Serum inflammatory biomarkers associated with disease severity and response to dupilumab treatment in bullous pemphigoid: A cluster analysis

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Abstract

Background

Dupilumab, a novel therapy targeting the T helper (Th) 2-mediated inflammation, is showing clinical benefits in treating bullous pemphigoid (BP). However, limited research investigated the serum biomarkers that reflect the inflammation alterations throughout the disease course.

Objectives

To explore the changes of the serum inflammatory biomarkers under dupilumab therapy in BP and establish their correlations with disease severity and clinical outcomes.

Methods

This exploratory study evaluated serum samples from 40 patients with BP at baseline, 30 of these patients following 16-week dupilumab therapy, and 20 senior healthy controls. Serum levels of 29 cytokines and chemokines were quantified using the Magnetic Luminex Assay.

Results

Two distinct clusters based on serum inflammatory profiles were identified. The first cluster, characterized by elevated levels of inflammatory activation, exhibited worse disease severity and poorer remission outcomes. Following the 16-week dupilumab therapy regimen, a significant suppression of Th2-mediated inflammation in the serum was observed, alongside a relative upregulation of Th1 responses. Patients treated with adjuvant systemic steroids exhibited an enhanced suppression of B cell activating factor compared to those receiving dupilumab alone. Significant correlations were unveiled between Th2 biomarkers and clinical scores, eosinophil counts, and anti-BP180 immunoglobulin G levels. Baseline levels of CCL18, Periostin, interleukin (IL)-6, and IL-16 constitute an optimal combination to distinguish between inflammatory clusters.

Conclusions

Cluster analysis of serum inflammatory biomarkers provided novel insights into the heterogeneity of the inflammation profiles in BP. Baseline levels of CCL18, Periostin, IL-6, IL-16 emerged as effective predictors for disease severity and therapy response to dupilumab.
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与大疱性类天疱疮疾病严重程度和对杜匹单抗治疗反应相关的血清炎症生物标志物:聚类分析
背景:Dupilumab是一种针对T辅助细胞(Th)2介导的炎症的新型疗法,在治疗大疱性类天疱疮(BP)方面显示出临床疗效。然而,对反映整个病程中炎症变化的血清生物标志物的研究却很有限:目的:探讨杜匹单抗治疗大疱性类天疱疮时血清炎症生物标志物的变化,并确定其与疾病严重程度和临床结果的相关性:这项探索性研究评估了 40 名 BP 患者基线时的血清样本、其中 30 名患者接受 16 周杜匹单抗治疗后的血清样本以及 20 名资深健康对照者的血清样本。使用 Magnetic Luminex Assay 对 29 种细胞因子和趋化因子的血清水平进行了量化:结果:根据血清炎症特征确定了两个不同的群组。第一组的特点是炎症激活水平升高,疾病严重程度更严重,缓解效果更差。在接受为期16周的dupilumab治疗后,观察到血清中Th2介导的炎症明显抑制,同时Th1反应相对上调。与单独接受杜比单抗治疗的患者相比,接受辅助性全身类固醇治疗的患者表现出更强的B细胞活化因子抑制能力。Th2生物标记物与临床评分、嗜酸性粒细胞计数和抗BP180免疫球蛋白G水平之间存在显著相关性。CCL18、Periostin、白细胞介素(IL)-6和IL-16的基线水平是区分炎症集群的最佳组合:血清炎症生物标志物的聚类分析为了解血压炎症特征的异质性提供了新的视角。CCL18、Periostin、IL-6、IL-16的基线水平可有效预测疾病的严重程度和对dupilumab的治疗反应。
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