Wang Yu, Wu Yuemeng, Gu Chaoying, Wang Shangshang, Yin Huibin, Zhu Ronghui, Wang Ce, Li Zheng, Yao Xu, Li Wei
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, PR China.
Department of Biostatistics, School of Public Health, and The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, PR China.
J Dermatol Sci. 2023 Sep;111(3):83-92. doi: 10.1016/j.jdermsci.2023.06.002. Epub 2023 Jun 8.
Few studies have explored transcriptome of the peripheral blood mononuclear cells (PBMCs) of atopic dermatitis (AD). Parameters for prediction of the efficacy of dupilumab in AD remain obscure.
To explore transcriptome signature of the PBMCs from Chinese AD patients and the usage in predication for the efficacy of dupilumab.
A total of 56 moderate-to-severe adult AD patients were enrolled and followed up for 16 week-dupilumab treatment. PBMCs samples were collected at baseline and 16 weeks after dupilumab treatment. Thirty-five patients were subjected to RNA-sequencing. Weighted gene co-expression network analysis (WGCNA) was used to find genes for prediction of dupilumab efficacy, which was validated in the rest 21 AD patients. Another 30 healthy individuals were enrolled and subjected to RNA-sequencing as healthy controls.
Upregulation of the T helper (Th) 2/Th22 pathway, Th17 antimicrobial genes, and natural T-regulatory cell abundance in the PBMCs of AD cases was observed, whereas TGF-β signaling and NK-cell signaling were decreased. Dupilumab treatment reversed the increase in the expression of Th2 cytokine receptors. WGCNA identified two immune-related modules that were correlated significantly with the efficacy of dupilumab. Hub gene MAP2K3 and UBE2L3 of these two modules demonstrated potential predictive ability for efficacy in the RNA-sequencing group by Spearman correlation, ROC analysis, and regression analysis, which was further validated in additional 21 AD cases.
We firstly revealed the molecular phenotype of PBMCs in Chinese patients with AD, and uncovered two molecules that might be useful for prediction of the efficacy of dupilumab.
很少有研究探索特应性皮炎（AD）患者外周血单个核细胞（PBMC）的转录组。预测度普利尤单抗治疗AD疗效的参数仍不明确。
探索中国AD患者PBMC的转录组特征及其在预测度普利尤单抗疗效中的应用。
共纳入56例中重度成年AD患者，接受度普利尤单抗治疗16周并进行随访。在基线期和度普利尤单抗治疗16周后采集PBMC样本。35例患者进行RNA测序。采用加权基因共表达网络分析（WGCNA）寻找预测度普利尤单抗疗效的基因，并在其余21例AD患者中进行验证。另纳入30名健康个体进行RNA测序作为健康对照。
观察到AD患者PBMC中辅助性T细胞（Th）2/Th22通路、Th17抗菌基因上调，天然调节性T细胞丰度增加，而转化生长因子-β信号通路和自然杀伤细胞信号通路减少。度普利尤单抗治疗逆转了Th2细胞因子受体表达的增加。WGCNA识别出两个与度普利尤单抗疗效显著相关的免疫相关模块。通过Spearman相关性分析、ROC分析和回归分析，这两个模块的枢纽基因MAP2K3和UBE2L3在RNA测序组中显示出对疗效的潜在预测能力，并在另外21例AD病例中得到进一步验证。
我们首次揭示了中国AD患者PBMC的分子表型，并发现了两个可能有助于预测度普利尤单抗疗效的分子。
