Zhang Jialu, Li Zekun, Liu Guoqing, Yao Wanru, Ai Di, Li Zhengping, Chen Zhenping, Wu Runhui
Department of Hematology Center, National Key Clinical Discipline of Pediatric Hematology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Department of Clinical Laboratory Center, National Key Clinical Discipline of Pediatric Hematology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Transl Pediatr. 2024 Dec 31;13(12):2110-2117. doi: 10.21037/tp-24-300. Epub 2024 Dec 27.
The production of inhibitors is a serious complication that can arise during coagulation factor replacement therapy for hemophilia A (HA). The primary therapeutic strategy to eliminate inhibitors is immune tolerance induction (ITI), which is known to be an extremely challenging, prolonged, and costly treatment. With the widespread use of RNA sequencing (RNA-seq) to analyze differentially expressed genes (DEGs) across various treatment outcomes, there is potential for predicting ITI outcomes. This study aims to use RNA-seq to test differently expressed genes in different outcomes of ITI treatment for HA patients with high-titer inhibitor (HAI), to explore its prediction possibility.
RNA-seq was employed to screen and compare the DEGs between patients in the Success group and those in the Failure group, based on ITI clinical outcomes. DEGs were subjected to Gene Ontology (GO) analysis and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.
Thirteen analyzable HAI cases were collected, comprising seven in the Success group and six in the Failure group. Blood samples were taken before and after ITI. RNA-seq was applied to all samples to screen for expressed genes. In the Success group, a total of 4,967 messenger RNA (mRNA) transcripts were differentially expressed between pre-ITI and post-ITI, with 2,865 being up-regulated and 2,102 down-regulated. In the Failure group, 515 mRNA transcripts were expressed either before or after ITI, showing up-regulation in 68.7% (354/515) and down-regulation in 31.3% (161/515).
The increased expression of genes which related to immune system activation suggests a possibly favorable therapeutic outcome of ITI. Future studies should test with a larger cohort to validate these findings.
抑制剂的产生是甲型血友病（HA）凝血因子替代治疗期间可能出现的严重并发症。消除抑制剂的主要治疗策略是免疫耐受诱导（ITI），这是一种极具挑战性、耗时且成本高昂的治疗方法。随着RNA测序（RNA-seq）广泛用于分析不同治疗结果中的差异表达基因（DEG），预测ITI结果具有可能性。本研究旨在利用RNA-seq检测高滴度抑制剂（HAI）的HA患者ITI治疗不同结果中的差异表达基因，以探索其预测可能性。
基于ITI临床结果，采用RNA-seq筛选并比较成功组和失败组患者之间的DEG。对DEG进行基因本体（GO）分析和京都基因与基因组百科全书（KEGG）通路富集分析。
收集了13例可分析的HAI病例，其中成功组7例，失败组6例。在ITI前后采集血样。对所有样本应用RNA-seq筛选表达基因。在成功组中，ITI前和ITI后共有4967个信使核糖核酸（mRNA）转录本差异表达，其中2865个上调，2102个下调。在失败组中，515个mRNA转录本在ITI前后表达，68.7%（354/515）上调，31.3%（161/515）下调。
与免疫系统激活相关基因表达的增加提示ITI可能有良好的治疗结果。未来研究应以更大的队列进行验证这些发现。
