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Keywords:

  • FSHD1A;
  • internally nucleated fibres;
  • inflammation;
  • muscle regeneration;
  • neonatal myosin heavy chain

Background and Objectives

The aim of this study was to investigate whether inflammation and regeneration are prominent in mildly affected muscles of patients with facioscapulohumeral muscular dystrophy type 1A (FSHD1A). Inflammation in muscle has been suggested by MRI studies in patients with FSHD1A.

Methods

We analysed immunohistological and histological stains of muscle biopsies from 24 patients with FSHD1A, using 10 patients with Becker muscular dystrophy (BMD) for comparison.

Results

Internalized nuclei were more prevalent in BMD (23.7 ± 10.8%) vs FSHD1A (6.3 ± 6.8%; P < 0.001), indicating more past regenerating fibres in BMD. Recently regenerating fibres, expressing neonatal myosin heavy chain and vimentin, did not differ significantly between patients with FSHD1A (1.1 ± 2.9%) and patients with BMD (1.8 ± 1.9%). Regeneration was not correlated with the number of KpnI restriction fragment repeats, an FSHD1A-defining genotype property within the D4Z4 locus, or overall disease severity in patients with FSHD1A. Macrophages were more prevalent in FSHD1A (0.50 ± 0.63 per mm2) vs BMD (0.07 ± 0.07 per mm2), whereas inflammatory T cells were equally infrequent.

Conclusions

Macrophages were more prevalent in patients with FSHD1A and could be an important pathogenic mechanism for the initiation of the dystrophic process. Furthermore, regeneration was unrelated to genotype and disease severity in FSHD1A.