Early effects of tumour necrosis factor α blockade on skin and synovial tissue in patients with active psoriasis and psoriatic arthritis
Early effects of tumour necrosis factor α blockade on skin and synovial tissue in patients with active psoriasis and psoriatic arthritis
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DOI：
10.1136/ard.2003.018085
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发表时间：
2004-07-01
影响因子：
27.4
通讯作者：
Tak, PP
中科院分区：
文献类型：
--
作者：
Goedkoop, AY;Kraan, MC;Tak, PP
背景：使用英夫利昔单抗（一种嵌合抗 TNFα 抗体）阻断肿瘤坏死因子 α (TNFα) 是治疗银屑病和银屑病关节炎 (PsA) 的有效方法。目的：分析英夫利昔单抗治疗对连续皮肤和滑膜组织活检样本的早期影响。方法：12 名同时患有活动性银屑病和 PsA 的患者接受单次输注英夫利昔单抗 (3 mg/kg) (n = 6) 或安慰剂 (n = 6) 静脉注射。在基线和治疗后 48 小时获取滑膜组织和病变皮肤活检标本。进行免疫组织化学分析以分析炎症浸润。通过 TUNEL 测定和抗 caspase-3 抗体的免疫组织化学染色进行凋亡细胞的原位检测。通过数字图像分析评估染色的组织切片。 结果：英夫利昔单抗治疗后，病变表皮（基线 37 (11) 个细胞/mm，48 小时 26 (11)，p = 0.028）和滑膜组织（67 (56) 个细胞/mm(2) v 32 (30)，p = 0.043）的平均 (SEM) T 细胞数量显着减少，但没有显着减少。安慰剂治疗后（表皮 18 (8) v 43 (20)，NS；滑膜 110 (62) v 46 (21)，NS）。同样，抗 TNFα 治疗后滑膜下衬中的巨噬细胞数量显着减少（100 (73) v 10 (8)，p = 0.043）。细胞数量的变化不能用炎症部位细胞凋亡的诱导来解释。 结论：抗 TNFα 治疗在银屑病和银屑病关节炎中的作用可能是通过治疗开始后早期病变皮肤和发炎滑膜组织中细胞浸润的减少来解释的。
Background: Tumour necrosis factor alpha (TNFalpha) blockade using infliximab, a chimeric anti-TNFalpha antibody, is an effective treatment for both psoriasis and psoriatic arthritis (PsA).Objective: To analyse the early effects of infliximab treatment on serial skin and synovial tissue biopsy samples.Methods: Twelve patients with both active psoriasis and PsA received a single infusion of either infliximab (3 mg/kg) (n = 6) or placebo (n = 6) intravenously. Synovial tissue and lesional skin biopsy specimens were obtained at baseline and 48 hours after treatment. Immunohistochemical analysis was performed to analyse the inflammatory infiltrate. In situ detection of apoptotic cells was performed by TUNEL assay and by immunohistochemical staining with anti-caspase-3 antibodies. Stained tissue sections were evaluated by digital image analysis.Results: A significant reduction in mean (SEM) T cell numbers was found in both lesional epidermis (baseline 37 (11) cells/mm, 48 hours 26 (11), p = 0.028) and synovial tissue (67 (56) cells/mm(2) v 32 (30), p = 0.043) after infliximab treatment, but not after placebo treatment (epidermis 18 (8) v 43 (20), NS; synovium 110 (62) v 46 (21), NS). Similarly, the number of macrophages in the synovial sublining was significantly reduced after anti-TNFalpha treatment (100 (73) v 10 (8), p = 0.043). The changes in cell numbers could not be explained by induction of apoptosis at the site of inflammation.Conclusions: The effects of anti-TNFalpha therapy in psoriasis and psoriatic arthritis may be explained by decreased cell infiltration in lesional skin and inflamed synovial tissue early after initiation of treatment.