150 - ELUCIDATING IMMUNE CELL METABOLIC SHIFTS IN KAWASAKI DISEASE THROUGH SINGLE-CELL MULTI-OMICS ANALYSIS

BACKGROUND/

Aim:

While our previous research highlighted a shared gene program in neutrophils between Kawasaki Disease (KD) and MIS-C (Circulation, 2023, PMID: 37905415), the broader impact on various circulating immune cells, particularly in immune metabolism, remains unclear. This study leverages single-cell multi-omics to uncover alterations in immune cell metabolism in KD.

Methods:

Single-cell ATAC-seq was performed on 21 KD samples, including 3 non-KD (control) and 18 acute KD patients, to chart the single-cell epigenetic landscape and uncover regulatory pathways affecting immune metabolism in KD. Cells underwent rigorous quality control based on transcription start site (TSS) scores and the number of fragments (nFrag). We employed Latent Semantic Indexing and Uniform Manifold Approximation and Projection (UMAP) for cell clustering, focusing on T cells for further analysis.

Results:

Analysis of 18,123 cells post-quality control revealed five distinct cell clusters. Four subclusters were discerned within T cells, including CD4+ and CD8+ T cells. Subsequent clustering and Gene Ontology (GO) pathway analysis on CD8+ T cells highlighted a significant upregulation in glucuronate metabolic pathways, particularly cellular glucuronidation (GO:0052695) and glucuronate metabolic process (GO:0019585). Additionally, essential differentially accessible genes (DAGs) such as UGT1A8 and UGT1A10, which play a crucial role in immune metabolism alterations within CD8+ T cell subclusters, were identified.

Conclusion:

Our findings reveal significant alterations in glucuronate metabolism and immune cell metabolism in KD. This study not only enhances our understanding of KD's pathophysiology but also opens avenues for developing targeted treatments, showcasing the power of single-cell multi-omics in unraveling complex disease processes.