Evidence map›Paper›PMID 23171592›Full record

ArticleBMC medical genomics2012

Genomic signatures characterize leukocyte infiltration in myositis muscles.

Wei Zhu, Katie Streicher, Nan Shen, Brandon W Higgs, Chris Morehouse, Lydia Greenlees, Anthony A Amato, Koustubh Ranade, Laura Richman, David Fiorentino and 3 more

Open access · goldAbstract read
In one paragraph

Article in BMC medical genomics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 pooled it
1.6field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Serum-Circulating microRNAs in Sporadic Inclusion Body Myositis.International journal of molecular sciences · 2023
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  13. Article
  14. Article
  15. Article
  16. Article
  17. [Advances in epigenetic markers of dermatomyositis/polymyositis].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2019
    Article
  18. 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

13 authors at 3 institutions in 2 countries.

Wei ZhuTranslational Sciences, MedImmune, LLC, Gaithersburg, MD 20878, USA. ZhuW@medimmune.com
Katie Streicher
Nan Shen
Brandon W Higgs
Chris Morehouse
Lydia Greenlees
Anthony A Amato
Koustubh Ranade
Laura Richman
David Fiorentino
Bahija Jallal
Steven A Greenberg
Yihong Yao
Brigham and Women's Hospital · USRenji Hospital · CNStanford University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLeukocyte infiltration plays an important role in the pathogenesis and progression of myositis, and is highly associated with disease severity. Currently, there is a lack of: efficacious therapies for myositis; understanding of the molecular features important for disease pathogenesis; and potential molecular biomarkers for characterizing inflammatory myopathies to aid in clinical development.

methodsIn this study, we developed a simple model and predicted that 1) leukocyte-specific transcripts (including both protein-coding transcripts and microRNAs) should be coherently overexpressed in myositis muscle and 2) the level of over-expression of these transcripts should be correlated with leukocyte infiltration. We applied this model to assess immune cell infiltration in myositis by examining mRNA and microRNA (miRNA) expression profiles in muscle biopsies from 31 myositis patients and 5 normal controls.

resultsSeveral gene signatures, including a leukocyte index, type 1 interferon (IFN), MHC class I, and immunoglobulin signature, were developed to characterize myositis patients at the molecular level. The leukocyte index, consisting of genes predominantly associated with immune function, displayed strong concordance with pathological assessment of immune cell infiltration. This leukocyte index was subsequently utilized to differentiate transcriptional changes due to leukocyte infiltration from other alterations in myositis muscle. Results from this differentiation revealed biologically relevant differences in the relationship between the type 1 IFN pathway, miR-146a, and leukocyte infiltration within various myositis subtypes.

conclusionsResults indicate that a likely interaction between miR-146a expression and the type 1 IFN pathway is confounded by the level of leukocyte infiltration into muscle tissue. Although the role of miR-146a in myositis remains uncertain, our results highlight the potential benefit of deconvoluting the source of transcriptional changes in myositis muscle or other heterogeneous tissue samples. Taken together, the leukocyte index and other gene signatures developed in this study may be potential molecular biomarkers to help to further characterize inflammatory myopathies and aid in clinical development. These hypotheses need to be confirmed in separate and sufficiently powered clinical trials.

Indexed as

Gene Expression ProfilingGenomicsAdultAgedAged, 80 and overAnimalsCase-Control StudiesCell MovementCluster AnalysisDown-RegulationGenome, HumanHumansInterferon Type ILeukocytesMiceMicroRNAsInterferon Type IMicroRNAsRNA, Messenger

Identifiers

PMID23171592
PMCPMC3541209
OpenAlexW2107297770

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.