Plasma sTREM-1 Levels Research Articles

Dynamic Changes in Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Sepsis with Respect to Antibiotic Susceptibility.

Proper antibiotic administration is crucial for sepsis management. Given the escalating incidence of antimicrobial resistance, there is a pressing need for indicators of antimicrobial susceptibility with short turnaround times. This study aimed to investigate the potential of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as an early biomarker for in vivo antibiotic susceptibility in patients with sepsis. We conducted a retrospective analysis of plasma samples from patients enrolled in a pre-established study designed to investigate prognostic biomarkers in patients with sepsis or septic shock. Baseline and 6 h sTREM-1 levels were examined using enzyme-linked immunosorbent assays. The primary outcome of the study was the comparison of percentage changes in sTREM-1 levels at the 6 h relative to baseline with respect to antibiotic susceptibility. Of the 596 patients enrolled in the pre-established study, 29 with a median age of 75.8 and a 28-day mortality rate of 17.2% were included in the present analysis. Among these patients, 24 were classified into the susceptible group, whereas the remaining five were classified into the resistant group. The trend in plasma sTREM-1 levels differed with respect to antibiotic susceptibility. Moreover, percentage change in sTREM-1 levels at the 6 h relative to baseline was significantly higher in the resistant group (P = 0.028). The trend in plasma sTREM-1 levels in patients with sepsis differed with respect to antibiotic susceptibility, with a higher percentage change in patients treated with inappropriate antibiotics. These findings indicate the potential utility of sTREM-1 as an early biomarker of antibiotic susceptibility.

The associations between plasma soluble Trem1 and neurological diseases: a Mendelian randomization study

BackgroundTriggering receptor expressed on myeloid cell 1 (Trem1) is an important regulator of cellular inflammatory responses. Neuroinflammation is a common thread across various neurological diseases. Soluble Trem1 (sTrem1) in plasma is associated with the development of central nervous system disorders. However, the extent of any causative effects of plasma sTrem1 on the risk of these disorders is still unclear.MethodGenetic variants for plasma sTrem1 levels were selected as instrumental variables. Summary-level statistics of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), epilepsy, cerebrovascular diseases, and migraine were collected from genome-wide association studies (GWASs). Whether plasma sTrem1 was causally associated with neurological disorders was assessed using a two-sample Mendelian randomization (MR) analysis, with false discovery rate (FDR)-adjusted methods applied.ResultsWe inferred suggestive association of higher plasma sTrem1 with the risk of AD (odds ratio [OR] per one standard deviation [SD] increase = 1.064, 95% CI 1.012–1.119, P = 0.014, PFDR = 0.056). Moreover, there was significant association between plasma sTrem1 level and the risk of epilepsy (OR per one SD increase = 1.044, 95% CI 1.016–1.072, P = 0.002, PFDR = 0.032), with a modest statistical power of 41%. Null associations were found for plasma sTrem1 with other neurological diseases and their subtypes.ConclusionsTaken together, this study indicates suggestive association between plasma sTrem1 and AD. Moreover, higher plasma sTrem1 was associated with the increased risk of epilepsy. The findings support the hypothesis that sTrem1 may be a vital element on the causal pathway to AD and epilepsy.

Urine soluble triggering receptor expressed on myeloid cells-1 is a novel biomarker for active lupus nephritis: a case-control study.

To determine the value of plasma and urine sTREM-1 levels as a biomarker of lupus nephritis (LN) as well as extra-renal systemic lupus erythematosus (SLE). Consecutive adult patients with SLE attending a tertiary lupus clinic in 2016-2018 were prospectively divided into 3 groups according to SLEDAI-2K and renal-SLEDAI scores: active renal lupus (ARL), active non-renal lupus (ANL), and inactive lupus (IL). Blood and spot urine samples from each group and matched healthy subjects were analysed by means of ELISA for plasma and urine sTREM-1 levels. The cohort included 59 patients (mean age 41.5+2.9 years, 85% female) with SLE: 15 ARL, 14 ANL, and 30 IL. The ARL group had higher scores on the SLEDAI-2K and renal-SLEDAI, and higher urine protein/creatinine ratio than the other patient groups (p=0.0001 for all). Plasma sTREM-1 level was highest in the ANL group (p=0.0085). Urine sTREM-1 level was higher in the whole SLE cohort than the healthy controls (p=0.0249), and higher in the ARL group than the others (p=0.0044). Neither plasma nor urine sTREM-1 level was associated with non-renal SLE features. On Spearman correlation analysis, urine sTREM-1 level, but not plasma sTREM-1 level, was correlated positively with renal-SLEDAI score (r=0.34, p=0.018), inversely with serum C3 and C4 levels (r=-0.42, p=0.0027 and r=-0.28, p=0.056, respectively), and positively with proteinuria (UPCR: r=0.32, p=0.0305). Urine sTREM-1 might serve as a potential biomarker of active renal SLE.

Plasma Concentrations of sTREM-1 as Markers for Systemic Adverse Reactions in Subjects Treated With Weekly Rifapentine and Isoniazid for Latent Tuberculosis Infection.

BackgroundA regimen of once-weekly rifapentine plus isoniazid for 3 months (3HP) is an effective treatment for subjects with latent tuberculosis infection; however, no reliable biomarker exists for predicting systemic adverse reactions (SARs) to 3HP treatment.MethodsThis prospective, multi-center study evaluated the plasma concentrations of soluble triggering receptors expressed on myeloid cells (sTREM)-1 and sTREM-2 in subjects undergoing 3HP treatment and examined the associations between these biomarkers and SARs.ResultsThis study enrolled 80 consecutive subjects receiving 3HP treatment, 25 of whom had SARs and 55 of whom did not. Subjects with SARs presented higher concentrations of sTREM-1 at baseline than those without SARs (240.1 ± 19.1 vs. 176.7 ± 9.4 pg/mL, P = 0.001). The area under the receiver operating characteristic curves revealed that day 1 plasma levels of sTREM-1 (0.708, 95% CI, 0.584–0.833, P = 0.003) and sTREM-2 (0.343, 95% CI, 0.227–0.459, P = 0.025) as well as the sTREM-1/sTREM-2 ratio (0.748, 95% CI, 0.638–0.858, P = 0.001) had modest discriminative power pertaining to the development of SARs. An sTREM-1 level exceeding the cut-off value (>187.4 pg/mL) (hazard ratio [HR], 6.15; 95% CI 1.67–22.70, P = 0.006) and a sTREM-2 below the cut-off value (<237.2 pg/mL) (HR, 4.46; 95% CI 1.41–14.1, P = 0.011) were independent predictors of SARs after controlling for other variables.ConclusionsPlasma sTREM-1 and sTREM-2 levels are useful biomarkers for predicting SARs during 3HP treatment.Clinical trial governmentNCT04655794

STREM-1 Predicts Disease Severity and Mortality in COVID-19 Patients: Involvement of Peripheral Blood Leukocytes and MMP-8 Activity.

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.

Elevated Plasma Soluble Triggering Receptor Expressed on Myeloid Cells-1 Level in Patients with Acute Coronary Syndrome (ACS): A Biomarker of Disease Severity and Outcome

Background and Aims Plasma levels of soluble triggering receptor expressed on myeloid cells (sTREM-1) reflect innate immune cell activation. We sought to evaluate sTREM-1 levels in patients with acute coronary syndrome (ACS) and their predictive value for disease severity and outcome. Methods Plasma sTREM-1 levels were prospectively measured by ELISA in 121 consecutive patients with new-onset (≤24 h) chest pain at arrival to the emergency department (ED) and 73 healthy controls. Secondary endpoints were the association of plasma levels of sTREM-1 with day 30 and month 6 major adverse cardiovascular events (MACE) defined as death, ACS, stroke, and need for coronary revascularization, as well as with CAD severity. The primary endpoint of the study was the association of plasma sTREM-1 level at the time of admission to the ED with a diagnosis of ACS at day 30. Results Fifty-nine patients (48.7%) were diagnosed with ACS and 62 (51.3%) with nonspecific chest pain (NSCP). Median plasma sTREM-1 level at admission was significantly higher in the ACS group than the NSCP group and the control group (539.4 ± 330.3 pg/ml vs. 432.5 ± 196.4 pg/ml vs. 230.1 ± 85.5 pg/ml, respectively; P < 0.001) and positively correlated with the number of stenosed/occluded coronary arteries on angiography (P < 0.001). On logistic regression analysis, higher sTREM-1 levels predicted definite ACS vs. NSCP determined on day 30 (OR 1.29, 95% CI 1.07-1.54, P = 0.01) as well as with recurrent ACS (P = 0.04) and stroke (P = 0.02) at 6 months. Conclusions Plasma sTREM-1 levels are significantly elevated in patients with ACS and might serve as a biomarker differentiating ACS from NSCP in the ED as well as an inflammatory biomarker for coronary artery disease severity and outcome.

Diagnostic Value of Plasma Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Children with Urinary Tract Infections

Abstract Objective The aim of the present study was to evaluate the diagnostic value of soluble triggering receptor on myeloid cells-1 as a novel marker for diagnosis of childhood urinary tract infections (UTI). Methods This study enrolled 30 pediatric patients diagnosed with acute febrile UTIs; 30 healthy children were included as the control group. The blood samples from the patients and healthy controls were collected for a soluble triggering receptor on myeloid cells-1 (sTREM-1) test. Results The study group was composed of 9 males and 21 females, and the mean age of the study population was 6.6 ± 3.2 (range = 1–14) years. sTREM-1 levels were significantly higher in UTI patients than in the controls (592 ± 323 vs. 490 ± 299 pg/mL, p = 0.04). The receiver operating curve analysis revealed a cut-off value of soluble triggering receptor expressed on myeloid cells-1 of 514 ng/mL (area under the curve = 0.562). When the cut-off value was taken 514 pg/mL, soluble triggering receptor expressed on myeloid cells-1 had a sensitivity of 57% and a specificity of 50% for the diagnosis of UTI. Conclusion The present study revealed that plasma sTREM-1 level may be elevated in UTI and may therefore serve as a useful predictive tool for the diagnosis of UTI.

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in neonatal sepsis

Background Efficient and accurate diagnosis of neonatal sepsis is challenging. The potential impact for a reduction in morbidity and mortality as well as antibiotic usage has stimulated the ongoing search for biomarkers of early sepsis. The objective of this pilot study was to quantify the levels of sTREM-1 and correlate with blood cultures and inflammatory markers in neonates evaluated for sepsis. Methods Neonates with suspected sepsis were enrolled (n = 83; Preterm n = 35; Term n = 48). Routine bloods for sepsis evaluation were included and plasma sTREM-1 levels were quantified by ELISA. Results Term and preterm neonates (n = 83; Preterm n = 35; Term n = 48) were enrolled and 16 neonates had positive blood cultures (preterm n = 15; term n = 1). sTREM-1 levels were not significantly different in infants with culture-positive or culture-negative sepsis (356 ± 218 pg/mL and 385 ± 254 pg/mL respectively). The immature-to-total granulocyte (I/T) ratio showed a significant positive correlation with sTREM-1 in the preterm group with positive blood cultures. Additionally, sTREM-1 showed a positive correlation with CRP in the preterm group with negative blood cultures. Conclusions sTREM-1 was associated with traditional markers of inflammation (I/T ratio and CRP). However, in this cohort sTREM-1 did not improve the early detection of neonatal culture-positive sepsis.

Utility of sTREM-1 and Presepsin (sCD14-ST) as Diagnostic and Prognostic Markers of Sepsis.

Sepsis is a condition prevalent among hospitalized patients which carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, and then effective treatment can be initiated rapidly. Traditionally, diagnosis was based on the presence of two or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exists, and clinicians still rely on a number of traditional and novel biomarkers to discriminate between patients with and without infection, as the cause of deterioration. The present study aims to observe the changes of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and presepsin (sCD14-ST) 1evels in plasma of sepsis patients and explore the diagnosis and prognosis of sepsis. Sixty patients with sepsis admitted to the Department of Critical Care medicine in Hainan General Hospital from October 2013 to March 2019 were selected as the experimental group. Also chosen in the same period were 60 cases of hospitalized non-sepsis patients as a control group. Plasma levels of sTREM-1 and presepsin were determined by enzyme-linked immunosorbent assay (ELISA) in the 60 patients with sepsis and the 60 non-sepsis patients. Changes of sTREM-1 and presepsin plasma 1evels were observed in the survival subgroup and non-survival subgroup of the patients with sepsis on days 1, 4, 7, and the day of discharge or death. Plasma levels of sTREM-1 and presepsin in the patients with sepsis were higher than those in the control group on the day of admission (p < 0.01). The levels of sTREM-1 and presepsin in the septic shock group were significantly higher than those in the sepsis group (p < 0.01). Plasma levels of sTREM-1 and presepsin showed a decreasing trend in the survival subgroup of the patients with sepsis, while maintaining high 1evels or increased in the subgroup of non-survivors. At different time points, the plasma levels of sTREM-1 and presepsin of the subgroup of non-survivors were all significantly higher than the subgroup of survivors. There was a significant positive correlation between plasma 1evels of sTREM-1 and presepsin (r = 0.596, p < 0.01). According to the plasma sTREM-1, presepsin, CRP, and PCT levels on the first day of enrollment in patients with sepsis, ROC curve analysis was performed and AUC was calculated. The results showed that the AUC values of sTREM-1 and presepsin were relatively high, which was 0.925 and 0.910, respectively. The AUC of PCT and CRP were slightly lower, which was 0.861 and 0.816, respectively (p < 0.01). ROC curve was used to study the value of sTREM-1 and presepsin in the diagnosis of sepsis, which suggested that sTREM-1 and presepsin should be significantly superior to CRP and PCT levels. The sTREM-1 combined with presepsin had the highest AUC. sTREM-1 has been shown to have an optimal threshold of 125.00 pg/mL for the diagnosis of sepsis, the specificity was 86.0% and the sensitivity was 87.0%. Presepsin has been shown to have an optimal threshold of 1,025.00 pg/mL for the diagnosis of sepsis, the specificity was 83.0% and the sensitivity was 85.0%. The sTREM-1 and presepsin plasma levels have great reference value for the diagnosis of sepsis, and the sTREM-1 and presepsin plasma levels are relative to the severity of sepsis. It is helpful to evaluate treatment effect and prognosis of sepsis by dynamically monitoring the plasma 1evels of sTREM-1 and presepsin.

Elevated plasma level of soluble triggering receptor expressed on myeloid cells-1 is associated with inflammation activity and is a potential biomarker of thrombosis in primary antiphospholipid syndrome

BackgroundSoluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is an innate-immune receptor found in blood. Its presence reflects innate immune cell activation. We sought to investigate plasma sTREM-1 levels in patients with primary antiphospholipid syndrome (PAPS).MethodsA cross-sectional, case-control design was used. Plasma sTREM-1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA) in consecutive patients diagnosed with PAPS or asymptomatic antiphospholipid antibody (APLA) carriers and controls.ResultsThe study cohort included 33 patients with PAPS, 10 asymptomatic APLA carriers, and 73 controls. Mean plasma sTREM-1 levels were significantly higher in patients with PAPS (299.2 ± 146.7 pg/ml) and thrombotic PAPS-ever (current and past thrombotic event) (327.2 ± 151.3 pg/ml) compared with controls (230.2 ± 85.5 pg/ml; p = 0.006 and p = 0.003, respectively), patients with thrombotic PAPS compared with patients with past obstetric APS (195.12 ± 58.52 pg/ml, p = 0.01) and APLA carriers (215.8 ± 51.6 pg/ml, p = 0.02), patients with current thrombotic PAPS (429.5 ± 227.5 pg/ml) compared with patients with past thrombotic PAPS (289.5 ± 94.65 pg/ml, p = 0.01), and patients with PAPS who had ever had a stroke or venous thromboembolic event compared with patients who had not (p = 0.007 and p = 0.02, respectively). On receiver operator characteristic curve analysis, plasma sTREM-1 levels differentiated patients with current thrombotic PAPS from asymptomatic APLA carriers and controls, with an area under the curve of 0.7292 (p = 0.0014) and 0.88 (p < 0.0001), respectively. Multivariate regression analysis to identify sTREM-1 predictors (thrombotic PAPS-ever, age, and sex) yielded an independent association of sTREM-1 levels with thrombotic PAPS (p < 0.0001).ConclusionsPlasma sTREM-1 levels are significantly elevated in patients with thrombotic PAPS. Levels of sTREM-1 might serve as a biomarker for thrombosis in patients with PAPS.

Study of plasma levels of soluble triggering receptor expressed on myeloid cells-1 in rheumatoid arthritis and its correlation with disease activity and tumor necrosis factor-\u03b1

Aim of the workThe triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell surface receptor expressed mainly on monocytes and neutrophils. It acts as an amplifier of inflammatory response in acute and chronic inflammatory states. The aim of this work was to study the plasma-soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in rheumatoid arthritis (RA) patients and its correlation with disease activity and tumor necrosis factor-α (TNF-α).Patients and methodsThis study included 80 patients with RA and 20 age-matched and sex-matched controls. All were subjected to demographic, clinical, laboratory, and radiological studies using the 28-joint Disease Activity Score, erythrocyte sedimentation rate, complete blood count, and radiograph of both hands. Plasma levels of sTREM-1 and TNF-α were measured with enzyme-linked immunosorbent assay.ResultsRA patients had significantly higher sTREM-1 and TNF-a levels compared with controls (206.32±125.75 and 17.83±11.88; P<0.001) and (190.82±69.46 and 54.75±9.46; P<0.001). In RA patients, sTREM-1 levels were found to be positively correlated with 28-joint Disease Activity Score, erythrocyte sedimentation rate, and TNF-a level (r=0.408, P=0.001; r=0.287, P=0.010; r=0.749, P=0.001). sTREM-1 level was significantly increasing as patients had increasing disease activity (F-test=20.62; P=0.001).ConclusionRA patients had higher sTREM-1 and TNF-a level compared with controls, and sTREM-1 level was correlated with disease activity, suggesting that sTREM-1 plays a role in the inflammatory process associated with TNF-a, and it may be a useful disease activity marker in RA. TREM-1 may be a safe therapeutic strategy for RA, as blocking TREM-1 signaling was found to suppress inflammatory responses without affecting the immune system to fight bacterial infection.

Soluble triggering receptor expressed on myeloid cells-1 as a marker for early detection of infection in postoperative patients

Background Triggering receptor expressed on myeloid cells-1 (TREM-1) is recently identified to be involved in infectious inflammatory responses, and is expressed on the surface of immune cells. TREM-1 acts in synergy with toll-like receptor signaling pathways in amplifying the inflammatory response mediated by several microbial components. TREM-1 is not upregulated with noninfectious inflammatory disorders. Besides its membranous form, a soluble counterpart of TREM-1 (sTREM-1) exists that is released with several infectious processes. Objective Our study aimed to investigate the diagnostic and prognostic value of plasma sTREM-1 levels in postoperative patients with sepsis. Patients and methods Samples were collected from 50 postoperative patients presented with systemic inflammatory response syndrome (SIRS) and a suspected infection to estimate plasma sTREM-1 level within the first 12 h, day 3, and day 7 postoperatively, together with C-reactive protein and lactate. Patients were classified according to absence or presence of infection into SIRS and sepsis groups; the sepsis group was further subdivided according to absence or presence of organ dysfunction into sepsis and septic shock subgroups. Results With high significant difference, sTERM-1 was capable of distinguishing SIRS from sepsis, and also between sepsis and septic shock subgroups, with sensitivity, specificity, and predictive values comparable with other candidate indicators on day 1, day 3, and day 7 (P The best cutoff value of sTREM-1 for differentiating SIRS from sepsis was 95 pg/ml, which yielded a sensitivity of 97.2%, specificity 92.8%, positive predictive value 97.2%, negative predictive value 92.9%, and area under the curve of 0.983, whereas the best cutoff value of sTREM-1 for prediction of death in postoperative patients with sepsis was 400 pg/ml, which yielded a sensitivity of 97.6%, specificity 87.5%, positive predictive value 97.6%, negative predictive value 87.5%, and area under the curve AUC of 0.955,. Conclusion We conclude that sTREM-1 could act as an early detector of infection in postoperative patients and also as a predictor for mortality by an accuracy superior to other sepsis parameters.

Soluble TREM-1 as a diagnostic and prognostic biomarker in patients with septic shock: an observational clinical study

Objectives: The impact of TREM-1-mediated inflammation was investigated in different inflammatory settings.Methods: Secondary analyses of an observational clinical pilot study, including 60 patients with septic shock, 30 postoperative controls and 30 healthy volunteers.Results: Plasma levels of sTREM-1 were found to identify patients with septic shock more effectively than procalcitonin and C-reactive protein. Moreover, sTREM-1 was identified to be an early predictor for survival in patients with septic shock.Conclusion: Due to its diagnostic as well as prognostic value in sepsis syndrome, implementation of sTREM-1 measurements in routine diagnostics should be taken into account.

Diagnostic value of soluble triggering receptor expressed on myeloid cells in paediatric sepsis: a systematic review.

BackgroundDifferential diagnosis between sepsis and non-infectious inflammatory disorders demands improved biomarkers. Soluble Triggering Receptor Expression on Myeloid cells (sTREM-1) is an activating receptor whose role has been studied throughout the last decade. We performed a systematic review to evaluate the accuracy of plasma sTREM-1 levels in the diagnosis of sepsis in children with Systemic Inflammatory Response Syndrome (SIRS).MethodsA literature search of PubMed, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and ISI Web of Knowledge databases was performed using specific search terms. Studies were included if they assessed the diagnostic accuracy of plasma sTREM-1 for sepsis in paediatric patients with SIRS. Data on sensitivity, specificity, positive predictive value, negative predictive value, area under receiver operating characteristic curve were extracted. The methodological quality of each study was assessed using a checklist based on the Quality Assessment Tool for Diagnostic Accuracy Studies.ResultsNine studies comprising 961 patients were included, four of which were in newborns, three in children and two in children with febrile neutropenia. Some data from single studies support a role of sTREM-1 as a diagnostic tool in pediatric sepsis, but cannot be considered conclusive, because a quantitative synthesis was not possible, due to heterogeneity in studies design.ConclusionsThis systematic review suggests that available data are insufficient to support a role for sTREM in the diagnosis and follow-up of paediatric sepsis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13052-016-0242-y) contains supplementary material, which is available to authorized users.

The effects of paeoniflorin injection on soluble triggering receptor expressed on myeloid-1 (sTREM-1) levels in severe septic rats.

Paeoniflorin (PAE) is the most abundant compound in Xuebijing injection widely used to treat sepsis. We aimed to investigate effect of PAE on expression of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in a rat model of sepsis. Wistar rats were divided into Normal, Model, and PAE groups (n=20 each). Endotoxin was administrated at 5 mg/ml/kg in Model and PAE rats to establish rat sepsis model. 1 h after endotoxin administration, PAE was administrated at 4 ml/kg in PAE group once per day for 3 days. Routine blood tests and biochemical indexes were assessed, including aspartate aminotransferase (AST) and creatine kinase-MB (CK-MB). The plasma sTREM-1 level was measured using quantitative ELISA. At the end of experiment, the small intestine, liver, kidney and lung were subjected to pathological examinations. A rat model of sepsis-induced multiple organ dysfunction syndrome (MODS) was established successfully with endotoxin administration (5 mg/ml/kg), evidenced by histo-pathological examinations, routine blood tests and biochemical indexes: platelet count decreased and white blood cell count increased (p<0.05), CK-MB and AST increased (p<0.05). PAE treatment significantly reduced the plasma levels of AST, CK-MB, and sTREM-1, compared to Model group (p<0.05). Meanwhile, sepsis-induced damages in the liver, lung, stomach and intestinal mucosa were also markedly ameliorated by PAE treatment. PAE demonstrated a significantly protective effect in a rat model of sepsis by decreasing plasma sTREM-1 level, reducing inflammation, preventing MODS and protecting organ functions.

Differential Expression Of TREM-1 In Myelogenous Leukemia Cells

ObjectivesTriggering receptor expressed on myeloid cells (TREM) -1 is a receptor as a member of the immunoglobulin superfamily expressed on the cell-surface of neutrophils, monocytes and macrophages. This receptor amplifies the inflammatory response, activating the signaling pathway. TREM-1 expression is associated with mature myeloid cell development. TREM-1 is shed from the membrane of activated macrophages without the transmembrane and intracellular domains, and can be found as soluble TREM (sTREM)-1. Soluble TREM-1 is thought to negatively regulate TREM receptor signaling. Some studies currently reported that TREM-1 regulates the malignant behavior of cancer cells in lung cancer and HCC. However, no related studies about the role of TREM-1 in leukemia have been carried out. The aims of this study was investigated the TREM-1 expression in myelogenous leukemia cells. MethodsThirty-five patients with AML, twenty-five patients with CML and a control group of eleven healthy people were subjected to the study. TREM-1 expressions on the surfaces of leukemia cells were measured by flow cytometry. Plasma sTREM-1 levels were measured by ELISA. ResultsIn this study, our results provide the first evidence that TREM-1 was differentially expressed in myelogenous leukemia cells. The TREM-1 mean ratio of median fluorescence intensity (mean ratio of MFI) was 3.13±0.88 and 2.52±0.40 in CML and AML patients, respectively. The TREM-1 mean ratio of MFI was 3.03±1.40 in myelogenous leukemia cell lines (K562, HL60, THP-1). The TREM-1 mean ratio of MFI was 5.37±0.88 in healthy controls. Compared to healthy controls, myelogenous leukemia cells had decreased TREM-1 expressions (P<0.001). The TREM-1 mean ratio of MFI was 4.89±0.60 in patients who are in complete remission after Novartis's Gleevec therapy. Compared with CML patient groups, patients who are in complete remission after Gleevec therapy had rising TREM-1 expressions (P<0.01). TREM-1 expressions of patients who are in complete remission after Gleevec therapy were slightly lower than the healthy controls, but this did not reach significance. No significant difference in TREM-1 expressions was seen between AML and CML patient groups, male and female patient groups, and cells derived from peripheral blood and bone marrow of the same leukemia patients (p>0.1).In addition, the plasma sTREM-1 levels were measured by ELISA. sTREM-1 levels was 48.54±57.63pg/mL for AML group and 43.72±23.93pg/mL for CML group. Results indicated that plasma sTREM-1 levels significantly higher in AML and CML patients than that in healthy controls (P<0.01). However, there was no significant difference in plasma sTREM-1 levels observed in AML patient group compared with CML patient group, male patients group compared with female patients group, and plasma from peripheral blood compared with plasma from bone marrow of the same leukemia patients (p>0.1).An ongoing project focuses on the relationship between the function of TREM-1 and occurrence, progression and prognosis of myelogenous leukemia, advances will be reported in time. ConclusionTREM-1 expression on leukemia cells was significantly lower in patients with AML and CML than those in healthy controls and patients in complete remission had increased TREM-1 expression. Patients with AML and CML had increased plasma soluble TREM-1. The TREM-1 expression on leukemia cells had an inverse correlation with plasma sTREM-1 level in AML and CML patients. Disclosures:No relevant conflicts of interest to declare.

AB0165 Plasma soluble triggering receptor expressed on myeloid cells-1 (strem-1) levels are correlated with disease activity in rheumatoid arthritis

BackgroundTriggering receptor expressed on myeloid cells 1 (TREM-1) is an immunoglobulin-like cell surface receptor mainly expressed on neurtophils, monocytes and macrophages. TREM-1 serves as a critical amplifier of inflammatory signaling,...

Diagnostic Value of Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Critically-Ill, Postoperative Patients With Suspected Sepsis

IntroductionThe lack of specific clinical manifestations for sepsis frequently leads to delayed diagnosis. Identification of sensitive and specific indicators that can be easily assessed, accurately reflect infection severity and prognosis and are clinically important in the differential diagnosis of sepsis, is of great significance. The purpose of this study was to evaluate the diagnostic and prognostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in high selected, mostly postoperative patients with suspicion of sepsis. MethodsFifty-two consecutive patients hospitalized in a surgical intensive care unit with suspicion of infection included 14 patients with systemic inflammatory response syndrome (SIRS), 9 patients with sepsis, 14 patients with severe sepsis and 15 patients with septic shock. Within 12 hours after enrollment, plasma levels of sTREM-1, procalcitonin (PCT), tumor necrosis factor (TNF)-α, interleukin-6 and C-reactive protein were measured and compared between subgroups to elucidate their diagnostic and prognostic values. ResultsPlasma sTREM-1 levels were higher in patients with sepsis than in patients with SIRS (111.7 versus 64.1 pg/mL, P<0.05), with sensitivity, specificity and a predictive value higher than those of PCT and TNF-α. Plasma sTREM-1 levels were significantly different between the sepsis, severe sepsis and septic shock subgroups (P<0.001). For the receiver operating characteristic for predicting death, the area under the curve of sTREM-1 was 0.861, similar to that of TNF-α, blood lactate and PCT (0.848, 0.719 and 0.706, respectively). ConclusionsIn postoperative patients, plasma levels of sTREM-1 and TNF-α could differentiate sepsis from SIRS. sTREM levels also reflected the severity of sepsis and were noninferior for prognosis compared with other biochemical indexes.

Differential pattern of cell-surface and soluble TREM-1 between sepsis and SIRS

ObjectiveTriggering receptor expressed on myeloid cells-1 (TREM-1) was reported to play a key roll in amplification of production of inflammatory cytokines. TREM-1 is suggested to be a specific biomarker for sepsis for this reason, but the clinical significance of TREM-1 has not been elucidated. We investigated TREM-1 expression on the cell-surface, and plasma levels of soluble TREM-1 (sTREM-1) in patients with non-infectious systemic inflammatory response syndrome (SIRS) and sepsis admitted to the ICU. MethodsThirty-five patients with SIRS and 21 patients with sepsis admitted to ICU were subjected to the study. TREM-1 expressions on the surfaces of monocytes and neutrophils were measured by flow cytometry. Plasma sTREM-1 level and serum interleukin (IL)-6 level were measured. ResultsSeptic patients had decreased TREM-1 expression, clearly on neutrophils or to a lesser extent on monocyte compared to SIRS patients on ICU admission (neutrophils p<0.001, monocyte p<0.05). TREM-1 expression on neutrophils had a significant inverse correlation with serum IL-6 level (r=−0.64, p<0.0001). Plasma sTREM-1 level in septic patients was significantly higher than that in SIRS patients (p<0.05). Plasma sTREM-1 level positively correlated with severity score and non-survivors had increased plasma sTREM-1 level compared to survivors in all SIRS/sepsis patients (p<0.05). ConclusionsPatients with sepsis had increased soluble TREM-1 and decreased TREM-1 expression on neutrophil compared to SIRS patients. sTREM-1 may be useful to evaluate disease severity and outcome of patients with SIRS or sepsis.

Measurement of Plasma STREM-1 in Patients With Severe Sepsis Receiving Early Goal-Directed Therapy and Evaluation of Its Usefulness

The plasma level of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) has been shown to be helpful in identifying critically ill patients with infection. However, it remains unknown whether it can be used to predict prognosis in patients with severe sepsis. This study investigated whether various inflammatory mediators, including sTREM-1, could be used as reliable markers to predict the prognosis of patients receiving early goal-directed therapy (EGDT). We prospectively enrolled patients 18 years or older with severe sepsis from April 2009 to May 2010 at a 2,000-bed university hospital. Patients were eligible if the initial resuscitation according to EGDT protocol was immediately performed at the emergency department. Plasma sTREM-1, C-reactive protein, and procalcitonin concentrations were measured on days 0, 3, 7, and 14. Soluble TREM-1 concentrations were significantly higher at admission and pre-EGDT in nonsurvivors (n = 16) than in survivors (n = 47) (514.1 pg/mL [interquartile range, 412.7-1,749.5 pg/mL] vs. 182.4 pg/mL [interquartile range, 54.3-327.0 pg/mL]; P = 0.001). Procalcitonin and C-reactive protein levels did not significantly differ, whereas central venous oxygen saturation and lactate levels at admission were significantly different between the two groups. The only sTREM-1 level remained significantly higher in nonsurvivors until death. On multivariate regression analysis, log(sTREM-1) (P = 0.028), central venous oxygen saturation (P = 0.022), and Simplified Acute Physiology Score II (P = 0.048) values at admission were independently significant. These results suggest that plasma sTREM-1 level at admission could be used as a marker to identify patients with a poor prognosis despite complete initial resuscitation in severe sepsis.