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非侵入性评估生物治疗对寻常型银屑病患者皮肤表面蛋白的影响。

Non-Invasive Assessment of Skin Surface Proteins of Psoriasis Vulgaris Patients in Response to Biological Therapy.

机构信息

Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee, 12618 Tallinn, Estonia.

FibroTx LLC., Mäealuse 4, 12618 Tallinn, Estonia.

出版信息

Int J Mol Sci. 2023 Nov 13;24(22):16248. doi: 10.3390/ijms242216248.

Abstract

Measurements of skin surface biomarkers have enormous value for the detailed assessment of skin conditions, both for clinical application and in skin care. The main goals of the current study were to assess whether expression patterns of skin surface hBD-1, hBD-2, IL-1α, CXCL-1, and CXCL-8, examples of proteins known to be involved in psoriasis pathology, are associated with disease severity and whether expression patterns of these proteins on the skin surface can be used to measure pharmacodynamic effects of biological therapy. In this observational study using transdermal analysis patch (TAP), levels of skin surface IL-1α, hBD-1, hBD-2, CXCL-1/2, and CXCL-8 of psoriasis vulgaris (PV) patients over biological therapy were assessed. The Psoriasis Area Severity Index (PASI) and local score for erythema, induration, and desquamation were determined from the exact same skin area as FibroTx TAP measurements. Thirty-seven adult PV patients were included, of which twenty-three were subjected to anti-TNF-α, seven to anti-IL-17A, and seven to anti-IL12/IL-23 therapy. Significantly higher levels of hBD-1, hBD-2, CXCL-1/2, and CXCL-8 were detected on lesional skin compared to the non-lesional skin of the PV patients. In contrast, lower levels of IL-1α were found in lesional skin compared to non-lesional skin. In addition, we observed that the biomarker expression levels correlate with disease severity. Further, we confirmed that changes in the expression levels of skin surface biomarkers during biological therapy correlate with treatment response. Biomarker expression patterns in response to treatment differed somewhat between treatment subtypes. We observed that, in the case of anti-TNF-α therapy, an increase after a steady decrease in the expression levels of CXCL-1/2 and CXCL-8 occurred before the change in clinical scores. Moreover, response kinetics of skin surface proteins differs between the applied therapies-hBD2 expression responds quickly to anti-IL-17A therapy, CXCL-1/2 to anti-IL-12/23, and levels of CXCL-8 are rapidly down-regulated by IL-17A and IL-12/23 therapy. Our findings confirm that the skin surface hBD-2, IL-1α, CXCL-1/2, and CXCL-8 are markers for the psoriasis severity. Further, data obtained during this study give the basis for the conclusion that skin surface proteins CXCL-1/2 and CXCL-8 may have value as therapeutic biomarkers, thus confirming that measuring the 'molecular root' of inflammation appears to have value in scoring disease severity on its own.

摘要

皮肤表面生物标志物的测量对于皮肤状况的详细评估具有巨大的价值,无论是在临床应用还是在皮肤护理方面。本研究的主要目的是评估皮肤表面 hBD-1、hBD-2、IL-1α、CXCL-1 和 CXCL-8 的表达模式是否与疾病严重程度相关,这些蛋白质是已知参与银屑病发病机制的蛋白质,以及这些蛋白质在皮肤表面的表达模式是否可用于测量生物治疗的药效。在这项使用透皮分析贴(TAP)的观察性研究中,评估了接受生物治疗的寻常型银屑病(PV)患者的皮肤表面 IL-1α、hBD-1、hBD-2、CXCL-1/2 和 CXCL-8 水平。从与 FibroTx TAP 测量相同的皮肤区域确定银屑病面积严重程度指数(PASI)和红斑、硬结和脱屑的局部评分。纳入 37 名成年 PV 患者,其中 23 名接受抗 TNF-α、7 名接受抗 IL-17A 和 7 名接受抗 IL12/IL-23 治疗。与 PV 患者的非病变皮肤相比,病变皮肤上检测到 hBD-1、hBD-2、CXCL-1/2 和 CXCL-8 的水平明显更高。相反,病变皮肤中 IL-1α 的水平低于非病变皮肤。此外,我们观察到生物标志物表达水平与疾病严重程度相关。此外,我们证实生物治疗期间皮肤表面生物标志物表达水平的变化与治疗反应相关。治疗反应的生物标志物表达模式在不同的治疗亚型之间存在差异。我们观察到,在抗 TNF-α治疗中,在 CXCL-1/2 和 CXCL-8 的表达水平稳定下降后,出现了表达水平的增加,然后才出现临床评分的变化。此外,应用疗法之间的皮肤表面蛋白的反应动力学不同-hBD2 表达对抗 IL-17A 治疗反应迅速,CXCL-1/2 对抗 IL-12/23,CXCL-8 水平很快被 IL-17A 和 IL-12/23 治疗下调。我们的发现证实,皮肤表面 hBD-2、IL-1α、CXCL-1/2 和 CXCL-8 是银屑病严重程度的标志物。此外,本研究获得的数据为以下结论提供了依据:皮肤表面蛋白 CXCL-1/2 和 CXCL-8 可能具有治疗生物标志物的价值,从而证实测量炎症的“分子根源”本身似乎对评分疾病严重程度具有价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/897b/10671061/7d1b7c60549e/ijms-24-16248-g001.jpg

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