Pathway Analysis of Skin from Psoriasis Patients after Adalimumab Treatment Reveals New Early Events in the Anti-Inflammatory Mechanism of Anti-TNF-α.
Pathway Analysis of Skin from Psoriasis Patients after Adalimumab Treatment Reveals New Early Events in the Anti-Inflammatory Mechanism of Anti-TNF-α.
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DOI：
10.1371/journal.pone.0167437
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Iversen L
中科院分区：
文献类型：
--
作者：
Langkilde A;Olsen LC;Sætrom P;Drabløs F;Besenbacher S;Raaby L;Johansen C;Iversen L
银屑病是一种慢性皮肤炎症性疾病。免疫发病机制是T细胞、树突状细胞和表皮之间复杂的相互作用，其中T细胞和树突状细胞维持皮肤炎症。抗肿瘤坏死因子（抗TNF）-α药物已被批准用于治疗包括银屑病在内的一系列炎症性疾病，但抗TNF-α在银屑病皮损中的抗炎机制尚未完全了解。我们使用生物信息学工具研究银屑病患者抗TNF-α抗体治疗后皮肤的早期事件。我们使用Human Gene 1.0 ST Array分析了抗TNF-α药物阿达木单抗治疗开始前以及治疗开始后4天和14天从银屑病患者中采集的穿刺活检组织中的基因表达。使用来自大卫Bioinformatics Resources的Functional Annotation Tool通过基因集富集分析来分析基因表达。通过京都基因和基因组百科全书（KEGG）图表上的Pathview软件包可视化最丰富的途径。分析显示阿达木单抗治疗后银屑病新发极早期事件。其中一些事件在较长时间的抗TNF-α治疗后出现临床和组织学变化时进行了描述，表明抗TNF-α治疗对基因表达的影响在临床和组织学变化之前很早就出现了。将银屑病患者活检的微阵列数据与通路分析相结合，使我们能够将体外发现整合到可能在体内重要的机制的鉴定中。此外，这些结果可能反映了抗TNF-α治疗的主要效应，而临床和组织学变化后的基因表达变化研究可能反映了与皮肤愈合相关的继发性变化。
Psoriasis is a chronic cutaneous inflammatory disease. The immunopathogenesis is a complex interplay between T cells, dendritic cells and the epidermis in which T cells and dendritic cells maintain skin inflammation. Anti-tumour necrosis factor (anti-TNF)-α agents have been approved for therapeutic use across a range of inflammatory disorders including psoriasis, but the anti-inflammatory mechanisms of anti-TNF-α in lesional psoriatic skin are not fully understood. We investigated early events in skin from psoriasis patients after treatment with anti-TNF-α antibodies by use of bioinformatics tools. We used the Human Gene 1.0 ST Array to analyse gene expression in punch biopsies taken from psoriatic patients before and also 4 and 14 days after initiation of treatment with the anti-TNF-α agent adalimumab. The gene expression was analysed by gene set enrichment analysis using the Functional Annotation Tool from DAVID Bioinformatics Resources. The most enriched pathway was visualised by the Pathview Package on Kyoto Encyclopedia of Genes and Genomes (KEGG) graphs. The analysis revealed new very early events in psoriasis after adalimumab treatment. Some of these events have been described after longer periods of anti-TNF-α treatment when clinical and histological changes appear, suggesting that effects of anti-TNF-α treatment on gene expression appear very early before clinical and histological changes. Combining microarray data on biopsies from psoriasis patients with pathway analysis allowed us to integrate in vitro findings into the identification of mechanisms that may be important in vivo. Furthermore, these results may reflect primary effect of anti-TNF-α treatment in contrast to studies of gene expression changes following clinical and histological changes, which may reflect secondary changes correlated to the healing of the skin.
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Goldminz AM;Suárez-Fariñas M;Wang AC;Dumont N;Krueger JG;Gottlieb AB
通讯作者：
Gottlieb AB
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