Peripheral immune imbalance in pediatric fulminant myocarditis revealed by single-cell sequencing and plasma proteomics.

Abstract

The precise pathological immune subsets and molecular changes in myocarditis, especially fulminant myocarditis (FM), have not been elucidated. We present a systemic analysis of immunological signatures and cell communications from pediatric PBMCs during the acute and recovery phases of FM using scRNA-seq. The peripheral immune profile in acute FM exhibited significant dysregulation in the proportion and function of immune cells. Several unique cell types, regulatory B cells, MAIT cells, adaptive NK cells, and CD8⁺Tpex cells, were identified in peripheral blood. Transcriptomic analysis revealed elevated expression of chemokine receptor CXCR4 and S100A family genes across nearly all cell types in the FM acute phase, as well as MHC-II molecules in antigen-presenting cells. TCR and BCR analysis showed remarkable clonal amplification and skewed V gene usage. Ligand receptor analysis highlighted active communication between myeloid cells and other immune cells. Furthermore, plasma proteomics analysis identified 36 differentially expressed proteins that interact with peripheral immune cells. Notably, anti-inflammation factors IL-10 and TGFB1 demonstrated significant potential in regulating the activity of downstream target genes involved in the immune response of peripheral immune cells. These findings enhance the understanding of the immune landscape of pediatric FM and provide valuable insights for developing potential diagnostic and therapeutic strategies.