NINJ1: A NOVEL SEPSIS SEVERITY AND MORTALITY BIOMARKER

ABSTRACT: Background : Multiple cell death modalities are implicated in sepsis pathobiology. However, the clinical relevance of NINJ1, a key mediator of plasma membrane rupture during lytic cell death, in sepsis progression and outcomes has remained poorly explored. Methods: Circulating NINJ1 levels were measured in 116 septic intensive care unit (ICU) patients, 16 nonseptic ICU controls, and 16 healthy controls. Comparative analysis of serum NINJ1 across these groups was performed. Correlations between NINJ1 and clinical disease severity scores (Sequential Organ Failure Assessment [SOFA], Acute Physiology and Chronic Health Evaluation [APACHE II]) as well as laboratory parameters were examined in the sepsis cohort. Furthermore, we assessed the prognostic performance of NINJ1 for predicting 28-day mortality in septic patients using receiver operating characteristic (ROC) analyses. Results: Circulating NINJ1 levels were elevated in septic patients and positively correlated with sepsis severity scores. NINJ1 also showed positive correlations with liver injury markers (aspartate transaminase/alanine aminotransferase) and coagulation parameters (D-dimer, activated partial thromboplastin time, prothrombin time, thrombin time) in sepsis. Further analysis using the International Society on Thrombosis and Hemostasis overt disseminated intravascular coagulation scoring system revealed an association between NINJ1 and sepsis-induced coagulopathy. ROC analysis demonstrated that NINJ1 outperformed traditional inflammatory biomarkers procalcitonin and C-reactive protein in predicting 28-day sepsis mortality, although its prognostic accuracy was lower than SOFA and APACHE II scores. Combining NINJ1 with SOFA improved mortality prediction from an area under the curve of 0.6843 to 0.773. Conclusions: Circulating NINJ1 serves as a novel sepsis biomarker indicative of disease severity, coagulopathy and mortality risk, and its integration with SOFA and APACHE II scores substantially enhances prognostic risk stratification. These findings highlight the prospective clinical utility of NINJ1 for sepsis prognostication and monitoring, warranting further validation studies to facilitate implementation.