Rosu Anca, Ciurea P, Simionescu C, Margaritescu C, Musetescu A E, Ciurea R, Vreju A F
Department of Rheumatology, University of Medicine and Pharmacy, Craiova.
J Med Life. 2008 Jul-Sep;1(3):287-94.
The objective of the study was to analyze several immunohistochemical, histological, and morphometrical aspects of angiogenesis in early rheumatoid arthritis synovium. We aimed to identify possible correlations between the histological and immunohistochemical patterns and the serum levels of VEGF, as well as with clinical and biological markers of disease activity.
35 patients with early rheumatoid arthritis below 12 months from the onset, naive for DMARDs, underwent clinical standard examination as well as serum determinations for CRP, RF. anti-CCP2 antibodies and VEGF. DAS28 value has been determined for each patient in order to assess the disease activity. We performed biopsy sampling through arthroscopy, the synovium fragments beeing histopathologically processed, in order to elaborate a total histological score. Immunohistochemical analysis has been performed with quantification of synovial VEGF, VEGF-R1 and CD34 expression. Standard and activated microvascular density (sMVD and aMVD) have been evaluated through double immunostaining (CD34/ VEGF-R1).
VEGF and VEGF-R1 have been identified with high prevalence in endothelial cells, in lining and sublining synovial cells, as well as in inflammatory cells. The study focuses on the analysis of aMVD, a valuable parameter, representative for active angiogenesis, which proved to correlate significantly with the serum levels of VEGF, the composite histological score as well as with VEGF-R1 and DAS28.
The statistic analysis of the data support VEGF-R1 and aMVD as markers with predictive value regarding activity and progression in early stages of rheumatoid arthritis. The validation of preliminary conclusions oblige to continuous research through extending the study group and inclusion of several others biomarkers involved in synovial angiogenesis.
本研究的目的是分析早期类风湿性关节炎滑膜血管生成的几个免疫组织化学、组织学和形态学方面。我们旨在确定组织学和免疫组织化学模式与血管内皮生长因子（VEGF）血清水平之间，以及与疾病活动的临床和生物学标志物之间可能存在的相关性。
35例发病12个月以内、未使用过改善病情抗风湿药（DMARDs）的早期类风湿性关节炎患者接受了临床标准检查以及血清CRP、类风湿因子（RF）、抗环瓜氨酸肽2（anti-CCP2）抗体和VEGF检测。为评估疾病活动度，测定了每位患者的疾病活动评分28（DAS28）值。我们通过关节镜进行活检取样，对滑膜碎片进行组织病理学处理，以得出总的组织学评分。进行了免疫组织化学分析，对滑膜VEGF、VEGF-R1和CD34表达进行定量。通过双重免疫染色（CD34/VEGF-R1）评估标准微血管密度（sMVD）和活化微血管密度（aMVD）。
在内皮细胞、滑膜衬里层和衬里下层细胞以及炎性细胞中，高比例地检测到VEGF和VEGF-R1。该研究着重分析aMVD，这是一个有价值的参数，代表活跃的血管生成，结果证明其与VEGF血清水平、综合组织学评分以及VEGF-R1和DAS28显著相关。
数据的统计分析支持VEGF-R1和aMVD作为类风湿性关节炎早期活动度和病情进展的预测性标志物。为验证初步结论，必须通过扩大研究组并纳入其他一些参与滑膜血管生成的生物标志物来持续开展研究。
