Akhmetshina Alfiya, Beer Jürgen, Zwerina Karin, Englbrecht Matthias, Palumbo Katrin, Dees Clara, Reich Nicole, Zwerina Jochen, Szucs Gabriella, Gusinde Johannes, Nevskaya Tatiana, Distler Oliver, Kerjaschki Dontscho, Schett Georg, Distler Jörg H W
University of Erlangen-Nuremberg, Erlangen, Germany.
Arthritis Rheum. 2010 May;62(5):1513-22. doi: 10.1002/art.27406.
Systemic sclerosis (SSc) is a connective tissue disease that is characterized by microvascular disease and tissue fibrosis. Progressive loss and irregular architecture of the small blood vessels are well characterized, but the potential involvement of the lymphatic vessel system has not been analyzed directly in SSc. This study was undertaken to assess whether the lymphatic vascular system is affected in SSc, and whether changes to the lymphatic vessels are associated with dystrophic changes and tissue damage in patients with SSc.
Lymphatic endothelial cells in skin biopsy samples from patients with SSc and age- and sex-matched healthy volunteers were identified by staining for podoplanin and prox-1, both of which are specifically expressed in lymphatic endothelial cells but not in blood vascular endothelial cells. CD31 was used as a pan-endothelial cell marker. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney U, and Spearman's rank correlation tests.
The numbers of podoplanin- and prox-1-positive lymphatic vessels were significantly reduced in patients with SSc as compared with healthy individuals. The number of podoplanin-positive lymphatic precollector vessels was significantly lower in SSc patients with fingertip ulcers than in SSc patients without ulcers. Moreover, the number of lymphatic vessels correlated inversely with the number of fingertip ulcers at the time of biopsy and with the number of fingertip ulcers per year. The inverse correlation between lymphatic precollector vessel counts and fingertip ulcers remained significant after statistical adjustment for the blood vessel count, age, and modified Rodnan skin thickness score.
These results demonstrate a severe reduction in the number of lymphatic capillaries and lymphatic precollector vessels in patients with SSc. Patients with decreased lymphatic vessel counts may be at particularly high risk of developing fingertip ulcers.
系统性硬化症（SSc）是一种以微血管疾病和组织纤维化为特征的结缔组织病。小血管的渐进性丧失和不规则结构已得到充分描述，但淋巴管系统在SSc中是否受累尚未得到直接分析。本研究旨在评估SSc患者的淋巴管系统是否受到影响，以及淋巴管的变化是否与SSc患者的营养不良性改变和组织损伤相关。
通过对足板蛋白（podoplanin）和prox-1进行染色，识别SSc患者及年龄和性别匹配的健康志愿者皮肤活检样本中的淋巴管内皮细胞，这两种蛋白均特异性表达于淋巴管内皮细胞而非血管内皮细胞。CD31用作全内皮细胞标志物。采用Kruskal-Wallis检验、Mann-Whitney U检验和Spearman等级相关检验进行统计分析。
与健康个体相比，SSc患者中足板蛋白和prox-1阳性淋巴管数量显著减少。有指尖溃疡的SSc患者中，足板蛋白阳性的淋巴管前收集血管数量显著低于无溃疡的SSc患者。此外，活检时淋巴管数量与指尖溃疡数量以及每年的指尖溃疡数量呈负相关。在对血管数量、年龄和改良Rodnan皮肤厚度评分进行统计调整后，淋巴管前收集血管数量与指尖溃疡之间的负相关仍然显著。
这些结果表明，SSc患者的淋巴毛细血管和淋巴管前收集血管数量严重减少。淋巴管数量减少的患者发生指尖溃疡的风险可能特别高。
