Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.