Division of Pathology, CHU Sainte-Justine, Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec, Canada.
Division of Rheumatology, Jewish General Hospital, Department of Medicine, McGill University, Montréal, Québec, Canada.
Neuropathol Appl Neurobiol. 2022 Dec;48(7):e12840. doi: 10.1111/nan.12840. Epub 2022 Aug 12.
We aim to perform ultrastructural and histopathological analysis of muscle biopsies from a large group of systemic sclerosis (SSc) patients, including some with early/mild SSc features, and examine whether capillary pathology differentiates 'scleromyositis' (SM) from other auto-immune myositis (AIM) subsets.
Muscle biopsies from a total of 60 SM patients and 43 AIM controls from two independent cohorts were examined by electron microscopy, collagen-4 immunofluorescence (Col4IF) and routine light microscopy.
Ultrastructural examination revealed prominent capillary basement membrane (BM) reduplication (4+ layers in >50% of capillaries) in 65% of SM vs 0% of AIM controls (p < 0.001). In SM cases without prominent BM reduplication, capillary dilation was the most distinctive feature, present in 8% of capillaries in SM vs 2% in controls (p = 0.001). Accumulation of ensheathed pericyte processes was another characteristic feature of SM and closely correlated with the degree of BM reduplication (r = 0.833, p < 0.001). On light microscopy, BM marker Col4IF revealed more frequent capillary enlargement in SM than in controls (84% vs 21%, p < 0.001). SM cases were classified as non-inflammatory myopathy (36%), non-specific myositis (33%) or immune-mediated necrotizing myopathy (31%), but despite this histopathological heterogeneity, prominent BM reduplication remained a constant finding. In the 16 SM patients with early/mild SSc features, 63% showed prominent BM reduplication.
These results show that capillary pathology, and in particular prominent capillary BM reduplication, is the hallmark histopathological feature of SM even in patients with early/mild SSc and support the concept of SM as an organ manifestation of SSc and a distinct subset of AIM.
我们旨在对来自一大组系统性硬化症（SSc）患者的肌肉活检进行超微结构和组织病理学分析，包括一些具有早期/轻度 SSc 特征的患者，并检查毛细血管病理学是否能区分“硬皮病性肌炎（SM）”与其他自身免疫性肌炎（AIM）亚组。
对来自两个独立队列的总共 60 名 SM 患者和 43 名 AIM 对照组的肌肉活检进行电子显微镜、IV 型胶原免疫荧光（Col4IF）和常规光镜检查。
超微结构检查显示，65%的 SM 患者毛细血管基底膜（BM）显著复层（超过 50%的毛细血管有 4 层以上），而对照组为 0%（p<0.001）。在没有明显 BM 复层的 SM 病例中，毛细血管扩张是最具特征性的特征，在 SM 中的毛细血管中占 8%，而在对照组中占 2%（p=0.001）。被鞘包围的周细胞过程的积累是 SM 的另一个特征性特征，与 BM 复层的程度密切相关（r=0.833，p<0.001）。在光镜下，BM 标志物 Col4IF 显示 SM 中比对照组更频繁地出现毛细血管扩大（84%比 21%，p<0.001）。SM 病例分为非炎症性肌病（36%）、非特异性肌炎（33%）或免疫介导的坏死性肌病（31%），但尽管存在这种组织病理学异质性，明显的 BM 复层仍然是一个恒定的发现。在 16 名具有早期/轻度 SSc 特征的 SM 患者中，63%的患者出现明显的 BM 复层。
这些结果表明，毛细血管病理学，特别是明显的毛细血管 BM 复层，是 SM 的标志性组织病理学特征，即使在具有早期/轻度 SSc 的患者中也是如此，并支持 SM 作为 SSc 的器官表现和 AIM 的一个独特亚组的概念。
