Sclerotic-type chronic graft-versus-host disease exhibits enrichment of Th1 and TSLP-OX40 cytokines. Sclerotic-type chronic graft-versus-host disease exhibits enrichment of Th1 and TSLP-OX40 cytokines

In this study we performed the first global RNA-seq analysis in pediatric to young-adult patients with sclerotic-type graft-versus-host disease/scGvHD (n=7), age- and sex-matched to 8 healthy controls and 10 patients with atopic dermatitis/AD. Differentially expressed genes (DEGs) were defined based on fold changes/FCH>1.5 and false discovery rate/FDR<0.05 criteria. We found robust and significant Th1 (e.g. CXCR9/10/11, IFNG) and OX40-skewing in ScGvHD (e.g. OX40L, TLSP, IL-33) that sometimes exceeded that in AD and was validated on RT-PCR. Overall design: RNA-seq data was profiled from skin biopsies of 7 pediatric/young-adult patients with sclerotic-type chronic graft-versus-host disease, age- and sex- matched to 10 patients with moderate-to-severe atopic dermatitis (lesional and non-lesional) and 8 healthy controls.

本研究首次针对硬化性移植物抗宿主病（sclerotic-type graft-versus-host disease, scGvHD）的儿科至青年成人患者开展全转录组RNA测序分析，共纳入7例患者，并以年龄、性别匹配的8名健康对照者及10例特应性皮炎（atopic dermatitis, AD）患者作为对照。差异表达基因（Differentially expressed genes, DEGs）的筛选标准为倍数变化（fold changes, FCH）>1.5且错误发现率（false discovery rate, FDR）<0.05。研究发现scGvHD患者体内存在显著且稳定的辅助性T细胞1型（Th1）通路活化（如CXCR9/10/11、IFNG）及OX40通路偏向性活化（如OX40L、TLSP、IL-33），部分指标的表达变化幅度甚至超过AD患者，该结果经逆转录聚合酶链反应（RT-PCR）验证。整体实验设计：本研究的RNA测序数据来源于7例儿科/青年成人硬化性慢性移植物抗宿主病患者的皮肤活检组织，同时纳入年龄、性别匹配的10例中重度特应性皮炎患者（采集其皮损区与非皮损区样本）及8名健康对照者的皮肤活检组织。