系统性硬化症相关肌病的组织病理学发现：纤维化和微血管病变，无细胞炎症。
Histopathological findings in systemic sclerosis-related myopathy: fibrosis and microangiopathy with lack of cellular inflammation.
作者信息
Corallo Claudio, Cutolo Maurizio, Volpi Nila, Franci Daniela, Aglianò Margherita, Montella Antonio, Chirico Chiara, Gonnelli Stefano, Nuti Ranuccio, Giordano Nicola
机构信息
Scleroderma Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy.
Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy.
出版信息
Ther Adv Musculoskelet Dis. 2017 Jan;9(1):3-10. doi: 10.1177/1759720X16671928. Epub 2016 Oct 3.
OBJECTIVES
The objective of this study was to identify specific histopathological features of skeletal muscle involvement in systemic sclerosis (SSc) patients.
METHODS
A total of 35 out of 112 SSc-patients (32%, including 81% female and 68% diffuse scleroderma) presenting clinical, biological and electromyographic (EMG) features of muscle weakness, were included. Patients underwent vastus lateralis biopsy, assessed for individual pathologic features including fibrosis [type I collagen (Coll-I), transforming growth factor β (TGF-β)], microangiopathy [cluster of differentiation 31 (CD31), pro-angiogenic vascular endothelial growth factor A (VEGF-A), anti-angiogenic VEGF-A165b], immune/ inflammatory response [CD4, CD8, CD20, human leucocyte antigens ABC (HLA-ABC)], and membranolytic attack complex (MAC). SSc biopsies were compared with biopsies of ( = 35) idiopathic inflammatory myopathies (IIMs) and to ( = 35) noninflammatory myopathies (NIMs). Ultrastructural abnormalities of SSc myopathy were also analyzed by transmission electron microscopy (TEM).
RESULTS
Fibrosis in SSc myopathy (81%) is higher compared with IIM (32%, < 0.05) and with NIM (18%, < 0.05). Vascular involvement is dominant in SSc muscle (92%), and in IIM (78%) compared with NIM (21%, < 0.05). In particular, CD31 shows loss of endomysial vessels in SSc myopathy compared with IIM ( < 0.05) and with NIM ( < 0.01). VEGF-A is downregulated in SSc myopathy compared with IIM ( < 0.05) and NIM ( < 0.05). Conversely, VEGF-A165b is upregulated in SSc myopathy. The SSc immune/inflammatory response suggested humoral process with majority (85%) HLA-ABC fibral neoexpression and complement deposits on endomysial capillaries MAC, compared with IIM ( < 0.05), characterized by CD4/CD8/B-cell infiltrate, and NIM ( < 0.05). TEM analysis showed SSc vascular alterations consisting of thickening and lamination of basement membrane and endothelial cell 'swelling' coupled to endomysial/perimysial fibrosis.
CONCLUSIONS
Fibrosis, microangiopathy and humoral immunity are predominant in SSc myopathy, even if it is difficult to identify specific histopathological hallmarks of muscle involvement in SSc, since they could be present also in other (IIM/NIM) myopathies.
目的
本研究的目的是确定系统性硬化症（SSc）患者骨骼肌受累的特定组织病理学特征。
方法
112例出现肌无力临床、生物学和肌电图（EMG）特征的SSc患者中，共有35例（32%，包括81%的女性和68%的弥漫性硬皮病）被纳入研究。患者接受了股外侧肌活检，评估了包括纤维化[Ⅰ型胶原（Coll-I）、转化生长因子β（TGF-β）]、微血管病变[分化簇31（CD31）、促血管生成的血管内皮生长因子A（VEGF-A）、抗血管生成的VEGF-A165b]、免疫/炎症反应[CD4、CD8、CD20、人类白细胞抗原ABC（HLA-ABC）]以及膜攻击复合物（MAC）等个体病理特征。将SSc活检组织与35例特发性炎性肌病（IIM）和35例非炎性肌病（NIM）的活检组织进行比较。还通过透射电子显微镜（TEM）分析了SSc肌病的超微结构异常。
结果
与IIM（32%，P<0.05）和NIM（18%，P<0.05）相比，SSc肌病中的纤维化（81%）程度更高。与NIM（21%，P<0.05）相比，血管受累在SSc肌肉（92%）和IIM（78%）中占主导。特别是，与IIM（P<0.05）和NIM（P<0.01）相比，CD31显示SSc肌病中肌内膜血管缺失。与IIM（P<0.05）和NIM（P<0.05）相比，SSc肌病中VEGF-A表达下调。相反，SSc肌病中VEGF-A165b表达上调。SSc的免疫/炎症反应提示存在体液过程，与以CD4/CD8/B细胞浸润为特征的IIM（P<0.05）和NIM（P<0.05）相比，大多数（85%）的HLA-ABC纤维新生表达以及补体沉积在肌内膜毛细血管MAC上。TEM分析显示SSc血管改变包括基底膜增厚和分层以及内皮细胞“肿胀”，伴有肌内膜/肌束膜纤维化。
结论
纤维化、微血管病变和体液免疫在SSc肌病中占主导，尽管难以确定SSc肌肉受累的特定组织病理学特征，因为它们也可能存在于其他（IIM/NIM）肌病中。
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