Journal of neuromuscular diseases · 2025
Immunohistological and electron microscopy profile of unique TIRM-MRI guided muscle biopsies of FSHD patients.
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Greco Anna, Kusters Benno, Mann Ritse, Futterer Jurgen, de Jong Leon, Welling Yordy, Ploegmakers Marieke, Pruijn Ger Jm, Joosten Leo Ab, van Engelen Baziel G M
Аннотация
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.
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.