Evidence map›Paper›PMID 40915939›Full record

ArticleAnnals of the rheumatic diseases2025

Discovery of tissue-specific proteomic signatures in juvenile dermatomyositis highlights pathways reflecting persistent disease activity, clinical heterogeneity, and myositis-specific autoantibody subtype.

Jessica Neely, Sara E Sabbagh, Jeffrey Dvergsten, Chioma Madubata, Celine C Berthier, Zilan Zheng, Christine Goudsmit, Sophia Matossian, Sean P Ferris, Gabriela K Fragiadakis and 5 more

Abstract read
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In one paragraph

Article in Annals of the rheumatic diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

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

3 citing papers in PubMed.

  1. Review
  2. Review
  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

15 authors.

Jessica NeelyDepartment of Pediatrics, Division of Rheumatology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: Jessica.Neely@ucsf.edu.
Sara E SabbaghDepartment of Pediatrics, Division of Rheumatology, The Medical College of Wisconsin, Milwaukee, WI, USA.
Jeffrey DvergstenDepartment of Pediatrics, Division of Rheumatology, Duke University, Durham, NC, USA.
Chioma MadubataDepartment of Pediatrics, Division of Rheumatology, University of California, San Francisco, San Francisco, CA, USA.
Celine C BerthierDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
Zilan ZhengDepartment of Pediatrics, Division of Rheumatology, University of California, San Francisco, San Francisco, CA, USA.
Christine GoudsmitDepartment of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
Sophia MatossianDepartment of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
Sean P FerrisDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Gabriela K FragiadakisDepartment of Medicine, Division of Rheumatology, University of California, San Francisco, San Francisco, CA, USA.
Marina SirotaBakar Computational Health Science Institute, University of California, San Francisco, San Francisco, CA, USA.
J Michelle KahlenbergDepartment of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
Hanna KimJuvenile Myositis Pathogenesis and Therapeutics Unit, National Institute of Arthritis Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
Jessica L TurnierDepartment of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
CARRA Registry Investigators and CARRA Translational Medicine for Juvenile Myositis Working Group

Funding

RESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2M
Juvenile Myositis Pathogenesis and Translational MedicineZIAAR041215 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI KIM, HANNA · 2021 to 2025
$3.3M
Institutional Career Development CoreKL2TR001438 · NCATS · MEDICAL COLLEGE OF WISCONSIN · PI WIDLANSKY, MICHAEL E · 2015 to 2024
$2.9M
Linking Disease Mechanisms and Outcomes in Rheumatic DiseasesK24AR076975 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joanne Michelle Kahlenberg · 2020 to 2026
$910k
Harnessing single cell RNA sequencing and integrative bioinformatics to identify precision therapeutics for dermatomyositisK08AR081983 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jessica Neely · 2023 to 2026
$699k
Harnessing cutaneous transcriptional and myeloid cell signatures to understand treatment response in juvenile dermatomyositisK23AR080789 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jessica Leigh Turnier · 2023 to 2026
$693k
Intramural NIH HHS ZIA AR041215NCATS NIH HHS KL2 TR001438NIAMS NIH HHS K08 AR081983NIAMS NIH HHS K23 AR080789NIAMS NIH HHS K24 AR076975NIAMS NIH HHS P30 AR070155
6 · The paper itself

Abstract

objectivesJuvenile dermatomyositis (JDM) is a heterogeneous autoimmune condition needing targeted treatment approaches and improved understanding of molecular mechanisms driving clinical phenotypes. We utilised exploratory proteomics from a longitudinal North American cohort of patients with new-onset JDM to identify biological pathways at disease onset and follow-up, tissue-specific disease activity, and myositis-specific autoantibody (MSA) status.

methodsWe measured 3072 plasma proteins (Olink panel) in 56 patients with JDM within 12 weeks of starting treatment (from the Childhood Arthritis and Rheumatology Research Alliance Registry and 3 additional sites) and 8 paediatric controls. Twenty-four patients with JDM who had 6-month follow-up samples were assessed. We identified differentially expressed proteins (DEPs) between groups by fitting linear mixed effects models and associated DEPs with validated disease activity measures. We assessed for cell/tissue specificity using the Human Protein Atlas and JDM muscle single nuclei and skin single-cell transcriptomic datasets. Differences within MSA subgroups were also analysed.

resultsWe uncovered persistent dysregulation of innate immune activation, cell death, and redox signalling at 6 months despite multidrug immunosuppression. By leveraging tissue and cell-specific proteomes, we identified overrepresentation of circulating endothelial proteins associated with disease activity and verified endothelial cell marker expression in JDM muscle and skin. We discovered pathways associated with MSA subtypes that reflect JDM phenotypes. NXP2+ JDM-associated proteins reflected angiogenesis and extracellular matrix remodelling and were expressed in endothelial cells and fibroblasts. MDA5+ JDM was associated with circulating type III interferon and surfactant proteins.

conclusionsThese proteomic findings will inform future biomarker and treatment development considering the unique tissue- and autoantibody-associated inflammation in JDM.

Indexed as

AutoantibodiesDermatomyositisProteomeAdolescentBiomarkersChildChild, PreschoolFemaleHumansLongitudinal StudiesMaleMuscle, SkeletalProteomicsSkinAutoantibodiesBiomarkersProteome

Identifiers

PMID40915939
PMCPMC12925510

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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.