期刊
JOURNAL OF NEUROMUSCULAR DISEASES
卷 9, 期 1, 页码 83-93出版社
IOS PRESS
DOI: 10.3233/JND-210711
关键词
Facioscapulohumeral muscular dystrophy (FSHD); disease biomarkers; Interleukin-6; cytokines
资金
- Centre Hospitalier Universitaire de Nice [13AOI-01]
- French Government (National Research Agency) through the 'Investments for the Future' (LABEX SIGNAL-IFE) [ANR-13-BSV1-0004-04, ANR-11-LABX-0028-01]
- University Hospital Federation (FHU) OncoAge
- National Institute of Arthritis, Musculoskeletal, and Skin Diseases, NIH [R01AR070432]
- Agence Nationale de la Recherche (ANR) [ANR-13-BSV1-0004] Funding Source: Agence Nationale de la Recherche (ANR)
The study identified IL-6 as a potential serum biomarker of FSHD severity in a large cohort of FSHD1 adult patients. Different levels of IL-6 were observed in patients with different disease severity, and IL-6 levels correlated positively with disease severity and DUX4 expression.
Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common myopathies in adults, displaying a progressive, frequently asymmetric involvement of a typical muscles' pattern. FSHD is associated with epigenetic derepression of the polymorphic D4Z4 repeat on chromosome 4q, leading to DUX4 retrogene toxic expression in skeletal muscles. Identifying biomarkers that correlate with disease severity would facilitate clinical management and assess potential FSHD therapeutics' efficacy. Objectives: This study purpose was to analyze serum cytokines to identify potential biomarkers in a large cohort of adult patients with FSHD. Methods: We retrospectively measured the levels of 20 pro-inflammatory and regulatory cytokines in sera from 100 genetically confirmed adult FSHD1 patients. Associations between cytokine concentrations and various clinical scores were investigated. We then measured serum and muscle interleukin 6 (IL-6) levels in a validated FSHD-like mouse model, ranging in severity and DUX4 expression. Results: IL-6 was identified as the only cytokine with a concentration correlating with several clinical severity and functional scores, including Clinical Severity Score, Manual Muscle Testing sum score, Brooke and Vignos scores. Further, FSHD patients displayed overall IL-6 levels more than twice high as control, and patients with milder phenotypes exhibited lower IL-6 serum concentration than those with severe muscular weakness. Lastly, an FSHD-like mouse model analysis confirmed that IL-6 levels positively correlate with disease severity and DUX4 expression. Conclusions: Serum IL-6, therefore, shows promise as a serum biomarker of FSHD severity in a large cohort of FSHD1 adult patients.
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