Evidence map›Paper›PMID 22332874›Full record

Trial reportPediatric diabetes2012

Expansion of CD4+CD25+FOXP3+ regulatory T cells in infants of mothers with type 1 diabetes.

Kristiina Luopajärvi, Janne K Nieminen, Jorma Ilonen, Hans K Akerblom, Mikael Knip, Outi Vaarala

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Pediatric diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 26% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Early life origin of type 1 diabetes.Seminars in immunopathology · 2017
    Review
  8. Article
  9. 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

6 authors at 4 institutions in 2 countries.

Kristiina LuopajärviImmune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland. kristiina.luopajarvi@thl.fi
Janne K Nieminen
Jorma Ilonen
Hans K Akerblom
Mikael Knip
Outi Vaarala
National Institutes of Health · USFolkhälsans Forskningscentrum · FIHelsinki University Hospital · FIUniversity of Eastern Finland · FI

Funding

Trial to Reduce IDDM in the Genetically at Risk StudyU01HD040364 · NICHD · UNIVERSITY OF HELSINKI · PI KNIP, MIKAEL · 2001 to 2015
$32.7M
NICHD NIH HHS U01 HD040364
6 · The paper itself

Abstract

backgroundReduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers.

objectiveTo evaluate the hypothesis that exposure of the offspring to maternal insulin therapy induces regulatory mechanisms in utero, we compared the FOXP3 expressing regulatory T cells in cord blood (CB) of infants born to mothers with or without T1D. SUBJECTS AND

methodsCord blood mononuclear cells (CBMCs) from 20 infants with maternal T1D and from 20 infants with an unaffected mother were analyzed for the numbers of CD4+CD25+FOXP3+ cells ex vivo and after in vitro stimulation with human insulin by flow cytometry. The mRNA expression of FOXP3, NFATc2, STIM1, interleukin (IL)-10, and transforming growth factor (TGF)-β was measured by real-time reverse transcription polymerase chain reaction.

resultsThe percentage of FOXP3+ cells in CD4+CD25(high) cells was higher in the CB of the infants with maternal T1D when compared with the infants of unaffected mothers (p = 0.023). After in vitro insulin stimulation an increase in the percentage of FOXP3+ cells in CD4+CD25(high) cells (p = 0.0002) as well as upregulation of FOXP3, NFATc2, STIM1, IL-10, and TGF-β transcripts in CBMCs (p < 0.013 for all; Wilcoxon test) was observed only in the offspring of mothers with T1D, in whom the disease-related PTPN22 allele was associated with reduced STIM1 and NFATc2 response in insulin-stimulated CBMCs (p = 0.007 and p = 0.014).

conclusionsWe suggest that maternal insulin treatment induces expansion of regulatory T cells in the fetus, which might contribute to the lower risk of diabetes in children with maternal vs. paternal diabetes.

Indexed as

CD4 AntigensDiabetes Mellitus, Type 1FemaleFetal BloodForkhead Transcription FactorsHumansInfantInfant, NewbornInsulinInterleukin-2 Receptor alpha SubunitMaleMothersT-Lymphocytes, RegulatoryCD4 AntigensForkhead Transcription FactorsFOXP3 protein, humanIL2RA protein, humanInsulinInterleukin-2 Receptor alpha Subunit

Identifiers

PMID22332874
PMCPMC4225542
OpenAlexW2122309614

What OpenQuestion holds

Textmetadata
LicenceTDM
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.