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乌司奴单抗治疗严重特应性皮炎:下调 T 辅助细胞 2/22 的表达。

Ustekinumab treatment in severe atopic dermatitis: Down-regulation of T-helper 2/22 expression.

机构信息

Department of Dermatology, Division of Immunology, Allergy, and Infectious Diseases, Medical University of Vienna, Vienna, Austria.

Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.

出版信息

J Am Acad Dermatol. 2017 Jan;76(1):91-97.e3. doi: 10.1016/j.jaad.2016.07.047. Epub 2016 Oct 13.

Abstract

BACKGROUND

It has recently been suggested that patients with moderate to severe atopic dermatitis (AD) may profit from anti-interleukin (IL)-12/-23 p40 therapy.

OBJECTIVE

We sought to assess the immunologic effects of ustekinumab treatment on AD skin and to correlate them with the clinical efficacy of this drug.

METHODS

We investigated the course of 3 patients with severe AD who were administered 45 mg of subcutaneous ustekinumab over a period of 16 weeks. Clinical scores and skin biopsy specimens, taken at baseline and at week 8, were used to assess changes in disease severity.

RESULTS

All patients showed a gradual improvement of the disease, achieving a 50% reduction in the Eczema Area and Severity Index score by week 16. Immunohistology of skin biopsy specimens revealed a significant decrease in the degree of epidermal hyperplasia/proliferation and the number of infiltrating dermal T cells, dendritic cells, and mast cells after treatment. Using quantitative real-time polymerase chain reaction of lesional skin, we found a clear reduction of T-helper 2-/22-associated molecules after therapy.

LIMITATIONS

The small number of patients (n = 3) limits efficacy analysis and warrants prospective placebo-controlled studies in larger patient cohorts.

CONCLUSION

Blocking IL-12/-23 p40 could be beneficial for a subgroup of patients with severely infiltrated AD.

摘要

背景

最近有人提出,中重度特应性皮炎(AD)患者可能受益于抗白细胞介素(IL)-12/-23 p40 治疗。

目的

我们旨在评估乌司奴单抗治疗对 AD 皮肤的免疫效应,并将其与该药物的临床疗效相关联。

方法

我们研究了 3 名接受 45 mg 皮下乌司奴单抗治疗的重度 AD 患者,治疗时间为 16 周。使用临床评分和基线及第 8 周的皮肤活检标本来评估疾病严重程度的变化。

结果

所有患者的疾病均逐渐改善,到第 16 周时 Eczema Area and Severity Index 评分降低了 50%。皮肤活检标本的免疫组织化学显示,治疗后表皮过度增生/增殖和浸润真皮的 T 细胞、树突状细胞和肥大细胞数量明显减少。对皮损皮肤进行实时定量聚合酶链反应,我们发现治疗后 T 辅助 2/22 相关分子明显减少。

局限性

患者数量较少(n=3)限制了疗效分析,需要在前瞻性安慰剂对照研究中纳入更大的患者队列。

结论

阻断 IL-12/-23 p40 可能对浸润严重的 AD 亚组患者有益。

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