P2X7-Driven NLRP3 Inflammasome Activation Unveils Novel Serum Biomarkers Associated with the Severity of Mycoplasma pneumoniae Pneumonia in Children
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Background
Mycoplasma pneumoniae pneumonia (MPP), often referred to as walking pneumonia, is a common cause of community-acquired pneumonia (CAP) in children and presents with a broad clinical spectrum. While many cases are mild and self-limiting, a subset progresses to severe disease marked by hyperinflammation and systemic complications. This clinical variability presents challenges in early diagnosis and risk stratification. This study aimed to identify prognostic markers associated with MPP severity and explore potential underlying inflammatory mechanisms.
Methods
A total of 170 pediatric patients (1–14 years) were enrolled, including 120 MPP cases and 50 non-MPP controls. Serum levels of P2X7, NLRP3, IL-1β, and IL-18 were measured by ELISA. Routine laboratory markers (CRP, LDH, D-dimer, and IgE) were evaluated for their association with severe MPP (sMPP). Pathway enrichment and STRING network analyses were performed to contextualize the clinical markers within inflammation-related molecular pathways. ROC curve analysis was used to assess the predictive value of individual biomarkers.
Results
Multivariate logistic regression identified CRP, LDH, D-dimer, and IgE as independent risk factors for sMPP ( p <0.05). Pathway enrichment revealed these markers to be involved in acute-phase response, coagulation, cytokine signaling, and immune regulation. STRING network analysis further demonstrated their convergence on the NLRP3 inflammasome axis. Serum levels of P2X7, NLRP3, IL-1β, and IL-18 were significantly elevated in sMPP cases compared to non-severe MPP and controls ( p <0.001). ROC analysis showed all four had strong predictive performance (AUC > 0.7, p <0.001).
Conclusion
This study confirms that elevated levels of CRP, LDH, D-dimer, and IgE are independently associated with severe Mycoplasma pneumoniae pneumonia (sMPP), reflecting systemic inflammation, tissue injury, and immune dysregulation. Importantly, the concurrent upregulation of P2X7, NLRP3, IL-1β, and IL-18 in serum, supported by pathway enrichment and STRING network analyses, highlights a central role for inflammasome activation in sMPP pathogenesis. ROC curve analysis further demonstrated the strong predictive value of these inflammasome-related proteins. Collectively, these findings suggest that P2X7, NLRP3, IL-1β, and IL-18, in combination with conventional markers such as CRP, LDH, D-dimer, and IgE, may serve as valuable biomarkers for the early identification and risk stratification of children at risk for severe MPP, thereby enhancing diagnostic precision and informing clinical decision-making.
