Mayerl Christina, Del Frari Barbara, Parson Walther, Boeck Guenther, Piza-Katzer Hildegunde, Wick Georg, Wolfram Dolores
a Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, Biocenter , Medical University of Innsbruck , Innsbruck , Austria .
b Department of Internal Medicine III - Cardiology and Angiology , Medical University of Innsbruck , Innsbruck , Austria .
J Plast Surg Hand Surg. 2016 Jun;50(3):171-9. doi: 10.3109/2000656X.2016.1140054. Epub 2016 Feb 6.
Dupuytren's disease is characterised by fibrotic nodule and cord formation in the palmar aponeurosis. The pathophysiology of the disease is still unknown, although cell stress and subsequent activation of immune mechanisms seems to be crucial.
Surgically obtained tissue and blood samples of 100 Dupuytren patients were processed by immunohistochemistry, flow cytometry, as well as immunoscope analysis. Macroscopically normal aponeurotic tissue served as control.
Locally, microvascular alterations and massive infiltration by mononuclear cells (CD3+, CD4 > CD8, CD45RO > CD45RA, S100 protein, CD56, CD68, scarce CD19 and mast cells) forming perivascular clusters were found in DD tissue. Cytokine profiling of fibromatosis tissue-derived T-cells showed a Th1/TH17-weighted immune response. Immunoscope analysis revealed a restricted T-cell receptor α/β repertoire pointing to an (auto)antigen-driven process.
The striking accumulation of immune cells, expression of leukocyte adhesion molecules, as well as pro-inflammatory and pro-fibrotic cytokines near markedly narrowed vessels supports the theory that the abnormal proliferation of fibroblasts and production of extracellular matrix proteins in DD seems to be related to immune-mediated microvascular damage. The restricted T-cell receptor repertoire of intra-lesional T-cells points to an antigen-driven process. T-cells seem to play an important role in the development of Dupuytren's disease.
杜普伊特伦挛缩病的特征是掌腱膜中出现纤维化结节和条索形成。尽管细胞应激及随后免疫机制的激活似乎至关重要,但该疾病的病理生理学仍不清楚。
对100例杜普伊特伦挛缩病患者手术获取的组织和血液样本进行免疫组织化学、流式细胞术以及免疫谱分析。宏观上正常的腱膜组织作为对照。
在杜普伊特伦挛缩病组织中,局部发现微血管改变以及单核细胞(CD3⁺、CD4>CD8、CD45RO>CD45RA、S100蛋白、CD56、CD68、少量CD19和肥大细胞)大量浸润形成血管周围簇。纤维瘤病组织来源的T细胞的细胞因子谱显示出以Th1/TH17为主的免疫反应。免疫谱分析显示T细胞受体α/β库受限,提示存在(自身)抗原驱动过程。
在明显狭窄的血管附近免疫细胞的显著聚集、白细胞黏附分子的表达以及促炎和促纤维化细胞因子的表达支持了这样一种理论,即杜普伊特伦挛缩病中成纤维细胞的异常增殖和细胞外基质蛋白的产生似乎与免疫介导的微血管损伤有关。病变内T细胞受限的T细胞受体库提示存在抗原驱动过程。T细胞似乎在杜普伊特伦挛缩病的发展中起重要作用。