Evidence map›Paper›PMID 39529136›Full record

ArticleArthritis research & therapy2024

Neutrophil and mononuclear leukocyte pathways and upstream regulators revealed by serum proteomics of adult and juvenile dermatomyositis.

A Clare Sparling, James M Ward, Kakali Sarkar, Adam Schiffenbauer, Payam Noroozi Farhadi, Michael A Smith, Saifur Rahman, Kamelia Zerrouki, Frederick W Miller, Jian-Liang Li and 2 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00017914 (Studies in the Natural History and Pathogenesis of Childhood-Onset and Adult-Onset Idiopathic Inflammatory Myopathies), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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.

NCT00017914 recruitingnot on this map

Studies in the Natural History and Pathogenesis of Childhood-Onset and Adult-Onset Idiopathic Inflammatory Myopathies

TypeobservationalSponsorNational Institute of Environmental Health Sciences (NIEHS)Ran1995Enrolled1,200ConditionsDermatomyositis, Polymyositis, Inclusion Body Myositis
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

12 authors.

A Clare SparlingEnvironmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Building 10, CRC Rm 6-5700, MSC 1301 10 Center Drive, Bethesda, MD, 20892-1301, USA.ORCID 0009-0001-1807-0221
James M WardIntegrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA.ORCID 0000-0002-9510-2848
Kakali SarkarEnvironmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Building 10, CRC Rm 6-5700, MSC 1301 10 Center Drive, Bethesda, MD, 20892-1301, USA.
Adam SchiffenbauerEnvironmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Building 10, CRC Rm 6-5700, MSC 1301 10 Center Drive, Bethesda, MD, 20892-1301, USA.
Payam Noroozi FarhadiEnvironmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Building 10, CRC Rm 6-5700, MSC 1301 10 Center Drive, Bethesda, MD, 20892-1301, USA.ORCID 0000-0003-2419-050X
Michael A SmithBioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Saifur RahmanBioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Kamelia ZerroukiBioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Frederick W MillerIntegrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA.ORCID 0000-0003-2831-9593
Jian-Liang LiIntegrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA.
Kerry A CaseyBioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Lisa G RiderEnvironmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Building 10, CRC Rm 6-5700, MSC 1301 10 Center Drive, Bethesda, MD, 20892-1301, USA. riderl@mail.nih.gov.ORCID 0000-0002-6912-2458

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesSerum protein abundance was assessed in adult and juvenile dermatomyositis (DM and JDM) patients to determine differentially regulated proteins, altered pathways, and candidate disease activity biomarkers.

methodsSerum protein expression from 17 active adult DM and JDM patients each was compared to matched, healthy control subjects by a multiplex immunoassay. Pathway analysis and protein clustering of the differentially regulated proteins were examined to assess underlying mechanisms. Candidate disease activity biomarkers were identified by correlating protein expression with disease activity measures.

resultsSeventy-eight of 172 proteins were differentially expressed in the sera of DM and JDM patients compared to healthy controls. Forty-eight proteins were differentially expressed in DM, 32 proteins in JDM, and 14 proteins in both DM and JDM. Twelve additional differentially expressed proteins were identified after combining the DM and JDM cohorts. C-X-C motif chemokine ligand 10 (CXCL10) was the most strongly upregulated protein in both DM and JDM sera. Other highly upregulated proteins in DM included S100 calcium binding protein A12 (S100A12), CXCL9, and nicotinamide phosphoribosyltransferase (NAMPT), while highly upregulated proteins in JDM included matrix metallopeptidase 3 (MMP3), growth differentiation factor 15 (GDF15), and von Willebrand factor (vWF). Pathway analysis indicated that phosphoinositide 3-kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), and toll-like receptor 7 (TLR7) signaling were activated in DM and JDM. Additional pathways specific to DM or JDM were identified. A protein cluster associated with neutrophils and mononuclear leukocytes and a cluster of interferon-associated proteins were observed in both DM and JDM. Twenty-two proteins in DM and 24 proteins in JDM sera correlated with global, muscle, and/or skin disease activity. Seven proteins correlated with disease activity measures in both DM and JDM sera. IL-1 receptor like 1 (IL1RL1) emerged as a candidate global disease activity biomarker in DM and JDM.

conclusionCoordinate analysis of protein expression in DM and JDM patient sera by a multiplex immunoassay validated previous gene expression studies and identified novel dysregulated proteins, altered signaling pathways, and candidate disease activity biomarkers. These findings may further inform the assessment of DM and JDM patients and aid in the identification of potential therapeutic targets.

Indexed as

BiomarkersDermatomyositisLeukocytes, MononuclearNeutrophilsProteomicsAdolescentAdultAgedBlood ProteinsChildFemaleHumansMaleMiddle AgedSignal TransductionYoung AdultBiomarkersBlood ProteinsBiomarkersDermatomyositisDisease activityJuvenile dermatomyositisMonocytesMultiplex proteomicsNeutrophils

Identifiers

PMID39529136
PMCPMC11552237

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Registered trials

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.