van Kuijk A W R, Reinders-Blankert P, Smeets T J M, Dijkmans B A C, Tak P P
Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, F4-218, PO Box 22700, 1100 DE Amsterdam, The Netherlands.
Ann Rheum Dis. 2006 Dec;65(12):1551-7. doi: 10.1136/ard.2005.050963. Epub 2006 May 25.
The synovial tissue is a primary target of many inflammatory arthropathies, including psoriatic arthritis (PsA). Identification of proinflammatory molecules in the synovium may help to identify potentially therapeutic targets.
To investigate extensively the features of cell infiltration and expression of mediators of inflammation and joint destruction in the synovium of patients with PsA compared with patients with rheumatoid arthritis matched for disease duration and use of drugs.
Multiple synovial tissue biopsy specimens were obtained by arthroscopy from an inflamed joint in 19 patients with PsA (eight oligoarthritis, 11 polyarthritis) and 24 patients with rheumatoid arthritis. Biopsy specimens were analysed by immunohistochemistry to detect T cells, plasma cells, fibroblast-like synoviocytes, macrophages, proinflammatory cytokines, matrix metalloproteinases and tissue inhibitor metalloproteinase-1, adhesion molecules and vascular markers. Stained sections were evaluated by digital image analysis.
The synovial infiltrate of patients with PsA and rheumatoid arthritis was comparable with regard to numbers of fibroblast-like synoviocytes and macrophages. T cell numbers were considerably lower in the synovium of patients with PsA. The number of plasma cells also tended to be lower in PsA. The expression of tumour necrosis factor alpha (TNFalpha), interleukin (IL) 1beta, IL6 and IL18 was as high in PsA as in rheumatoid arthritis. The expression of matrix metalloproteinases, adhesion molecules and vascular markers was comparable for PsA and rheumatoid arthritis.
These data show increased proinflammatory cytokine expression in PsA synovium, comparable to results obtained for rheumatoid arthritis, and support the notion that, in addition to TNFalpha blockade, there may be a rationale for treatments directed at IL1beta, IL6 and IL18.
滑膜组织是包括银屑病关节炎(PsA)在内的许多炎症性关节病的主要靶点。识别滑膜中的促炎分子可能有助于确定潜在的治疗靶点。
广泛研究与疾病病程和药物使用相匹配的类风湿关节炎患者相比,PsA患者滑膜中的细胞浸润特征以及炎症和关节破坏介质的表达情况。
通过关节镜从19例PsA患者(8例寡关节炎,11例多关节炎)和24例类风湿关节炎患者的发炎关节获取多个滑膜组织活检标本。通过免疫组织化学分析活检标本,以检测T细胞、浆细胞、成纤维样滑膜细胞、巨噬细胞、促炎细胞因子、基质金属蛋白酶和金属蛋白酶组织抑制剂-1、黏附分子和血管标志物。通过数字图像分析评估染色切片。
PsA患者和类风湿关节炎患者的滑膜浸润在成纤维样滑膜细胞和巨噬细胞数量方面具有可比性。PsA患者滑膜中的T细胞数量显著较低。PsA患者的浆细胞数量也往往较低。肿瘤坏死因子α(TNFα)、白细胞介素(IL)1β、IL6和IL18在PsA中的表达与类风湿关节炎中的表达一样高。PsA和类风湿关节炎中基质金属蛋白酶、黏附分子和血管标志物的表达具有可比性。
这些数据表明,PsA滑膜中促炎细胞因子表达增加,与类风湿关节炎的结果相当,并支持这样一种观点,即除了TNFα阻断外,针对IL1β、IL6和IL18的治疗可能也有理论依据。