Key result
Combined NLRP3 inflammasome profiling predicts pediatric viral myocarditis with an AUC of ~0.95.
Why the study?
The diagnostic significance of combined gene and protein expression analysis of NLRP3 inflammasome-mediated pyroptosis in pediatric viral myocarditis remained unclear.
Does combined gene and protein expression profiling of NLRP3 inflammasome-related markers improve diagnostic prediction of viral myocarditis in children compared to single indicators?
Case-Control (n=100)
No
Does combined gene and protein expression profiling of NLRP3 inflammasome-related markers improve diagnostic prediction of viral myocarditis in children compared to single indicators?
Effect estimate: AUC 0.954 (95% CI 0.914-0.994)
p-value: p=0.001
Combined assessment of NLRP3 inflammasome-related gene and protein expression levels provides a reliable approach for early diagnosis of pediatric viral myocarditis.
May aid early diagnosis of pediatric viral myocarditis via combined inflammasome markers; hypothesis-generating and requires prospective validation.
Purpose: Viral myocarditis (VMC) is a leading cause of heart failure and dilated cardiomyopathy in children. Pyroptosis, an inflammatory form of programmed cell death mediated by NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasomes, has been implicated in myocardial injury. However, the diagnostic significance of combined gene and protein expression analysis remains unclear. This study aimed to clarify the role of NLRP3 inflammasome-mediated pyroptosis in pediatric VMC and assess whether integrated gene-protein profiling could enhance diagnostic prediction. Patients and Methods: A total of 100 children were enrolled, including a case group (n=50, children with viral myocarditis hospitalized between September 2023 and September 2024) and a control group (n=50, patients with dilated cardiomyopathy during the same time period). The expression levels of proteins interleukin-1β (IL-1β), NLRP3, Gasdermin D (GSDMD) and Caspase-1, and genes GSDMD, NLRP3, and Caspase-1 in myocardial tissues were measured through enzyme-linked immunosorbent assay, immunohistochemistry, real-time polymerase chain reaction, and Western blotting. Results: No significant differences were found between the two groups regarding age, gender, or clinical history (P>0.05). Compared with the control group, the case group exhibited significantly higher expression of NLRP3, Caspase-1, GSDMD, and IL-1β at both protein and gene levels (P<0.05). Correlation analyses confirmed that these markers were positively associated with the presence of VMC. (P<0.05). Receiver operating characteristic (ROC) analysis revealed that the combined detection of gene and protein expression achieved a higher area under the curve (AUC) than any single indicator, demonstrating superior diagnostic accuracy. Conclusion: NLRP3 inflammasome-mediated pyroptosis plays a crucial role in the pathogenesis of viral myocarditis in children. The combined assessment of gene and protein expression levels provides a novel and more reliable approach for early diagnosis and risk evaluation of pediatric VMC, highlighting the potential of inflammasome-related biomarkers as therapeutic targets.
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Huang et al. (2025) conducted a case-control in Viral myocarditis (n=100). Combined gene and protein expression of NLRP3, Caspase-1, GSDMD, and IL-1β vs. Dilated cardiomyopathy controls was evaluated on Diagnostic prediction of viral myocarditis (AUC 0.954, 95% CI 0.914-0.994, p=0.001). The combined assessment of gene and protein expression of NLRP3, Caspase-1, GSDMD, and IL-1β achieved an AUC of 0.954 for predicting pediatric viral myocarditis, showing high diagnostic accuracy.
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