cohorts for second-stage discovery (n = 329) and validation (n = 466).

findingsWe observed strong antibody response to the peptide antigens with Gly-Ile-X-Asp (G-I-X-D) core structure in healthy individuals but not in patients with MI. Analysis of the origin of this epitope linked it with the N-terminus of the VP1 protein of poliovirus 3 (PV3), but also other species of picornaviruses. Consistently, we found low levels of antibody response to the G-I-X-D epitope in individuals with severe cardiac disease complications.

interpretationOur findings imply that antibody response to the G-I-X-D epitope is associated with polio vaccinations and that high antibody levels to this epitope could discriminate healthy individuals from prospective MI patients as a blood-derived biomarker. Together, these findings highlight the importance of epitope-specific antibody response and suggest that protective immunity against the polio- and non-polio enteroviral infections support improved cardiovascular health.

fundingEstonian Ministry of Education (5.1-4/20/170), Estonian Research Council (PRG573, PRG805), H2020-MSCA-RISE-2016 (EU734791), H2020 PANBioRA (EU760921), European Union through the European Regional Development Fund (Project no. 2014-2020.4.01.15-0012), Helsinki University Hospital grants, Mary and Georg C. Ehrnrooth Foundation, Finnish Eye Foundation, Finska Läkaresällskapet, The Finnish Society of Sciences and Letters, Magnus Ehrnrooth Foundation and Sigrid Jusélius Foundation.

Indexed as

Cardiovascular DiseasesPoliovirusCapsidCapsid ProteinsEpitopesHumansImmunityProspective StudiesCapsid ProteinsEpitopesAntibodiesCardiovascular diseasesEnterovirusesEpitopeMyocardial infarctionPoliovirus

Identifiers

PMID35091341
PMCPMC8801986
OpenAlexW4206963082

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.