Accumulating evidence indicates that severe viral infections in a subset of children may result from dysregulated antiviral pathways caused by inborn errors of immunity (IEI). Based on this central hypothesis, we aim to establish a national research cohort of Taiwanese children with severe viral infections. By integrating detailed clinical manifestations with immunophenotypic analyses, we systematically investigate the molecular and genetic mechanisms underlying disease severity.

Identification of Inborn Errors of Immunity Using Sequencing and Next-Generation Sequencing Technologies

Our previous research has demonstrated that severe enteroviral encephalitis can be caused by functional defects in TLR3 signaling (Kuo, Journal of Clinical Immunology, 2022). In the context of chronic mucocutaneous candidiasis (CMC), both prior literature and our recent work indicate that abnormalities in STAT1 or genes involved in the Th17 pathway are closely associated with disease susceptibility (Lei, Journal of Clinical Immunology, 2024). These findings support the concept that specific genetic defects confer susceptibility to specific infectious diseases.

Building on this foundation, we will employ next-generation sequencing (NGS) combined with functional validation to identify pathogenic variants in Taiwanese children with severe viral infections. Our goal is to link genetic variants to dysregulated immune pathways and to develop translational genetic diagnostic tools and precision therapeutic strategies. Ultimately, this research is expected to have a substantial clinical impact on disease prevention, prognostic stratification, and targeted treatment.