Evidence map›Paper›PMID 40502568›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Local immunoglobulin expression in myositis is associated with interferon gamma signaling and correlates with disease activity.

Iago Pinal-Fernandez, Caroline Metz, Maria Casal-Dominguez, Katherine Pak, Raphael Kirou, Stefania Dell'Orso, Faiza Naz, Shamima Islam, Gustavo Gutierrez-Cruz, Werner Stenzel and 3 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.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Iago Pinal-FernandezMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Caroline MetzMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
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.
Raphael KirouMuscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Stefania Dell'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.
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.
Albert Selva-O'CallaghanSystemic Autoimmune Disease Section, Vall d'Hebron Institute of Research, Barcelona, Spain.
Jose C MilisendaMuscle Research Unit, Internal Medicine Service, Hospital Clinic, Barcelona, Spain.
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: Autoantibodies may play a role in the pathogenesis of myositis and are locally produced within muscle tissue. This study aimed to characterize the local expression of immunoglobulin genes across different subgroups of myositis, identify pathways associated with this expression, and evaluate correlations with disease activity. Methods: Bulk RNA sequencing was performed on muscle biopsies from 289 individuals, including patients with various forms of myositis and healthy controls. Expression levels of immunoglobulin gene regions were compared across clinical and autoantibody-defined subgroups. Pathway enrichment analysis and unsupervised clustering were conducted, and correlations between immunoglobulin gene expression and disease activity were assessed. Results: Local immunoglobulin gene expression was highest in inclusion body myositis (IBM) and antisynthetase syndrome (ASyS), followed by dermatomyositis, and lowest in immune-mediated necrotizing myopathy. Among isotypes, IgG, IgA, and IgM predominated, while IgD and IgE expression was minimal. Certain immunoglobulin VJ segments were more frequently used across all patients, with no significant differences in specific region usage between patient groups. Immunoglobulin gene expression strongly correlated with disease activity, particularly in patients with anti-Mi2, anti-MDA5, anti-Jo1 autoantibodies, and IBM. Pathway analysis revealed a robust association between immunoglobulin expression and interferon-gamma (IFN-γ) signaling. Unsupervised clustering based solely on immunoglobulin gene expression clearly separated healthy controls from patients with ASyS and IBM. Conclusions: Immunoglobulin is locally expressed in the muscle of patients with myositis, particularly IBM and ASyS. This expression correlates with disease activity, involves preferential usage of specific isotypes and gene segments, and is closely linked to IFN-γ-associated immune pathways.

Indexed as

antibodyautoantibodiesdermatomyositisimmune-mediated necrotizing myositisRNA-sequencing

Identifiers

PMID40502568
PMCPMC12155027

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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.