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GPR18 expression on PMNs as biomarker for outcome in patient with sepsis
Lanqiu Zhang1, Chongyang Qiu2, Lei Yang1
1Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, 300100, China.
Aims:
GPR18, a G protein-coupled receptor (GPCR), is involved in bacterial clearance and survival in microbial sepsis. In this study, we examine GPR18 expression on polymorphonuclear neutrophils (PMNs) of patients with sepsis and to determine the potential association with disease severity and outcomes.
Main Methods:
We enrolled 81 patients admitted at the intensive care unit (ICU) with the diagnosis of sepsis. PMNs GPR18 expression was measured by flow cytometry at admission. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHEII) as well as other biomarker were measured at admission. Cox regression analysis was used to determine the influence of PMNs GPR18 expression on 28-day mortality.
Key Findings:
Patients with sepsis had a decreased percentage of PMNs bearing GPR18 in comparison with healthy subjects (P < 0.001). Compared with survivors, non-survivors had lower percentage of GPR18-positive PMNs, but higher SOFA, APACHEIIscores, and WBC count. There were inverse correlations between the percentage of GPR18-positive PMNs and APACHEII, SOFA score and C-recreative protein (CRP). Using Kaplan-Meier analysis, high percentage of PMNs expressing GPR18 (≥43.7%) was associated with a preferable 28-day survival (P = 0.004). High percentage of PMNs expressing GPR18 (≥43.7%) was significantly and independently associated with 28-day mortality, with a hazard ratio of 0.36 (P = 0.37). Moreover, LPS-Toll-like receptor (TLR)4 signaling mediated the GPR18 expression on PMNs.
Significance:
These results indicate that decreased percentage GPR18-positive PMNs is associated with increased severity and poorer outcome of sepsis.
Insights
Decreased GPR18 expression on neutrophils in sepsis patients correlates with increased disease severity and mortality. Higher GPR18 levels on polymorphonuclear neutrophils (PMNs) indicate better survival outcomes in sepsis.
Area of Science:
- Immunology
- Critical Care Medicine
Background:
- G protein-coupled receptor 18 (GPR18) plays a role in bacterial clearance and survival during microbial sepsis.
- Polymorphonuclear neutrophils (PMNs) are crucial in the innate immune response to sepsis.
Purpose of the Study:
- To investigate GPR18 expression on PMNs in sepsis patients.
- To determine the association between GPR18 expression on PMNs and sepsis severity and patient outcomes.
Main Methods:
- 81 intensive care unit (ICU) patients diagnosed with sepsis were enrolled.
- PMN GPR18 expression was quantified using flow cytometry upon admission.
- Disease severity was assessed using Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHEII) scores, alongside other biomarkers.
Main Results:
- Sepsis patients exhibited reduced GPR18 expression on PMNs compared to healthy individuals.
- Non-survivors had lower GPR18-positive PMN percentages and higher SOFA/APACHEII scores than survivors.
- Elevated GPR18 expression on PMNs correlated inversely with disease severity markers (APACHEII, SOFA, CRP) and was linked to improved 28-day survival.
Conclusions:
- Reduced GPR18 expression on PMNs is associated with increased sepsis severity.
- GPR18 expression on PMNs may serve as a prognostic biomarker for sepsis outcomes.
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