Role of Pyroptosis in IVIG-Resistant Kawasaki Disease and the Establishment of a New Predictive Model

Shiyu Li, Yang Zhou, Yini Wen, Yali Wu, Fan Liu, Yan Ding Department of Pediatric Immunology, Wuhan Children’s Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, People’s Republic of ChinaCorrespondence: Yan Ding; Fan Liu, Department of Pediatric Immunology, Wuhan Children’s Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, People’s Republic of China, Email [email protected]; [email protected]: Intravenous immunoglobulin (IVIG) resistance may be an increased risk of coronary artery lesions which is the serious complication of Kawasaki disease (KD). Early and accurate identification of IVIG-resistant patients has an important clinical value.Objective: To establish a new predicting model by detecting the pyroptosis markers with other clinical indicators.Methods: A total of 144 children with KD who were hospitalized in Wuhan Children’s Hospital from January 2022 to December 2022 were enrolled in this prospective study, among whom 120 had IVIG-sensitive KD and 24 had IVIG-resistant KD. NLRP3, ASC, CASP1, and GSDMD were quantified in peripheral blood cells of all children by using Real-time Quantitative Polymerase Chain Reaction (QRT-PCR) assay. The enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of cytokines like IL-1β and IL-18. Logistic regression analysis was performed to identify independent risk factors for resistance to IVIG in children with KD. These meaningful variables were assigned values based on odds ratios and became components of the new risk assessment model. The prediction efficiency of this model was tested and evaluated based on the receiver operating characteristic (ROC) curves.Results: 1. IVIG-resistant KD group had significantly lower mRNA expression of CASP1 than IVIG-sensitive KD group (P< 0.05). 2. IVIG-resistant KD group had significantly higher level of serum procalcitonin (PCT) and tumor necrosis factor-α (TNF-α) and lower level of serum natrium (Na) than the IVIG-sensitive KD group (P< 0.05). 3. The assessment model had a sensitivity of 91.7% and a specificity of 69.2% in the prediction of IVIG-resistant KD (P< 0.001).Conclusion: Combined examination by CASP1 and above laboratory indexes has clinical practical value for the diagnosis of IVIG-resistant KD.Keywords: Kawasaki disease, resistance to intravenous immunoglobulin, CASP1, child