Next generation exosome-based therapy can protect against systemic inflammation and sepsis-induced death.

The related innate immune system activation and diagnostic factors of sepsis are not fully understood. This study aimed to analyse the clinical value of full-length tryptophanyl-tRNA synthetase (WRS) induced through inflammatory stimuli in the detection of sepsis and mortality prediction in critically ill patients. In this retrospective analysis, we prospectively collected blood samples from patients in the medical intensive care unit (ICU) at Yonsei University College of Medicine, from March 2015 to June 2018. Sepsis detection and mortality prediction of WRS were compared to that with procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6), and with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. We enrolled 241 study patients, of whom 190 (78.8%) had been diagnosed with sepsis on ICU admission. The AUROCs for sepsis discrimination with WRS, PCT, CRP, and IL-6 levels, and SOFA and APACHE II scores were 0.864, 0.727, 0.625, 0.651, 0.840, and 0.754, respectively. The prediction of 28-day mortality in patients with sepsis using WRS levels was possible and non-inferior to that with the SOFA score. WRS secreted early in sepsis may be useful not only for early detection of sepsis but also for mortality prediction in critically ill patients.

Lee SH, et al. Immune Netw. 2022 Apr;22(2):e18. https://doi.org/10.4110/in.2022.22.e18

Background/Objectives: Sepsis is basically an inflammatory disease that involves the host’s immune response. Granzyme B, a cytotoxic protease, has garnered attention for its involvement in modulating immune responses. This study aimed to elucidate the clinical implications of granzyme B in critically ill patients with sepsis, focusing on plasma granzyme B levels as a potential prognostic marker. Methods: We conducted a retrospective analysis of sequentially collected blood samples from 57 sepsis patients admitted to the medical intensive care unit at Severance Hospital, a tertiary hospital in Seoul, South Korea. Clinical and laboratory data were comparatively analyzed between 28-day survivors and nonsurvivors. Results: The number of patients in the survivor and nonsurvivor groups was 32 (56.1%) and 25 (43.9%), respectively. Compared to survivors, nonsurvivors had higher APACHE II (23.5 vs. 34, p = 0.007) and SOFA (10 vs. 15, p = 0.001) scores, as well as increased levels of serum lactate (1.8 vs. 9.2 mmol/L, p < 0.001) and plasma granzyme B (28.2 vs. 71 pg/mL, p < 0.001). Granzyme B exhibited a robust area under the receiving operating characteristic (AUROC) for predicting 28-day mortality (AUROC = 0.794), comparable to lactate (0.804), SOFA (0.764), and APACHE II (0.709). The combined index of lactate and granzyme B demonstrated the highest AUROC (0.838) among all investigated predictors. Significant positive correlations were observed between log granzyme B and various inflammatory cytokines, including log IFN-γ (r = 0.780), IL-4 (r = 0.540), IL-10 (r = 0.534), and IL-6 (r = 0.520). Conclusions: Plasma granzyme B demonstrated fair short-term mortality prediction among patients admitted to the ICU, suggesting its potential utility for risk stratification and managing patients with sepsis.