Utilizing T-Lymphocyte Activation-Related Cytokines to Predict Non-Responsiveness to Treatment in Pediatric Kawasaki Disease

Abstract

Objective: To investigate the predictive value of T-lymphocyte activation-related cytokines in non-responsive Kawasaki disease.

Methods: Eighty-two children with Kawasaki disease, hospitalized from June 2022 to December 2023, were divided into two groups based on treatment response: the sensitive Kawasaki disease group (n=71) and the non-responsive Kawasaki disease group (n=11). Serum levels of T-lymph activation-related cytokines, including interleukin-2, 6, 7, 12, 15, 17, and tumor necrosis factor alpha, were measured before and after IVIG treatment in both groups. The differences in cytokine levels between the two groups were compared pre- and post-treatment. The ability of these cytokines to discriminate non-responsive Kawasaki disease was evaluated using ROC curves to determine the cut-off value.

Results: Before initial treatment, IL-2, IL-6, IL-7, IL-12, IL-15, IL-17, and tumor necrosis factor-α values were significantly higher in the non-responsive Kawasaki disease group compared to the sensitive Kawasaki disease group. Comparisons before and after initial treatment showed significant decreases in IL-6 and 17 in the sensitive Kawasaki disease group and significant decreases in IL-6 and 7 in the non-responsive Kawasaki disease group. IL-6 and 17 significantly increased in the sensitive group compared to the non-responsive group after initial treatment. The ROC curves indicated that IL-6 predicted the area under the curve (AUC) for non-responsive Kawasaki disease to be 0.859 before treatment and 0.920 after treatment. Similarly, IL-17 had AUC values of 0.699 before treatment and 0.884 after treatment.

Conclusion: Reassessing IL-6 and IL-17 following the initial treatment for Kawasaki disease may improve early warning signals for unresponsive Kawasaki disease.

Keywords: Kawasaki disease; T-lymphocyte activation; cytokines; immunoglobulin; unresponsive Kawasaki disease.

Figure 1

The study assessed the variations in cytokine levels associated with T lymphocyte activation (IL-2, 6, 7, 12, 15, 17, and TNF-α) across different groups. (A) Significant differences in IL-2 levels were noted between the sensitive and non-responsive groups, both before and after treatment (P < 0.05). (B) Statistically significant differences in IL-6 levels were observed in the sensitive group compared to the non-reactive group before and after treatment, as well as within each group over the treatment period (P < 0.05). (C) Statistically significant differences were observed pre-treatment between the sensitive and non-responsive groups, and within the non-responsive group before and after treatment (P < 0.05). (D) There was a significant difference in IL-12 levels between the sensitive and non-responsive groups before treatment (P < 0.05). (E) Statistically significant differences were noted between the IL-15-sensitive and non-responsive groups before and after treatment (P < 0.05). (F) Significant variations in IL-17 levels were noted between the sensitive and non-responsive groups before and after treatment, including changes within the sensitive group itself (P < 0.05). (G) A significant difference in TNF-α levels was found between the sensitive and non-responsive groups before treatment (P < 0.05).

Figure 2

The ROC curves illustrate the pre- and post-treatment area under the curve for IL-6 and IL-17 in predicting nonresponsive Kawasaki disease.