Goedkoop Amber Y, Kraan Maarten C, Picavet Daisy I, de Rie Menno A, Teunissen Marcel B M, Bos Jan D, Tak Paul P
Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
Arthritis Res Ther. 2004;6(4):R326-34. doi: 10.1186/ar1182. Epub 2004 May 26.
Psoriasis and psoriatic arthritis are inflammatory diseases that respond well to anti-tumour necrosis factor-alpha therapy. To evaluate the effects of anti-tumour necrosis factor-alpha treatment on expression of adhesion molecules and angiogenesis in psoriatic lesional skin and synovial tissue, we performed a prospective single-centre study with infliximab therapy combined with stable methotrexate therapy. Eleven patients with both active psoriasis and psoriatic arthritis received infusions of infliximab (3 mg/kg) at baseline, and at weeks 2, 6, 14 and 22 in an open-label study. In addition, patients continued to receive stable methotrexate therapy in dosages ranging from 5 to 20 mg/week. Clinical assessments, including Psoriasis Area and Severity Index (PASI) and Disease Activity Score (DAS), were performed at baseline and every 2 weeks afterward. In addition, skin biopsies from a target psoriatic plaque and synovial tissue biopsies from a target joint were taken before treatment and at week 4. Immunohistochemical analysis was performed to detect the number of blood vessels, the expression of adhesion molecules and the presence of vascular growth factors. Stained sections were evaluated by digital image analysis. At week 16, the mean PASI was reduced from 12.3 +/- 2.4 at baseline to 1.8 +/- 0.4 (P <or= 0.02). The mean DAS was reduced from 6.0 +/- 0.5 to 3.6 +/- 0.6 (P <or= 0.02). We found some fluctuations in DAS response as compared with the change in PASI, with the latter exhibiting a steady decrease over time. After 4 weeks the cell infiltrate was reduced in both skin and synovium. There was a significant reduction in the number of blood vessels in dermis and synovium at week 4. A significant reduction in the expression of alphavbeta3 integrin, a marker of neovascularization, was also found in both skin and synovium at week 4. In addition, a significant reduction in the expression of adhesion molecules was observed in both skin and synovium at week 4. We also observed a trend toward reduced expression of vascular endothelial growth factor in both skin and synovium. In conclusion, low-dose infliximab treatment leads to decreased neoangiogenesis and deactivation of the endothelium, resulting in decreased cell infiltration and clinical improvement in psoriasis and psoriatic arthritis.
银屑病和银屑病关节炎是对抗肿瘤坏死因子-α治疗反应良好的炎症性疾病。为了评估抗肿瘤坏死因子-α治疗对银屑病皮损和滑膜组织中黏附分子表达及血管生成的影响，我们进行了一项前瞻性单中心研究，采用英夫利昔单抗治疗联合稳定的甲氨蝶呤治疗。11例同时患有活动性银屑病和银屑病关节炎的患者在开放标签研究的基线、第2周、第6周、第14周和第22周接受英夫利昔单抗（3mg/kg）输注。此外，患者继续接受剂量为每周5至20mg的稳定甲氨蝶呤治疗。在基线及之后每2周进行临床评估，包括银屑病面积和严重程度指数（PASI）及疾病活动评分（DAS）。另外，在治疗前及第4周从目标银屑病斑块处取皮肤活检样本，从目标关节处取滑膜组织活检样本。进行免疫组织化学分析以检测血管数量、黏附分子表达及血管生长因子的存在情况。通过数字图像分析对染色切片进行评估。在第16周时，平均PASI从基线时的12.3±2.4降至1.8±0.4（P≤0.02）。平均DAS从6.0±0.5降至3.6±0.6（P≤0.02）。与PASI的变化相比，我们发现DAS反应存在一些波动，后者随时间呈稳定下降。4周后，皮肤和滑膜中的细胞浸润均减少。在第4周时，真皮和滑膜中的血管数量显著减少。在第4周时，皮肤和滑膜中也发现作为新生血管化标志物的αvβ3整合素表达显著降低。此外，在第4周时，皮肤和滑膜中黏附分子的表达均显著降低。我们还观察到皮肤和滑膜中血管内皮生长因子表达有降低的趋势。总之，低剂量英夫利昔单抗治疗导致新生血管生成减少和内皮失活，从而使银屑病和银屑病关节炎中的细胞浸润减少并临床症状改善。
