Zhonghua Yu Fang Yi Xue Za Zhi. 2026 Sep 6;60(9):1447-1456. doi: 10.3760/cma.j.cn112150-20250903-00852.
ABSTRACT
Objective: To investigate the expression levels of programmed death receptor-1 (PD-1) and its ligand (programmed death-ligand 1, PD-L1) in CD4+T cells from peripheral blood of children with Kawasaki disease, analyzes their correlation with inflammatory indicators such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII), and further evaluate the diagnostic value of these indicators for Kawasaki disease. Methods: In this cross-sectional study, 57 children with Kawasaki disease and 44 children with febrile illness diagnosed at the Affiliated Children’s Hospital of Nanjing Medical University between November 2024 and September 2025 were enrolled, along with 49 healthy children from the hospital’s physical examination center as controls. Flow cytometry was used to measure the expression levels of PD-1 and PD-L1 in CD4+T cells from peripheral blood of the children. Spearman correlation analysis was applied to assess the correlation between the proportion of CD4+PD-1+T and CD4+PD-L1+T cells and various inflammatory indicators. Binary logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to calculate the optimal cut-off value, sensitivity, and specificity for diagnosing Kawasaki disease. Data are presented as median (interquartile range), denoted as M (Q1,Q3). Results: No significant differences were observed among the three groups in terms of gender, age, or duration of fever [gender: χ²=0.65, P=0.721;age: 4.00 (3.00, 5.00) years vs.3.00 (2.00, 5.50) years vs.3.00 (1.00, 6.00) years, H=0.44, P=0.804;duration of fever[ M (Q1,Q3)]: 4.00 (1.00, 6.00) d vs.4.00 (3.00, 5.00) d,U=976.00, P=0.204]. The inflammatory indicators (NLR, PLR, SII) and the proportion of CD4+PD-1+T and CD4+PD-L1+T cells in peripheral blood were significantly higher in Kawasaki disease group than in the healthy and febrile groups [NLR: 2.78 (1.16, 4.45) vs.0.81(0.52, 1.04) vs.0.86 (0.35, 2.14), H=40.76, P<0.01; PLR: 111.10 (85.90, 169.10) vs.85.22 (67.60, 107.30) vs.86.94 (59.20, 125.60), H=11.74, P<0.01; SII: 894 (484, 1 543) vs.231.60 (137.10, 363.20) vs.242.80 (90.05, 515.60), H=51.54, P<0.01; CD4+PD-1+T%: 5.46% (3.36%, 8.00%) vs.2.68% (1.88%, 3.97%) vs.3.52% (2.19%, 4.73%), H=32.58, P<0.01; CD4+PD-L1+T%: 8.17% (4.30%, 12.46%) vs.1.57% (1.05%, 2.85%) vs.1.74% (1.20%, 3.22%), H=67.30, P<0.01]. Spearman correlation analysis revealed that the expression ratio of CD4+PD-1+T cells in peripheral blood of the children was positively correlated with NLR, PLR, and SII (r=0.397, P=0.002; r=0.297, P=0.025; r=0.349,P=0.008), and the proportion of CD4+PD-L1+T cells was also positively correlated with the same markers (r=0.330, P=0.012; r=0.289, P=0.029; r=0.382, P=0.003).ROC analysis for diagnosing KD yielded the following area under the curve (AUC) values for CD4⁺PD-1⁺T cells, CD4⁺PD-L1⁺T cells, NLR, PLR, and SII: (AUC: HC-KD) of 0.79 (95%CI: 0.71-0.88), 0.89 (95%CI: 0.83-0.95), 0.84 (95%CI: 0.76-0.92), 0.67 (95%CI: 0.57-0.77), 0.87 (95%CI: 0.80-0.94); (AUC: FC-KD) were 0.75 (95%CI: 0.66-0.85), 0.90 (95%CI: 0.84-0.96), 0.76 (95%CI: 0.66-0.86), 0.62 (95%CI: 0.50-0.73), 0.81(95%CI: 0.73-0.90).The combination of CD4⁺PD-1⁺T and CD4⁺PD-L1⁺T cell proportions with NLR, PLR, and SII demonstrated high diagnostic performance for pediatric KD, with an AUC (HC-KD) of 0.95 (95%CI: 0.92-0.99), with sensitivity and specificity of 88.1% and 94.1%, respectively; AUC (FC-KD) was 0.97 (95%CI: 0.94-1.00), with sensitivity and specificity of 90.9% and 92.9%, respectively. Conclusion: The proportion of CD4+PD-1+T and CD4+PD-L1+T cells in peripheral blood of Kawasaki disease patients is elevated, closely related to inflammatory markers NLR, PLR, SII, suggesting that PD-1 and PD-L1 are important causes of immune disorder in pediatric Kawasaki disease, possibly playing a significant role in the occurrence of KD. The combined use of these cellular and inflammatory indicators enhances diagnostic accuracy and holds promise for early Kawasaki disease detection.
PMID:42736148 | DOI:10.3760/cma.j.cn112150-20250903-00852
