Cardiovascular

[Expression and significance of PD-1/PD-L1 in CD4+T cells in peripheral blood of children with Kawasaki disease].

TL;DR

The proportion of CD4+PD-1+T and CD4+PD-L1+T cells in peripheral blood of Kawasaki disease patients is elevated and closely related to inflammatory markers NLR, PLR, and SII, suggesting that PD-1 and PD-L1 are important causes of immune disorder in pediatric Kawasaki disease, and their combined use with inflammatory indicators enhances diagnostic accuracy.

Key Findings

CD4+PD-1+T cell proportions were significantly higher in Kawasaki disease children compared to both healthy controls and febrile illness controls.

  • CD4+PD-1+T% in KD group: 5.46% (3.36%, 8.00%) vs. healthy controls: 2.68% (1.88%, 3.97%) vs. febrile controls: 3.52% (2.19%, 4.73%)
  • Kruskal-Wallis H=32.58, P<0.01
  • Measured by flow cytometry in peripheral blood samples
  • Study enrolled 57 KD children, 44 febrile illness children, and 49 healthy controls

CD4+PD-L1+T cell proportions were markedly elevated in Kawasaki disease children compared to both control groups.

  • CD4+PD-L1+T% in KD group: 8.17% (4.30%, 12.46%) vs. healthy controls: 1.57% (1.05%, 2.85%) vs. febrile controls: 1.74% (1.20%, 3.22%)
  • Kruskal-Wallis H=67.30, P<0.01
  • The difference between healthy and febrile controls was minimal compared to KD group
  • Measured by flow cytometry

Inflammatory indicators NLR, PLR, and SII were all significantly higher in the Kawasaki disease group than in healthy and febrile control 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, 1543) vs. 231.60 (137.10, 363.20) vs. 242.80 (90.05, 515.60), H=51.54, P<0.01
  • The three groups did not differ significantly in gender, age, or duration of fever

CD4+PD-1+T cell proportions were positively correlated with all three inflammatory markers (NLR, PLR, SII) in Kawasaki disease patients.

  • Correlation with NLR: r=0.397, P=0.002
  • Correlation with PLR: r=0.297, P=0.025
  • Correlation with SII: r=0.349, P=0.008
  • Assessed by Spearman correlation analysis

CD4+PD-L1+T cell proportions were also positively correlated with all three inflammatory markers (NLR, PLR, SII) in Kawasaki disease patients.

  • Correlation with NLR: r=0.330, P=0.012
  • Correlation with PLR: r=0.289, P=0.029
  • Correlation with SII: r=0.382, P=0.003
  • Assessed by Spearman correlation analysis

CD4+PD-L1+T cells showed the highest individual AUC for diagnosing Kawasaki disease compared to other single markers.

  • AUC for CD4+PD-L1+T cells (HC-KD): 0.89 (95%CI: 0.83-0.95); (FC-KD): 0.90 (95%CI: 0.84-0.96)
  • AUC for CD4+PD-1+T cells (HC-KD): 0.79 (95%CI: 0.71-0.88); (FC-KD): 0.75 (95%CI: 0.66-0.85)
  • AUC for NLR (HC-KD): 0.84 (95%CI: 0.76-0.92); (FC-KD): 0.76 (95%CI: 0.66-0.86)
  • AUC for SII (HC-KD): 0.87 (95%CI: 0.80-0.94); (FC-KD): 0.81 (95%CI: 0.73-0.90)
  • AUC for PLR (HC-KD): 0.67 (95%CI: 0.57-0.77); (FC-KD): 0.62 (95%CI: 0.50-0.73)

The combined use of CD4+PD-1+T and CD4+PD-L1+T cell proportions with NLR, PLR, and SII demonstrated high diagnostic performance for pediatric Kawasaki disease.

  • Combined AUC (HC-KD): 0.95 (95%CI: 0.92-0.99), with sensitivity 88.1% and specificity 94.1%
  • Combined AUC (FC-KD): 0.97 (95%CI: 0.94-1.00), with sensitivity 90.9% and specificity 92.9%
  • These combined values substantially exceeded the AUCs of any individual marker
  • Binary logistic regression and ROC curve analysis were used to calculate optimal cut-off values, sensitivity, and specificity

The three study groups were comparable in gender, age, and duration of fever, supporting the validity of group comparisons.

  • Gender: χ²=0.65, P=0.721
  • Age (years): 4.00 (3.00, 5.00) vs. 3.00 (2.00, 5.50) vs. 3.00 (1.00, 6.00), H=0.44, P=0.804
  • Duration of fever: 4.00 (1.00, 6.00) days vs. 4.00 (3.00, 5.00) days, U=976.00, P=0.204
  • Cross-sectional study conducted November 2024 to September 2025 at Affiliated Children's Hospital of Nanjing Medical University

What This Means

This research suggests that children with Kawasaki disease—a serious inflammatory condition that primarily affects young children and can damage the heart—have significantly higher levels of specific immune checkpoint proteins (PD-1 and PD-L1) on their CD4+ T immune cells compared to both healthy children and children with ordinary fevers. The study measured these proteins in the blood of 57 children with Kawasaki disease, 44 children with fever from other causes, and 49 healthy children. In Kawasaki disease, the proportion of CD4+ T cells carrying PD-L1 was about five times higher than in the other two groups, while PD-1-bearing cells were roughly twice as elevated, suggesting these immune 'checkpoint' molecules play an important role in the abnormal immune response seen in Kawasaki disease. This research also suggests that these immune cell markers are closely linked to standard blood inflammation tests (NLR, PLR, and SII), meaning they likely reflect the same underlying inflammatory process rather than an entirely separate mechanism. Importantly, when the PD-1 and PD-L1 immune cell measurements were combined with the inflammation blood tests, the diagnostic accuracy for Kawasaki disease was very high—correctly identifying roughly 89-91% of true cases and correctly excluding 93-95% of non-cases—outperforming any single test alone. These findings matter because Kawasaki disease is often difficult to distinguish from ordinary childhood fevers, and delayed diagnosis can lead to serious heart complications. This research suggests that measuring PD-1 and PD-L1 on CD4+ T cells, alongside routine inflammation markers, could offer a more reliable blood-based approach to help doctors identify Kawasaki disease earlier. The study also suggests that the PD-1/PD-L1 immune pathway may be a key driver of the immune dysregulation that defines Kawasaki disease, which could open new avenues for understanding and potentially treating the condition.

Have a question about this study?

Citation

Zhang Y, Wu M, Yang D, Zhang Y, Chen H. (2026). [Expression and significance of PD-1/PD-L1 in CD4+T cells in peripheral blood of children with Kawasaki disease].. Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]. https://doi.org/10.3760/cma.j.cn112150-20250903-00852