Decrease in Histidine-Rich Glycoprotein as a Novel Biomarker to Predict Sepsis Among Systemic Inflammatory Response Syndrome

Objectives: Many biomarkers for sepsis are used in clinical practice; however, few have become the standard. We measured plasma histidine-rich glycoprotein levels in patients with systemic inflammatory response syndrome. We compared histidine-rich glycoprotein, procalcitonin, and presepsin levels to assess their significance as biomarkers. Design: Single-center, prospective, observational cohort study. Setting: ICU at an university-affiliated hospital. Patients: Seventy-nine ICU patients (70 with systemic inflammatory response syndrome and 9 without systemic inflammatory response syndrome) and 16 healthy volunteers. Interventions: None. Measurements and Main Results: We collected blood samples from patients within 24 hours of ICU admission. Histidine-rich glycoprotein levels were determined using enzyme-linked immunosorbent assay. The median histidine-rich glycoprotein level in healthy volunteers ( n = 16) was 63.00 µg/mL (interquartile range, 51.53–66.21 µg/mL). Histidine-rich glycoprotein levels in systemic inflammatory response syndrome patients ( n = 70; 28.72 µg/mL [15.74–41.46 µg/mL]) were lower than those in nonsystemic inflammatory response syndrome patients ( n = 9; 38.64 µg/mL [30.26–51.81 µg/mL]; p = 0.049). Of 70 patients with systemic inflammatory response syndrome, 20 had sepsis. Histidine-rich glycoprotein levels were lower in septic patients than in noninfective systemic inflammatory response syndrome patients (8.71 µg/mL [6.72–15.74 µg/mL] vs 33.27 µg/mL [26.57–44.99 µg/mL]; p < 0.001) and were lower in nonsurvivors ( n = 8) than in survivors ( n = 62) of systemic inflammatory response syndrome (9.06 µg/mL [4.49–15.70 µg/mL] vs 31.78 µg/mL [18.57–42.11 µg/mL]; p < 0.001). Histidine-rich glycoprotein showed a high sensitivity and specificity for diagnosing sepsis. Receiver operating characteristic curve analysis for detecting sepsis within systemic inflammatory response syndrome patients showed that the area under the curve for histidine-rich glycoprotein, procalcitonin, and presepsin was 0.97, 0.82, and 0.77, respectively. In addition, survival analysis in systemic inflammatory response syndrome patients revealed that the Harrell C -index for histidine-rich glycoprotein, procalcitonin, and presepsin was 0.85, 0.65, and 0.87, respectively. Conclusions: Histidine-rich glycoprotein levels were low in patients with sepsis and were significantly related to mortality in systemic inflammatory response syndrome population. Furthermore, as a biomarker, histidine-rich glycoprotein may be superior to procalcitonin and presepsin.