Citrullinated histone H3 and procalcitonin in the diagnosis and predicting the outcome of septic shock

Sepsis and septic shock stimulate a massive inflammatory response during which neutrophil extracellular traps (NETs) release citrullinated histone H3 (CitH3) into the circulation, leading to tissue damage, coagulopathy, and organ failure. This study aimed to assess serum levels of CitH3 in patients with septic and non-septic shock in intensive care units and to study their correlation to septic shock severity. The study was conducted at Ain Shams University Hospitals and included 72 adult participants: 24 with septic shock, 24 with non-septic shock, and 24 healthy controls. Serum CitH3and procalcitonin (PCT) levels were measured using ELISA, and blood cultures were performed for septic shock patients. Median CitH3 levels were 5.58 ng/mL in healthy controls, 44.38 ng/mL in non-septic shock, and 198.7 ng/mL in septic shock patients (p < 0.001). CitH3 strongly correlated with SOFA scores (Non-septic: r = 0.793; Septic: r = 0.786) and ICU stay in septic patients (r = 0.477, p = 0.019). ROC analysis showed CitH3 performed better than PCT in distinguishing septic from non-septic shock patients (AUC 0.946 vs 0.747, p = 0.012) and from controls (AUC 0.991 vs 0.853, p = 0.017). Direct comparison also showed that CitH3 had superior predictive performance for mechanical ventilation (p = 0.038). CitH3 could be considered a reliable biomarker of septic shock. It can be regarded as a valuable tool for predicting prognosis and severity of sepsis. CitH3 could be a promising candidate for routine integration into sepsis management protocols.