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阻断白细胞介素-13 信号通路可改善中重度特应性皮炎患者的皮肤屏障功能和生物学特性。

Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis.

机构信息

Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Laboratory for Analytical Chemistry, Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia.

出版信息

Br J Dermatol. 2024 Aug 14;191(3):344-350. doi: 10.1093/bjd/ljae138.

DOI:10.1093/bjd/ljae138
PMID:38531691
Abstract

BACKGROUND

Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab - a monoclonal antibody that neutralizes IL-13 - reduces inflammation and clinical disease activity, less is known about its effects on barrier function.

OBJECTIVES

To characterize the effects of tralokinumab treatment on skin barrier function.

METHODS

Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor content, histopathological characteristics, biomarker expression and microbiome composition were evaluated in lesional, nonlesional and sodium lauryl sulfate-irritated skin of 16 patients with AD over the course of 16 weeks of tralokinumab treatment.

RESULTS

All clinical severity scores decreased significantly over time. At week 16, mean TEWL in target lesions decreased by 33% (P = 0.01) and SCH increased by 58% (P = 0.004), along with a histological reduction in spongiosis (P = 0.003), keratin 16 expression and epidermal thickness (P = 0.001). In parallel, there was a significant decrease in several barrier dysfunction-associated and proinflammatory proteins such as fibronectin (P = 0.006), CCL17/TARC (P = 0.03) and IL-8 (P = 0.01), with significant changes seen as early as week 8. Total bacterial load and Staphylococcus aureus abundance were significantly reduced from week 2.

CONCLUSIONS

Tralokinumab treatment improved skin physiology, epidermal pathology and dysbiosis, further highlighting the pleiotropic role of IL-13 in AD pathogenesis.

摘要

背景

白细胞介素(IL)-13 是特应性皮炎(AD)炎症和屏障功能障碍的关键驱动因素。虽然有大量证据表明,中和 IL-13 的单克隆抗体特利鲁单抗可减轻炎症和临床疾病活动,但对其对屏障功能的影响知之甚少。

目的

描述特利鲁单抗治疗对皮肤屏障功能的影响。

方法

在 16 例 AD 患者的病变、非病变和十二烷基硫酸钠刺激皮肤中,评估特利鲁单抗治疗 16 周过程中经表皮水分丢失(TEWL)、角质层水分(SCH)、天然保湿因子含量、组织病理学特征、生物标志物表达和微生物组组成。

结果

所有临床严重程度评分随时间显著降低。在第 16 周,目标病变处的平均 TEWL 降低了 33%(P = 0.01),SCH 增加了 58%(P = 0.004),海绵形成减少(P = 0.003),角蛋白 16 表达和表皮厚度减少(P = 0.001)。与此同时,与屏障功能障碍和促炎蛋白相关的几种蛋白如纤维连接蛋白(P = 0.006)、CCL17/TARC(P = 0.03)和 IL-8(P = 0.01)的表达显著降低,在第 8 周就可见到显著变化。从第 2 周开始,总细菌负荷和金黄色葡萄球菌丰度显著降低。

结论

特利鲁单抗治疗改善了皮肤生理学、表皮病理学和微生态失调,进一步强调了 IL-13 在 AD 发病机制中的多效作用。

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