Prokineticin 2 as a potential biomarker for the diagnosis of Kawasaki disease

Abstract

Kawasaki disease is a pressing acute self-limiting inflammatory disorder disease which lack of specific biomarkers. Our research aims to investigate the serum expression of a novel immune regulator PK2 in children with Kawasaki disease and to evaluate the ability of PK2 to predict Kawasaki disease. A total of 70 children with Kawasaki disease in the Children's Hospital of Chongqing Medical University who were first diagnosed, 20 children with common fever admitted to hospital due to bacterial infection during the same period, and 31 children underwent physical examination were included in this study. Venous blood was collected for complete blood count, CRP, ESR, PCT, and PK2 before clinical intervention. The predictive potential of PK2 as a biomarker for the diagnosis of Kawasaki disease was judged by correlation analysis, the receiver operating characteristic (ROC) and combined score. Compared with healthy children and children with common fever, children diagnosed with Kawasaki disease had significantly lower serum PK2 concentrations (median 28,503.7208 ng/ml, 26,242.5484 ng/ml, and 16,890.2452 ng/ml, respectively, Kruskal-Wallis test: p < 0.0001). Analysis of the existing indicators in other laboratories showed that WBC (Kruskal-Wallis test: p < 0.0001), PLT (Kruskal-Wallis test: p = 0.0018), CRP (Mann-Whitney U: p < 0.0001), ESR (Mann-Whitney U: p = 0.0092), NLR (Kruskal-Wallis test: p < 0.0001), and other indicators were significantly increased compared with healthy children and children with common fever, RBC (Kruskal-Wallis test: p < 0.0001), and Hg (Kruskal-Wallis test: p < 0.0001) were significantly decreased in children with Kawasaki disease conversely. In the analysis of the Spearman correlation, it was found that serum PK2 concentration and NLR ratio were significantly negatively correlated in children with Kawasaki disease (r_s = -0.2613, p = 0.0301). In the analysis of the ROC curves, it was found that the area under the PK2 curve was 0.782 (95% confidence interval 0.683-0.862; p < 0.0001), the ESR was 0.697 (95% confidence interval 0.582-0.796; p = 0.0120), the CRP was 0.601 (95% confidence interval 0.683-0.862; p = 0.1805), and the NLR was 0.735 (95% confidence interval 0.631-0.823; p = 0.0026). PK2 can significantly predict Kawasaki disease independently of CRP and ESR (p < 0.0001). The combined score of PK2 and ESR can significantly improve the diagnostic performance of PK2 (AUC = 0.827, 95% CI 0.724-0.903, p < 0.0001). The sensitivity was 87.50%, the sensitivity was 75.81%, the positive likelihood ratio was 6.0648, and the Youden index was 0.6331. PK2 has the potential to be a biomarker for early diagnosis of Kawasaki disease, and the combined use of ESR can further improve its diagnostic performance. Our study identifies PK2 as an important biomarker for Kawasaki disease and provides a potential new diagnostic strategy for Kawasaki disease.

Keywords: Diagnostic marker; Kawasaki disease; Prokineticin2.