Muscle fibrosis as a prognostic biomarker in facioscapulohumeral muscular dystrophy: a retrospective cohort study

Acta Neuropathologica Communications

Research

Elvira Ragozzino¹  Ornella Parolini²  Lorena Di Pietro²  Andrea Papait²  Mauro Monforte³  Sara Bortolani³  Enzo Ricci⁴  Giorgio Tasca⁵ 

[1] Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy;Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy;Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;Unità Operativa Complessa di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;Unità Operativa Complessa di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;Istituto di Neurologia, Università Cattolica del Sacro Cuore, Rome, Italy;Unità Operativa Complessa di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trusts, Newcastle Upon Tyne, UK;

关键词: Muscle fibrosis;    Skeletal muscle;    Facioscapulohumeral muscular dystrophy;    Neuromuscular disease;    Biomarker;    Muscle magnetic resonance imaging;    Immune cell infiltrates;    Muscle degeneration;   

DOI  :  10.1186/s40478-023-01660-4

 received in 2023-07-25, accepted in 2023-09-25,  发布年份 2023

来源: Springer

【 摘 要 】

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant epigenetic disorder with highly variable muscle involvement and disease progression. Ongoing clinical trials, aimed at counteracting muscle degeneration and disease progression in FSHD patients, increase the need for reliable biomarkers. Muscle magnetic resonance imaging (MRI) studies showed that the appearance of STIR-positive (STIR+) lesions in FSHD muscles represents an initial stage of muscle damage, preceding irreversible adipose changes. Our study aimed to investigate fibrosis, a parameter of muscle degeneration undetectable by MRI, in relation to disease activity and progression of FSHD muscles. We histologically evaluated collagen in FSHD1 patients’ (STIR+ n = 27, STIR− n = 28) and healthy volunteers’ (n = 12) muscles by picrosirius red staining. All patients (n = 55) performed muscle MRI before biopsy, 45 patients also after 1 year and 36 patients also after 2 years. Fat content (T1 signal) and oedema/inflammation (STIR signal) were evaluated at baseline and at 1- and 2-year MRI follow-up. STIR+ muscles showed significantly higher collagen compared to both STIR− (p = 0.001) and healthy muscles (p < 0.0001). STIR− muscles showed a higher collagen content compared to healthy muscles (p = 0.0194). FSHD muscles with a worsening in fatty infiltration during 1- (P = 0.007) and 2-year (P < 0.0001) MRI follow-up showed a collagen content of 3.6- and 3.7-fold higher compared to FSHD muscles with no sign of progression. Moreover, the fibrosis was significantly higher in STIR+ muscles who showed a worsening in fatty infiltration in a timeframe of 2 years compared to both STIR− (P = 0.0006) and STIR+ muscles with no sign of progression (P = 0.02). Fibrosis is a sign of muscle degeneration undetectable at MRI never deeply investigated in FSHD patients. Our data show that 23/27 of STIR+ and 12/28 STIR− muscles have a higher amount of collagen deposition compared to healthy muscles. Fibrosis is higher in FSHD muscles with a worsening in fatty infiltration thus suggesting that its evaluation with innovative non-invasive techniques could be a candidate prognostic biomarker for FSHD, to be used to stratify patients and to evaluate the efficacy of therapeutic treatments.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 5

Fig. 3

Fig. 1

Fig. 2

Fig. 1

Fig. 2

Fig. 1