Department of Dermatology, Peking University First Hospital, Beijing, China; National Clinical Research Center for Skin and Immune Diseases, Beijing, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China; National Medical Products Administration Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China.
Department of Dermatology, Peking University First Hospital, Beijing, China; National Clinical Research Center for Skin and Immune Diseases, Beijing, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China; National Medical Products Administration Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China.
J Dermatol Sci. 2024 Oct;116(1):24-33. doi: 10.1016/j.jdermsci.2024.09.003. Epub 2024 Sep 18.
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.
To explore the changes of the serum inflammatory biomarkers under dupilumab therapy in BP and establish their correlations with disease severity and clinical outcomes.
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.
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.
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.
靶向 T 辅助（Th）2 介导的炎症的新型疗法度普利尤单抗在治疗大疱性类天疱疮（BP）方面显示出临床益处。然而，关于反映疾病过程中炎症变化的血清生物标志物的研究有限。
探讨度普利尤单抗治疗 BP 患者过程中血清炎症生物标志物的变化，并建立其与疾病严重程度和临床结局的相关性。
本探索性研究评估了 40 例 BP 患者的基线血清样本，其中 30 例患者在 16 周度普利尤单抗治疗后进行了评估，20 例老年健康对照者纳入研究。采用磁珠液相芯片技术定量检测 29 种细胞因子和趋化因子的血清水平。
根据血清炎症谱，确定了两个不同的聚类。第一个聚类表现为炎症激活水平升高，其疾病严重程度更高，缓解结局更差。经过 16 周的度普利尤单抗治疗方案后，观察到血清中 Th2 介导的炎症显著抑制，同时 Th1 反应相对上调。与单独接受度普利尤单抗治疗的患者相比，接受辅助全身皮质类固醇治疗的患者 B 细胞激活因子的抑制作用增强。Th2 生物标志物与临床评分、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、骨膜蛋白、白细胞介素（IL）-6 和 IL-16 的基线水平构成了区分炎症聚类的最佳组合。
血清炎症生物标志物聚类分析为 BP 炎症谱的异质性提供了新的见解。CCL18、骨膜蛋白、IL-6、IL-16 的基线水平是疾病严重程度和度普利尤单抗治疗反应的有效预测指标。
