Immunocyte phenotypes and childhood disease susceptibility: insights from bidirectional Mendelian randomization and implications for immunomodulatory therapies.

Immune cells are essential for maintaining immune homeostasis during childhood and influence both growth and disease susceptibility. However, the causal relationships between immunocyte phenotypes and childhood diseases remain unclear. This study employed a two-sample Mendelian Randomization (MR) analysis to assess causal associations between 731 immunocyte phenotypes and four major childhood diseases: childhood obesity, childhood absence epilepsy, childhood asthma, and childhood allergies. Genome-wide association study (GWAS) data were used, and stringent instrumental variable (IV) selection and multiple sensitivity analyses, including MR-Egger, weighted median, and leave-one-out tests, were applied to validate the robustness of the results. Significant associations were identified between specific T cell, monocyte, and B cell phenotypes and childhood diseases. Notably, CD8bright T cells and CD19 + B cells were positively correlated with childhood obesity, while monocyte subtypes were strongly associated with asthma pathophysiology. Reverse MR analysis indicated no significant causal effects of childhood diseases on immune phenotypes, except for negative associations between childhood asthma and TCRgd AC, and childhood allergy and CD28 + CD45RA + CD4 + cells. These findings highlight the critical role of immune dysregulation in childhood disease etiology and suggest potential targets for immunomodulatory therapies. Understanding these immune-disease interactions may inform novel pharmacological interventions, particularly in immune-mediated disorders such as asthma and obesity. Further research into immune-targeted therapies could enhance treatment strategies for pediatric conditions associated with chronic inflammation and immune dysfunction.