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NETosis is critical in patients with severe community-acquired pneumonia.

ABSTRACT: Pneumonia is the fourth leading cause of death globally, and the reason for the high mortality rate of patients with severe community-acquired pneumonia (SCAP) remains elusive. Corticosteroid treatment reduces mortality in adults with SCAP but can cause numerous adverse events. Therefore, novel therapeutic targets need to be explored and new adjunctive immune drugs are urgently required. We analyzed the transcriptome data of peripheral blood leukocytes from patients with SCAP and healthy controls from three perspectives: differentially expressed genes, predicted functions of differentially expressed long non-coding RNAs, and transcriptional read-through. We discovered that the NETosis pathway was top-ranked in patients with SCAP caused by diverse kinds of pathogens. This provides a potential therapeutic strategy for treating patients. Furthermore, we calculated the correlation between the expression of genes involved in NETosis and the ratio of arterial oxygen partial pressure to fractional inspired oxygen. We identified four novel potential therapeutic targets for NETosis in patients with SCAP, including H4C15, H3-5, DNASE1, and PRKCB. In addition, a higher occurrence of transcriptional read-through is associated with a worse outcome in patients with SCAP, which probably can explain the high mortality rate of patients with SCAP.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9709478 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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NETosis is critical in patients with severe community-acquired pneumonia.

Zhang Yiming Y Li Yan Y Sun Na N Tang Hanqi H Ye Jun J Liu Yang Y He Quan Q Fu Yangyang Y Zhu Huadong H Jiang Chengyu C Xu Jun J

Frontiers in immunology 20221115

Pneumonia is the fourth leading cause of death globally, and the reason for the high mortality rate of patients with severe community-acquired pneumonia (SCAP) remains elusive. Corticosteroid treatment reduces mortality in adults with SCAP but can cause numerous adverse events. Therefore, novel therapeutic targets need to be explored and new adjunctive immune drugs are urgently required. We analyzed the transcriptome data of peripheral blood leukocytes from patients with SCAP and healthy control ...[more]

PMID: 36466920

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Project description:IntroductionCommunity-acquired pneumonia (CAP) requiring intensive care unit (ICU) treatment commonly causes acute respiratory failure with high mortality. Kallistatin, an endogenous tissue kallikrein inhibitor, has been reported to be protective in various human diseases. The aim of this study was to assess the correlations of kallistatin with other biomarkers and to determine whether kallistatin levels have a prognostic value in severe CAP.MethodsPlasma samples and clinical data were prospectively collected from 54 patients with severe CAP requiring ICU admission. Seventeen healthy control subjects were included for comparison. Plasma kallistatin, kallikrein, and other biomarkers of inflammation (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, C-reactive protein (CRP)), and anti-coagulation (protein C, anti-thrombin III) were measured on days 1 and 4 of ICU admission. Comparison between survivors (n = 41) and nonsurvivors (n = 13) was performed.ResultsPlasma kallistatin was significantly consumed in severe CAP patients compared with healthy individuals. Lower day 1 kallistatin levels showed a strong trend toward increased mortality (P = 0.018) and higher day 1 CURB-65 scores (P = 0.004). Plasma kallistatin levels on day 1 of ICU admission were significantly decreased in patients who developed septic shock (P = 0.017) and who had acute respiratory distress syndrome (P = 0.044). In addition, kallistatin levels were positively correlated with anti-thrombin III and protein C and inversely correlated with IL-1β, IL-6, and CRP levels. In a multivariate logistic regression analysis, higher day 1 CURB-65 scores were independent predictors of mortality (odds ratio = 29.9; P = 0.009). Also, higher day 1 kallistatin levels were independently associated with a decreased risk of death (odds ratio, 0.1) with a nearly significant statistical difference (P = 0.056). Furthermore, we found that a cutoff level of 6.5 μg/ml of day 1 kallistatin determined by receiver operating characteristic curves could be used to distinguish between patients who survived in 60 days and those who did not.ConclusionsThese results suggest that kallistatin may serve as a novel marker for severe CAP prognosis and may be involved in the pathogenesis of CAP through antiinflammatory and anticoagulation effects.

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NETosis is critical in patients with severe community-acquired pneumonia.

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NETosis is critical in patients with severe community-acquired pneumonia.

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