Neo-epitope of Gasdermin D C-terminal fragment detection identifies pyroptosis in sepsis: an exploration study

Background Gasdermin D (GSDMD)-mediated pyroptosis, a critical component of the innate immune response, is triggered by pathogenic microbial infections and plays a key role in host defense mechanisms. This process involves the cleavage of GSDMD by inflammatory caspases, releasing carboxy-terminal fragments (GSDMD-CT). Monitoring GSDMD-CT levels represents a promising approach for inflammatory diseases, including sepsis and systemic inflammatory response syndrome (SIRS). Methods We developed an immunoassay to measure plasma GSDMD-CT concentrations in 109 healthy individuals, 137 patients with SIRS, and 100 patients with sepsis. The diagnostic utility of GSDMD-CT in distinguishing sepsis from SIRS or healthy controls was assessed using receiver operating characteristic (ROC) analysis, alongside correlations with procalcitonin (PCT), and C-reactive protein (CRP). Results Plasma GSDMD-CT levels were significantly elevated in patients with sepsis compared to healthy control and SIRS groups. ROC analysis demonstrated an area under the curve (AUC) of 0.8701, with a sensitivity of 91.00% and specificity of 60.55% for differentiating sepsis from HC. Comparable performance was observed in distinguishing SIRS from HC. Diagnostic accuracy was further enhanced when GSDMD-CT was combined with PCT. Strikingly, GSDMD-CT mirrored the kinetic profile of PCT in antibiotic-treated patients with bacterial infections. Conclusion The GSDMD-CT assay demonstrates high sensitivity as a biomarker, offering potential for early and differential diagnosis of sepsis across diverse pathogens.