Evidence map›Paper›PMID 26068105›Full record

ArticlePloS one2015

The MS Risk Allele of CD40 Is Associated with Reduced Cell-Membrane Bound Expression in Antigen Presenting Cells: Implications for Gene Function.

Judith Field, Fernando Shahijanian, Stephen Schibeci, Australia and New Zealand MS Genetics Consortium (ANZgene), Laura Johnson, Melissa Gresle, Louise Laverick, Grant Parnell, Graeme Stewart, Fiona McKay and 3 more

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

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

21 citing papers in PubMed, 48 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

13 authors at 4 institutions in 1 country.

Judith FieldMultiple Sclerosis Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria., Australia.
Fernando ShahijanianCentre for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
Stephen SchibeciCentre for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
Australia and New Zealand MS Genetics Consortium (ANZgene)
Laura JohnsonMultiple Sclerosis Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria., Australia.
Melissa GresleMelbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
Louise LaverickMelbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
Grant ParnellCentre for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
Graeme StewartCentre for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
Fiona McKayCentre for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
Trevor KilpatrickMultiple Sclerosis Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria., Australia; Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; Melbourne Neuroscience Institute, University of Melbourne, Melbourne, Victoria, Australia.
Helmut ButzkuevenMelbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
David BoothCentre for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
University of Sydney · AUThe Royal Melbourne Hospital · AUFlorey Institute of Neuroscience and Mental Health · AUUniversity of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human genetic and animal studies have implicated the costimulatory molecule CD40 in the development of multiple sclerosis (MS). We investigated the cell specific gene and protein expression variation controlled by the CD40 genetic variant(s) associated with MS, i.e. the T-allele at rs1883832. Previously we had shown that the risk allele is expressed at a lower level in whole blood, especially in people with MS. Here, we have defined the immune cell subsets responsible for genotype and disease effects on CD40 expression at the mRNA and protein level. In cell subsets in which CD40 is most highly expressed, B lymphocytes and dendritic cells, the MS-associated risk variant is associated with reduced CD40 cell-surface protein expression. In monocytes and dendritic cells, the risk allele additionally reduces the ratio of expression of full-length versus truncated CD40 mRNA, the latter encoding secreted CD40. We additionally show that MS patients, regardless of genotype, express significantly lower levels of CD40 cell-surface protein compared to unaffected controls in B lymphocytes. Thus, both genotype-dependent and independent down-regulation of cell-surface CD40 is a feature of MS. Lower expression of a co-stimulator of T cell activation, CD40, is therefore associated with increased MS risk despite the same CD40 variant being associated with reduced risk of other inflammatory autoimmune diseases. Our results highlight the complexity and likely individuality of autoimmune pathogenesis, and could be consistent with antiviral and/or immunoregulatory functions of CD40 playing an important role in protection from MS.

Indexed as

AdolescentAdultAgedAllelesB-LymphocytesCD40 AntigensCell MembraneCohort StudiesDendritic CellsDown-RegulationFemaleGenotypeHumansLymphocyte ActivationMaleMiddle AgedCD40 AntigensRNA, Messenger

Identifiers

PMID26068105
PMCPMC4465929
OpenAlexW2101945011

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.