Evidence map›Paper›PMID 25098831›Full record

Trial reportPloS one2014

Upregulation of immunoproteasome subunits in myositis indicates active inflammation with involvement of antigen presenting cells, CD8 T-cells and IFNΓ.

Khetam Ghannam, Lorena Martinez-Gamboa, Lydia Spengler, Sabine Krause, Biljana Smiljanovic, Marc Bonin, Salyan Bhattarai, Andreas Grützkau, Gerd-R Burmester, Thomas Häupl and 1 more

Open access · goldAbstract readClinical TrialComparative Study
In one paragraph

Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.4field-weighted citation impact, top 12% 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, 45 citations in OpenAlex.

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  19. The ubiquitin proteasome system as a potential therapeutic target for systemic sclerosis.Translational research : the journal of laboratory and clinical medicine · 2018
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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

11 authors at 2 institutions in 1 country.

Khetam GhannamDepartment of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
Lorena Martinez-GamboaDepartment of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
Lydia SpenglerDepartment of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
Sabine KrauseFriedrich Baur Institute, Ludwig Maximilians University, Munich, Germany.
Biljana SmiljanovicDepartment of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
Marc BoninDepartment of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
Salyan BhattaraiDepartment of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
Andreas GrützkauGerman Arthritis Research Center, Berlin, Germany.
Gerd-R BurmesterDepartment of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
Thomas HäuplDepartment of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
Eugen FeistDepartment of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
Charité - Universitätsmedizin Berlin · DELudwig-Maximilians-Universität München · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveIn idiopathic inflammatory myopathies (IIM) infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. To decipher the role of immunoproteasomes in myositis, we investigated individual cell types and muscle tissues and focused on possible immune triggers.

methodsExpression of constitutive (PSMB5, -6, -7) and corresponding immunoproteasomal subunits (PSMB8, -9, -10) was analyzed by real-time RT-PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM) and healthy donors (HD). Protein analysis in muscle biopsies was performed by western blot. Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses.

resultsReal-time RT-PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8/-9/-10) in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were elevated in IIM compared to NIM and exceeded levels of matched blood samples. Proteins of PSMB8 and -9 were found only in IIM but not NIM muscle biopsies. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed these results and revealed involvement of the antigen processing and presentation pathway. Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1, IRF1 and IFNγ expression. Elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood.

conclusionsImmunoproteasomes seem to indicate IIM activity and suggest that dominant involvement of antigen processing and presentation may qualify these diseases exemplarily for the evolving therapeutic concepts of immunoproteasome specific inhibition.

Indexed as

AdultAgedCD8-Positive T-LymphocytesDendritic CellsFemaleGene Expression Regulation, EnzymologicHumansInterferon-gammaInterferon Regulatory Factor-1MaleMiddle AgedMuscle ProteinsMyositisProteasome Endopeptidase ComplexSTAT1 Transcription FactorUp-RegulationIFNG protein, humanInterferon-gammaInterferon Regulatory Factor-1IRF1 protein, humanMuscle ProteinsProteasome Endopeptidase ComplexSTAT1 protein, humanSTAT1 Transcription Factor

Identifiers

PMID25098831
PMCPMC4123911
OpenAlexW2058748752

What OpenQuestion holds

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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.