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Multicenter Study
. 2025 Jun 26;272(7):480.
doi: 10.1007/s00415-025-13192-z.

Mitochondrial pathology in inflammatory myopathies: a marker of worse clinical outcome

Antonio Lauletta  1 , Luca Bosco  2 , Gioia Merlonghi  3 , Yuri Matteo Falzone  2 , Marta Cheli  4 , Roberta Piera Bencivenga  5 , Dario Zoppi  5 , Marco Ceccanti  6 , Felix Kleefeld  7 , Sarah Léonard-Louis  8 , Werner Stenzel  9 , Olivier Benveniste  10 , Lorenzo Maggi  4 , Stefano Carlo Previtali  2   11 , Matteo Garibaldi  3
Affiliations
Multicenter Study

Mitochondrial pathology in inflammatory myopathies: a marker of worse clinical outcome

Antonio Lauletta et al. J Neurol. .

Abstract

Objectives: Mitochondrial dysfunction is well documented in inclusion body myositis (IBM), but its role in non-IBM myositis remains unclear. This study aimed to investigate the prevalence and clinical significance of mitochondrial pathology in non-IBM myositis and to assess its potential role as a marker for disease progression towards IBM, treatment response, and clinical outcomes.

Methods: Muscle biopsies from 850 patients with inflammatory myopathy (IM) across 6 neuromuscular centers in Italy, France, and Germany were retrospectively analyzed. Inclusion required meeting diagnostic criteria for definite adult IM, mitochondrial pathology (age-exceeding numbers of COX-negative fibers), and exclusion of definite IBM according to Hilton-Jones 2013 criteria. The percentage of COX-negative fibers was quantified, correlated with clinical outcomes, and compared with myositis control cases without relevant signs of mitochondrial alterations.

Results: Twenty-five patients with non-IBM myositis and mitochondrial abnormalities were identified. These patients, predominantly women (68%), had a mean onset age of 58.8 years. Polymyositis with mitochondrial pathology (PM-Mito) and nonspecific myositis (NSM) were the most prevalent subtypes (72%). The mean percentage of COX-negative fibers was 3% (0.25-8.5%) in these patients. The presence of mitochondrial pathology was associated with treatment refractoriness and worse clinical outcome evaluated based on residual muscle weakness and the level of independence (p < 0.005). A higher percentage of COX-negative fibers also correlated with poorer clinical outcomes (p = 0.031). Four patients, initially diagnosed with PM-Mito and NSM, progressed to definite IBM.

Conclusions: Mitochondrial dysfunction represents a key element informing about disease severity and poor clinical outcomes in non-IBM myositis. It may predict progression to IBM, especially in PM-Mito and NSM, and guide treatment strategies.

Keywords: Inclusion body myositis (IBM); Inflammatory myopathies; Mitochondrial dysfunction; Polymyositis with mitochondrial pathology (PM-Mito).

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Conflict of interest statement

Declarations. Conflicts of interest: On behalf of all the authors, Antonio Lauletta states that there is no conflict of interest. Ethical approval: The study obtained the institutional review board/ethical approval and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All patients gave their informed consent to participate in this study.

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