Longitudinal peripheral blood immune profiling reveals dynamic changes of five major immune cell lineages and their clinical associations in pediatric scrub typhus

Objective To investigate the dynamic changes of five major peripheral blood immune cell lineages during acute scrub typhus in children and their association with disease severity. Methods A total of 141 children with clinically diagnosed scrub typhus were enrolled, including 100 mild and 41 severe cases. All children provided pretreatment immune samples, and 110 children with repeated post-treatment sampling contributed 299 observations to longitudinal immune analyses. Peripheral blood was collected at multiple time points, and the proportions and phenotypes of dendritic cells (DCs), monocytes, CD4 + T cells, CD8 + T cells, and B cells were analyzed by multicolor flow cytometry. Linear mixed-effects models were used to assess the dynamic changes of immune parameters over the disease course, and Spearman partial correlation analysis was performed to evaluate the associations between immune parameters and clinical indices. Results Over the disease course, the proportion of HLA-DR + monocytes increased most rapidly (FDR q = 0.003), and the proportions of DCs, CD4 + T cells, and CD8 + T cells also increased significantly (FDR q < 0.05). CD8 + T cells showed a reduction in naive subsets and an expansion of effector memory and TEMRA subsets. Among B cells, double-negative B cells decreased, while HLA-DR + B cells and IgM memory B cells increased (FDR q < 0.05). Severe cases had significantly higher proportions of monocytes and B cells, but lower proportions of DCs, CD4 + T cells, and CD8 + T cells compared with mild cases (FDR q < 0.05). The proportion of activated CD8 + T cells was positively correlated with lactate dehydrogenase and D-dimer, and negatively correlated with platelet count (all FDR q < 0.001). After treatment, HLA-DR + B cells and several monocyte subsets increased significantly (FDR q < 0.05). Conclusion This study systematically delineates the dynamic evolution of five major immune cell lineages during acute scrub typhus in children, describing immune alterations including a rapid increase of HLA-DR + monocytes and a differentiation shift of CD8 + T cells toward an effector memory phenotype. It also demonstrates significant associations between activated CD8 + T cells and tissue injury as well as coagulation dysfunction. These findings provide novel longitudinal evidence for understanding the immunopathogenesis of scrub typhus in children.