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

IF 3.4 4区医学 Q2 CLINICAL NEUROLOGY

Journal of neuromuscular diseases Pub Date : 2025-10-06 DOI:10.1177/22143602251380426

Anna Greco, Benno Kusters, Ritse Mann, Jurgen Futterer, Leon de Jong, Yordy Welling, Marieke Ploegmakers, Ger Jm Pruijn, Leo Ab Joosten, Baziel G M van Engelen

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引用次数: 0

Abstract

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.

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独特的TIRM-MRI引导下FSHD患者肌肉活检的免疫组织学和电镜特征。

背景：FSHD是一种复杂的表观遗传发病机制的遗传性肌病，无因果治疗。炎症被认为是肌肉病理的原因之一，但其性质尚不清楚。目的：比较mri引导下FSHD肌肉活检与健康对照组（HC）的炎症浸润和形态学变化。方法：我们对43例遗传确诊的FSHD患者（50±12岁，51%男性）进行了涡轮反转恢复强度（TIRM）和DIXON MRI检查，以评估炎症和脂肪浸润。从24例至少有一个TIRM +腿部肌肉的患者中，进行了两次mri引导活检（TIRM +和TIRM-）。8例HC患者（36±12岁，男性62%）进行针活检作为对照。样品进行苏木精-苯氧辛染色，免疫检测CD3、CD4、CD8、CD56、CD68、HLA-ABC、HLA-DR和MAC，电镜下进行超微结构分析。结果：与配对的TIRM-和HC样品相比，TIRM + FSHD样品的组织病理学和炎症等级明显更高。67%的TIRM +和20%的TIRM-肌肉存在炎症浸润，主要是CD8 +淋巴细胞和CD68 +巨噬细胞。电镜显示在TIRM +样品中肌纤维频繁紊乱。结论：我们的研究结果证实了TIRM高强度是活动性疾病的生物标志物，与组织病理学和炎症相关。炎症在FSHD中的发病率似乎被低估了，这突出了其在疾病发病机制中的作用。这些结果支持靶向炎症作为FSHD的潜在治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of neuromuscular diseases Medicine-Neurology (clinical)

CiteScore

5.10

自引率

6.10%

发文量

102

期刊介绍： The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.