Immunohistological and electron microscopy profile of unique TIRM-MRI guided muscle biopsies of FSHD patients.

BACKGROUND

FSHD is an inherited myopathy with complex epigenetic pathogenesis and no causal treatment. Inflammation is thought to contribute to muscle pathology, but its nature remains unclear.

OBJECTIVE

To characterize inflammatory infiltrates and morphological changes in MRI-guided FSHD muscle biopsies compared to healthy controls (HC).

METHODS

We performed turbo inversion recovery magnitude (TIRM) and DIXON MRI on 43 genetically confirmed FSHD patients (50 ± 12 years, 51% men) to assess inflammation and fatty infiltration. From 24 patients with at least one TIRM + leg muscle, two MRI-guided biopsies (TIRM + and TIRM-) were obtained. Needle biopsies from 8 HC (36 ± 12 years, 62% men) served as controls. Samples underwent hematoxylin-phloxine staining and immunodetection of CD3, CD4, CD8, CD56, CD68, HLA-ABC, HLA-DR, and MAC. Electron microscopy provided ultrastructural analysis.

RESULTS

TIRM + FSHD samples showed significantly higher histopathology and inflammation grades than paired TIRM- and HC samples. Inflammatory infiltrates, mainly CD8 + lymphocytes and CD68 + macrophages, were present in 67% of TIRM + and 20% of TIRM- muscles. Electron microscopy revealed frequent myofibrillar disorganization in TIRM + samples.

CONCLUSION

Our findings validate TIRM hyperintensity as a biomarker for active disease, correlating with histopathology and inflammation. The incidence of inflammation in FSHD appears underestimated, highlighting its role in disease pathogenesis. These results support targeting inflammation as a potential therapeutic strategy in FSHD.