ICAM signaling rewires the inflammatory communication network in pediatric gout

The immune regulatory characteristics and core inflammatory signaling networks of pediatric gout have not been fully elucidated. The prevailing view of generalized immune hyperactivation cannot precisely explain the unique immune pathological features of pediatric gout, highlighting an urgent research gap to be addressed.

To clarify the immune regulatory mechanism of pediatric gout, we performed single-cell transcriptomic profiling and systematic cell-cell interaction analysis on peripheral blood samples collected from pediatric gout patients and healthy controls. We comprehensively compared the intercellular communication networks, signaling pathway activities, and molecular expression patterns between the two groups, and focused on the differential inflammatory signaling axes dominating pediatric gout pathogenesis.

Different from the traditional view of global immune hyperactivation, pediatric gout exhibited a highly selective remodeling of circulating immune networks. The ICAM signaling pathway was identified as the most dominant and disease-specific inflammatory axis in pediatric gout. In the immune communication network, platelets served as the major signal-emitting hubs with significantly enhanced signaling activity in patients, while CD14⁺ monocytes acted as the primary signal recipients. Selective upregulation of ICAM1 was detected in CD14⁺ monocytes of pediatric gout patients, which endowed monocytes with strengthened signal -receiving capacity. Notably, other classic immune pathways showed no significant differences between patients and healthy controls.

This study demonstrates that pediatric gout is characterized by directional and selective immune crosstalk rather than universal immune activation. The ICAM-centered inflammatory interactome is the core driver of immune network remodeling in pediatric gout. These findings complement and advance previous single-cell research on adult gout, and identify the ICAM signaling pathway as a novel and promising therapeutic target for the precise clinical intervention of pediatric gout.