Frequencies of PD-1 and LAG-3 positive T cells in asthmatic children and their relationship with inflammatory cytokines

Abstract Objectives This study aimed to investigate the expression of programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) on CD4 + and CD8 + T cells in children with asthma and their relationship with Th2-associated inflammatory cytokines (IL-4, IL-5, and IL-13). The goal was to elucidate the potential roles of these immune checkpoint molecules in asthma pathogenesis and severity. Methods A prospective observational study was conducted involving 112 asthmatic children aged 5–15 years and 100 healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated, and flow cytometry was used to analyze the frequencies of PD-1 + and LAG-3 + T cells. Serum levels of IL-4, IL-5, and IL-13 were measured using ELISA. Asthma severity was classified according to the Global Initiative for Asthma (GINA) guidelines, and demographic, clinical, and lung function data were collected. Statistical analyses included Pearson correlation, ROC curve analysis, and logistic regression to assess the diagnostic and prognostic value of PD-1 and LAG-3 expression. Results Asthmatic children, particularly those with moderate-to-severe disease, exhibited significantly higher frequencies of PD-1 + and LAG-3 + T cells compared to healthy controls. Serum levels of IL-4, IL-5, and IL-13 were also elevated in asthmatic children, with the highest levels observed in moderate-to-severe cases. The frequencies of PD-1 + LAG-3 + T cells were positively correlated with IL-13 levels and negatively correlated with lung function parameters, including FVC%, FEV1%, and PEF%. ROC curve analysis demonstrated that CD4 + PD-1 + LAG-3 + T cells had superior diagnostic performance for moderate-to-severe asthma. Logistic regression identified CD4 + LAG-3 + PD-1 + , and IL-13 as independent risk factors for moderate-to-severe asthma. Conclusions The elevated frequencies of PD-1 and LAG-3 on T cells in asthmatic children, particularly in those with moderate-to-severe disease, suggested that these immune checkpoint molecules play a critical role in asthma pathogenesis and severity. These findings highlighted the potential of PD-1 and LAG-3 as biomarkers for asthma severity and therapeutic targets, offering new avenues for immune modulation in pediatric asthma management.