Alterations in systemic and skeletal muscle myostatin regulation are most prominent at disease onset and associate with muscle-related outcomes in idiopathic inflammatory myopathies
Authors' conclusion
Early IIM is characterized by dissociation between reduced circulating MSTN and activation of MSTN signalling in skeletal muscle, which diminishes with treatment and disease chronicity. Circulating FSTL3 is associated with systemic inflammation, disease activity and patient-reported outcomes, with pronounced associations in female patients.
Study context
- Population
- Patients with idiopathic inflammatory myopathies (IIM) and healthy controls (HC)101 IIM, 134 HC
- Exposure
- Newly diagnosed IIM vs IIM after six months of therapy vs chronic IIM vs HC
- HCn = 134reference
- Outcome
- Systemic and skeletal muscle MSTN regulation
Methodological detailslongitudinal (disease onset, after six months of therapy, chronic IIM), linear mixed-effects models, partial least squares regression, Muscle biopsies: 59 newly diagnosed, 19 after six months of therapy, 19 chronic IIM, 21 HC
- Longitudinal (disease onset, after six months of therapy, chronic IIM)
- Linear mixed-effects models
- Partial least squares regression
- Muscle biopsies: 59 newly diagnosed, 19 after six months of therapy, 19 chronic IIM, 21 HC
Main finding
As reported in the abstract
- Newly diagnosed IIM had significantly lower circulating myostatin (MSTN) and higher follistatin (FST) than chronic patients and HC
- Activin A (ActA) elevated only in chronic disease
- After normalization to body cell mass, MSTN remained reduced in newly diagnosed patients and increased after six months of therapy; FST, ActA and FSTL3 did not change significantly
- FSTL3 strongly associated with systemic inflammation, disease activity and reduced physical and mental health scores, predominantly in female patients
- In muscle, newly diagnosed patients showed increased expression of MSTN pathway genes and proteins (MSTN, SMAD2/3, ubiquitin-proteasome components)
- A latent component linked MSTN pathway activation with muscle disease activity
Observational data: associations, not effects.
Original publication
Alterations in systemic and skeletal muscle myostatin regulation are most prominent at disease onset and associate with muscle-related outcomes in idiopathic inflammatory myopathies. Arthritis Res Ther. Published 2 July 2026. doi:10.
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