Deactivation of endothelium and reduction in angiogenesis in psoriatic skin and synovium by low dose infliximab therapy in combination with stable methotrexate therapy: a prospective single-centre study.
Deactivation of endothelium and reduction in angiogenesis in psoriatic skin and synovium by low dose infliximab therapy in combination with stable methotrexate therapy: a prospective single-centre study.
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DOI：
10.1186/ar1182
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发表时间：
2004
影响因子：
4.9
通讯作者：
Tak PP
中科院分区：
文献类型：
--
作者：
Goedkoop AY;Kraan MC;Picavet DI;de Rie MA;Teunissen MB;Bos JD;Tak PP
银屑病和银屑病关节炎是抗肿瘤坏死因子-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治疗对银屑病皮损皮肤和滑膜组织中粘附分子表达和血管生成的影响，我们进行了英夫利昔单抗治疗联合稳定甲氨蝶呤治疗的前瞻性单中心研究。在一项开放标签研究中，11 名同时患有活动性银屑病和银屑病关节炎的患者在基线以及第 2、6、14 和 22 周时接受了英夫利昔单抗 (3 mg/kg) 输注。此外，患者继续接受稳定的甲氨蝶呤治疗，剂量范围为每周 5 至 20 毫克。在基线时和之后每两周进行一次临床评估，包括银屑病面积和严重程度指数 (PASI) 和疾病活动评分 (DAS)。此外，在治疗前和第4周对目标银屑病斑块进行皮肤活检，并在治疗第4周对目标关节进行滑膜组织活检。进行免疫组织化学分析以检测血管数量、粘附分子的表达和血管生长因子的存在。通过数字图像分析评估染色切片。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 降低至 3.6 ± 0.6 (P ≤ 0.02)。我们发现，与 PASI 的变化相比，DAS 响应存在一些波动，后者随着时间的推移呈现出稳定下降的趋势。 4周后，皮肤和滑膜中的细胞浸润均减少。第4周时，真皮和滑膜中的血管数量显着减少。第4周时，皮肤和滑膜中还发现αvβ3整合素（新生血管形成的标志物）的表达显着减少。此外，第4周时，皮肤和滑膜中粘附分子的表达显着减少。我们还观察到血管内皮生长因子的表达有减少的趋势。 皮肤和滑膜。总之，低剂量英夫利昔单抗治疗可减少新血管生成和内皮失活，从而减少细胞浸润并改善银屑病和银屑病关节炎的临床症状。
Psoriasis and psoriatic arthritis are inflammatory diseases that respond well to anti-tumour necrosis factor-α therapy. To evaluate the effects of anti-tumour necrosis factor-α 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 ≤ 0.02). The mean DAS was reduced from 6.0 ± 0.5 to 3.6 ± 0.6 (P ≤ 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 αvβ3 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.
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影响因子：
168.9
作者：
Chaudhari, U;Romano, P;Gottlieb, AB
通讯作者：
Gottlieb, AB
影响因子：
--
作者：
Kraan, MC;van Kuijk, AWR;Tak, PP
通讯作者：
Tak, PP
影响因子：
4.6
作者：
Drouart, M;Saas, P;Toussirot, É
通讯作者：
Toussirot, É
影响因子：
10.3
作者：
Bhushan, M;McLaughlin, B;Griffiths, CEM
通讯作者：
Griffiths, CEM
DOI：
10.1084/jem.180.3.1141
发表时间：
1994-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Detmar M;Brown LF;Claffey KP;Yeo KT;Kocher O;Jackman RW;Berse B;Dvorak HF
通讯作者：
Dvorak HF