结节病性肌病中肉芽肿性肌炎的肌病理学与免疫特征

Myopathology and Immune Profile of Granulomatous Myositis in Sarcoid Myopathy.

作者信息

Ruffer Nikolas, Pinal-Fernandez Iago, Kleefeld Felix, Holzer Marie-Therese, Goebel Hans-Hilmar, Schänzer Anne, Casal-Dominguez Maria, Kötter Ina, Görl Norman, Masuhr Florian, Alten Rieke, Braasch Eckart, Grüger Albert, Müller Jörg, Lempert Thomas, Krause Andreas, Huber Tobias B, Liewluck Teerin, Mammen Andrew L, Stenzel Werner, Preusse Corinna, Schneider Udo, Krusche Martin

机构信息

Division of Rheumatology and Systemic Inflammatory Diseases, III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

出版信息

Neuropathol Appl Neurobiol. 2025 Oct;51(5):e70040. doi: 10.1111/nan.70040.

DOI:10.1111/nan.70040

PMID:40928208

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12421948/

Abstract

AIMS

Sarcoid myopathy (SaM) is characterised by granulomatous myositis (GM) and can overlap with inclusion body myositis (IBM), a late-onset chronic idiopathic inflammatory myopathy with a still enigmatic pathogenesis. As GM can occur in different clinical contexts, we aimed to examine the histomorphologic features and gene expression profiles in cases of definite SaM that may inform diagnostic and therapeutic considerations.

METHODS

We performed a multidimensional characterisation of muscle biopsy specimens from patients with 'pure SaM' (n=17), SaM with concomitant IBM (SaM-IBM) (n=2), including histopathologic and ultrastructural analysis in addition to quantitative real-time polymerase chain reaction. Additionally, bulk RNA sequencing was performed on 38 muscle biopsy specimens from patients with SaM (including SaM-IBM) (n=30) and NGI (n=8).

RESULTS

Histopathological analysis revealed a pattern of endomysial and perimysial granulomatous inflammation frequently extending to the fascia, endomysial fibrosis, muscle fibre atrophy, variation in muscle fibre size and capillary thickening. Findings from immunohistochemical studies established Chitinase 1 as a pure giant cell marker in SaM. On a subcellular level, 'pure SaM' was characterised by focal accumulation of large swollen mitochondria with rare cristae but an absence of irregular cristae. Transcriptomic analysis of patients with SaM confirmed markedly elevated expression of both type 1 and type 2 human leukocyte antigen molecules. Macrophage activity markers were highly elevated. Consistent with histologic findings, CHIT1 was specifically overexpressed in SaM samples but not in 'pure IBM' muscle biopsy specimens.

CONCLUSIONS

SaM is characterised by a stereotypical appearance at the histopathologic level and disease-specific immune dysregulation that involves macrophage function and maturation. SaM-IBM represents a noteworthy overlap syndrome that shares multiple dysregulated immune pathways with 'pure SaM'.

摘要

目的

结节病性肌病（SaM）以肉芽肿性肌炎（GM）为特征，且可与包涵体肌炎（IBM）重叠，后者是一种发病较晚的慢性特发性炎性肌病，其发病机制仍不明。由于GM可出现在不同临床背景中，我们旨在研究确诊的SaM病例的组织形态学特征和基因表达谱，为诊断和治疗提供参考。

方法

我们对“单纯SaM”患者（n = 17）、合并IBM的SaM（SaM-IBM）患者（n = 2）的肌肉活检标本进行了多维度特征分析，包括组织病理学和超微结构分析，以及定量实时聚合酶链反应。此外，对30例SaM（包括SaM-IBM）患者和8例非肉芽肿性肌炎（NGI）患者的38份肌肉活检标本进行了全转录组RNA测序。

结果

组织病理学分析显示，肌内膜和肌束膜肉芽肿性炎症常延伸至筋膜，伴有肌内膜纤维化、肌纤维萎缩、肌纤维大小不一和毛细血管增厚。免疫组织化学研究结果确定几丁质酶1为SaM中的一种纯巨细胞标志物。在亚细胞水平上，“单纯SaM”的特征是大的肿胀线粒体局灶性聚集，嵴少见，但无不规则嵴。对SaM患者的转录组分析证实，1类和2类人类白细胞抗原分子的表达均显著升高。巨噬细胞活性标志物高度升高。与组织学结果一致，CHIT1在SaM样本中特异性过表达，但在“单纯IBM”肌肉活检标本中未过表达。