Evidence map›Paper›PMID 40568658›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Identification of a distinctive gene signature in granulomatous myositis.

Iago Pinal-Fernandez, Nikolas Ruffer, Maria Casal-Dominguez, Katherine Pak, Felix Kleefeld, Corinna Preusse, Raphael Kirou, Travis B Kinder, Stefania Del Orso, Faiza Naz and 9 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Iago Pinal-FernandezMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Nikolas RufferDivision of Rheumatology and Systemic Inflammatory Diseases, III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Maria Casal-DominguezMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Katherine PakMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Felix KleefeldCharité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Neurology, Charitéplatz 1, 10117 Berlin, Germany.
Corinna PreusseCharité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Neuropathology, Charitéplatz 1, 10117 Berlin, Germany.
Raphael KirouMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Travis B KinderMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Stefania Del OrsoMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Faiza NazMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Shamima IslamMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Gustavo Gutierrez-CruzMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Margherita MiloneDivision of Neuromuscular Medicine, Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Albert Selva-O'CallaghanSystemic Autoimmune Disease Unit, Vall d'Hebron Institute of Research, Barcelona, Spain.
Jose C MilisendaMuscle Research Unit, Internal Medicine Department, Hospital Clinic, Barcelona, Spain.
Udo SchneiderDepartment of Rheumatology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
Teerin LiewluckDivision of Neuromuscular Medicine, Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Werner StenzelCharité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Neuropathology, Charitéplatz 1, 10117 Berlin, Germany.
Andrew L MammenMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objectives: Granulomatous myositis (GM) is defined by focal collections of activated macrophages that fuse to form multinucleated cells that aggregate into granulomas within skeletal muscle. This study aimed to elucidate the pathophysiology of GM by defining its specific transcriptomic profile. Methods: Bulk RNA sequencing was performed on 722 muscle biopsies, including 38 from patients with GM, other myopathies, and healthy comparators. Spatial transcriptomics and immunohistochemistry assays were used to identify the location of specific transcripts and proteins within the tissue. Results: The transcriptomic signature of GM muscle biopsies was characterized by high levels of IFNγ, IFNγ-inducible genes, and proinflammatory cytokine genes including IL1B, TNF, and TGFB1. The expression levels of 1293 specifically upregulated and 256 specifically downregulated genes were highly correlated with transcriptomic markers of disease activity. Support vector machine models using this gene set identified GM with an AUC of 99.6% (99.0%-99.9%) and an accuracy of 98.6% (98.2%-98.9%). Expression of CHIT1, the most significantly upregulated gene, strongly correlated with disease severity and was detected at the RNA and protein level in granulomas and giant cells. Conclusions: GM is transcriptomically characterized by a strong IFNγ signature and overexpression of proinflammatory cytokines, including IL1B, TNF, and TGFB1. Additionally, it exhibits a unique transcriptomic profile, including CHIT1, which correlates with disease activity.

Indexed as

Granulomatous diseasesMuscle BiopsyMyositisPolymyositisRNA-sequencingSarcoid

Identifiers

PMID40568658
PMCPMC12191085

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Registered trials

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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.