Decoy Receptor 3 as a Biomarker for Diagnosis of Bacterial Sepsis

2020 ◽  
Vol 29 (3) ◽  
pp. 153-162
Author(s):  
Maha H Hassan ◽  
Manal M Yassin ◽  
Yahia M Hassan ◽  
Nagwa M Abo El Magd

Background: Sepsis is a leading cause of morbidity and mortality that has a global burden. Early recognition of sepsis and differentiating it from similar conditions is crucial. Objective: In the present study we aimed to measure the serum level of decoy receptor 3 (DcR3) in sepsis patients to study its role as a promising biomarker for bacterial sepsis. Methodology: The present study included 30 patients, divided into a sepsis group (n=15) and a systemic inflammatory response syndrome (SIRS) group (n=15), and 15 healthy controls. Sepsis patients were identified by positive blood culture or positive 16S ribosomal DNA (rDNA) polymerase chain reaction (PCR) results. SIRS patients were identified by negative blood culture or negative 16S rDNA PCR results. Serum DcR3 level was measured by quantitative enzyme-linked immunosorbent assay (ELISA). Receiver-operating characteristic (ROC) curve analysis was performed for DcR3 and C-reactive protein (CRP) alone and in combination. Results: The serum DcR3 level was significantly higher in sepsis than SIRS patients and healthy controls (5.21 ± 2.28 ng/mL, 1.96 ± 0.90 ng/mL, and 0.95 ± 0.79 ng/mL, respectively). The ROC area under the curve (AUC) of DcR3 for sepsis versus SIRS was 0.920 at a cut-off >2.4 ng/mL, with 93.33% sensitivity and 86.67% specificity. The AUC of combined positive DcR3 and positive CRP for sepsis versus SIRS was 0.967 with 93.33% sensitivity and 100% specificity. Conclusion: DcR3, alone or in combination with CRP, is a promising biomarker for distinguishing sepsis from SIRS patients and may efficiently guide physicians to identifying sepsis patients, for whom the further usage of new diagnostics can be cost-effective.

2020 ◽  
Author(s):  
Jian-ting Wen ◽  
Jian Liu ◽  
Hui Jiang ◽  
Lei Wan ◽  
Ling Xin ◽  
...  

Abstract Background: The most severe effects of rheumatoid arthritis (RA) are loss of physical function, which may have a significant impact on self-perception of patient (SPP). However, the inherent relationship between SPP and the key proteins is not clear. The aim of this study was to get an insight into SPP of RA in connection with the the apoptosis-related proteins. Methods: We set out to investigate changes of the apoptosis-related proteins expression in the peripheral blood mononuclear cells (PBMCs) of RA. Additionally, we aimed to correlate the apoptosis-related proteins expression profiles with SPP and clinical indexes. To this end, we employed antibody microarrays of the the apoptosis-related proteins in PBMCs from four RA patients and seven healthy controls. We used bioinformatics to screen several the apoptosis-related proteins. To validate key protein candidates, we performed Enzyme linked immunosorbent assay (ELISA) on 30 RA patients and 30 healthy controls. Results: We found the expression of ten the apoptosis-related proteins (caspase3, CD40, SMAC, HSP27, HTRA, IGFBP-1, IGFBP-6, sTNF-R1, sTNF-R2, TRAILR-3) were significantly altered in PBMCs of RA patients. Receiver operating characteristic (ROC) curve analysis suggested that these ten the apoptosis-related proteins are potential biomarkers of RA. Spearman Correlation analysis and Logistic-regression analysis revealed that the 10 selected the apoptosis-related proteins correlated with SPP and clinical indexes. Conclusion: Therefore, we highlight some the apoptosis-related proteins may serve as potential biomarkers in prediction of SPP for RA patients, although the underlying mechanisms need to be further explored.


2019 ◽  
Vol 9 (1-2) ◽  
pp. 15-23
Author(s):  
Katrina Thompson ◽  
Joseph Connor

Introduction: Decoy receptor 3 (DcR3) has shown utility as a reliable surrogate marker. Levels of DcR3 in the serum increase and remain elevated in several disease states including cancer and sepsis. In inflammatory conditions, DcR3 is upregulated in inflammatory cells to suppress exponential immune propagation. The use of DcR3 as an indication of sepsis has been documented in the antemortem setting, but its use in the postmortem setting is unknown. The purpose of this study is to evaluate postmortem DcR3 as a marker of antemortem sepsis. Methods: A retrospective investigation was performed to identify patients whose primary cause of death fell into one of four cohorts (control, cancer, culture-positive sepsis, and suspected culture-negative sepsis). Serum was obtained and tested by a commercially available enzyme-linked immunosorbent assay to quantify DcR3 levels. Results: Twenty-five of 47 samples contained detectable levels of DcR3 (average 0.75 ± 0.3 ng/mL). Comparing culture-positive sepsis to the control cohort at a cutoff value of 0.26 ng/mL, DcR3 positivity showed a sensitivity of 64% and a specificity of 73%. Compared to each other, patients with cancer had similar values to those with culture-positive sepsis (P = .90). Time of specimen collection had a negative role in detection and quantification (P = .038). Discussion: Several studies have shown DcR3 may be a viable antemortem biomarker of sepsis, but its use in postmortem sepsis testing has not been adequately investigated. This study shows that in postmortem testing, DcR3 shows less sensitivity and specificity with a relatively short window for proper testing.


2019 ◽  
Author(s):  
Jing Li ◽  
Min Ming ◽  
Yonghong Han

Abstract Background This study aimed to investigate the predictive value of JNK pathway-associated phosphatase (JKAP) level for severe acute pancreatitis (SAP) risk, and its association with disease severity, inflammation and in-hospital mortality in SAP patients. Methods Our study recruited 50 SAP patients, 50 moderate-severe acute pancreatitis (MSAP) patients, 50 mild acute pancreatitis (MAP) patients and 50 healthy controls. And the serum samples were obtained from all acute pancreatitis patients within 24 hours after admission and from health controls at their enrollment to detect JKAP level by enzyme-linked immunosorbent assay. Results JKAP level was decreased in SAP patients compared with healthy controls, MSAP and MAP patients. And receiver operating characteristics (ROC) curve analysis revealed that JKAP could not only distinguish SAP patients from healthy controls (AUC: 0.914, 95%CI: 0.857-0.971), but also differentiate SAP patients from MAP patients (AUC: 0.869, 95%CI: 0.802-0.937) and MSAP patients (AUC: 0.712, 95%CI: 0.610-0.813). In SAP patients, JKAP was negatively correlated with Ranson score, acute physiology and chronic health care evaluation II (APACEH II) score, sequential organ failure assessment (SOFA) score and C-reactive protein (CRP). And lower JKAP level, higher CRP level, Ranson score, APACEH II score and SOFA score were associated with increased in-hospital mortality in SAP patients. Additionally, ROC curve analysis showed that JKAP could predict decreased in-hospital mortality in SAP patients (AUC: 0.720, 95%CI: 0.526-0.914). Conclusions JKAP might serve as a biomarker for disease risk and management for SAP.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chuchu Gao ◽  
Zongtai Feng ◽  
Lixia Wang ◽  
Xingxing Zhao ◽  
Kai Fu ◽  
...  

Abstract Background Late-onset sepsis (LOS) is a systemic inflammatory response syndrome in neonates, and the molecular mechanism of LOS is incompletely characterized. The purpose of this study was to explore the potential value of receptor interacting protein 3 (RIP3) in LOS. Methods 63 neonates with LOS supported by positive culture and 79 neonates without sepsis were enrolled in this study from September 2019 to March 2021. Plasma RIP3 was detected by enzyme-linked immunosorbent assay (ELISA) and assessed along with the whole blood hypersensitive C-reactive protein (hs-CRP) level and platelet count (PLT). Differences in RIP3, hs-CRP and PLT between the two groups were compared. Changes in the three indicators in sepsis were also observed after treatment. The diagnostic value of indicators for LOS was evaluated by receiver operating characteristic (ROC) curve analysis. Results In the sepsis group, RIP3 and hs-CRP levels were significantly higher than those in the control group (RIP3, p < 0.0001; hs-CRP, p < 0.0001), and PLT was significantly lower than that in the control group (p < 0.0001). After treatment, RIP3 and hs-CRP levels among septic survivors were significantly decreased (p < 0.0001) and PLT significantly improved (p = 0.0216). With RIP3 > 15,845.19 pg/mL, hs-CRP > 5.00 mg/L, and PLT < 204.00 × 109/L as the positive criteria, the sensitivity values of the three indicators in the diagnosis of LOS were 69.8%, 60.3%, 60.3%, respectively, and the specificity values were 92.4%, 96.2%, 79.8%, respectively. The combination of RIP3, hs-CRP and PLT had a sensitivity of 77.8% and specificity of 97.5%. Conclusions RIP3 may contribute to the early diagnosis of LOS and monitoring of treatment effect. The combined detection of RIP3, hs-CRP and PLT may be more effective than individual detection in the diagnosis of LOS.


2019 ◽  
Vol 47 (5) ◽  
pp. 510-515 ◽  
Author(s):  
Ali Ovayolu ◽  
Gamze Ovayolu ◽  
Erbil Karaman ◽  
Tuncay Yuce ◽  
Abdulkadir Turgut ◽  
...  

Abstract Objectives To evaluate the maternal serum endocan levels in pregnant women complicated by preterm premature rupture of membranes (PPROM) and to compare the results with healthy pregnancies. Methods This cohort study included 31 pregnant women with PPROM and 34 gestational age-matched healthy subjects in the third trimester of pregnancy. The blood for analysis was obtained on the day of diagnosis and serum endocan levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. The pregnant women were observed until the delivery and perinatal data were noted. Results No significant differences regarding maternal age, body mass index, gravidity, parity and gestational age at sampling were observed (P > 0.05). Mean serum endocan level was significantly higher in the PPROM group than in healthy controls (1490 ± 632 pg/mL vs. 972 ± 586 pg/mL, respectively; P: 0.001). Serum endocan concentration was positively correlated with C-reactive protein (CRP) (r = 0.754, P < 0.001) and white blood cells count (WBC) (r = 0.712, P:0.001). The receiver operating characteristic (ROC) curve analysis showed that endocan with a cut-off point of 1198 ng/dL indicated women with PPROM with sensitivity of 64.5% and specificity of 35.1% (area under curve 0.731, confidence interval 0.61–0.85). Conclusion Serum endocan level was significantly elevated in the PPROM patients than in healthy controls. The endocan level may be a useful indicator of endothelial dysfunction/inflammation in PPROM cases.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Su Lin ◽  
Bing Wu ◽  
Yehong Lin ◽  
Mingfang Wang ◽  
Yueyong Zhu ◽  
...  

Aims. To explore the expression level and clinical significance of decoy receptor 3 (DcR3) in patients with acute-on-chronic liver failure (ACLF).Methods. Serum DcR3 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 76 patients with ACLF and 41 non-ACLF patients with chronic liver disease. Blood routine and liver functions were accessed for their correlations with DcR3.Results. Serum DcR3 in ACLF patients was significantly higher than that in non-ACLF patients. It was positively correlated with neutrophilic granulocyte, aspartate aminotransferase, prothrombin time, and international standardized ratio, but negatively correlated with platelet and serum albumin. At the early stage, the level of DcR3 was not significantly different between the survival and nonsurvival group of ACLF. However, at the late stage, DcR3 increased in nonsurvival and gradually decreased in survivals. The baseline DcR3 could not sufficiently predict the outcome of ACLF, while the change of DcR3 within the first week displayed a better predictive value than model for end-stage liver disease (MELD) score.Conclusions. DcR3 was highly expressed in patients with ACLF and correlated with several clinical indices. Dynamic change of DcR3 might predict the prognosis of ACLF.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Peng Wang ◽  
Chun Li ◽  
Fan Zhang ◽  
Xuzhe Ma ◽  
Xiaodong Gai

Aim. B7-H4 is member of the B7 family that negatively regulates the immune response, which are associated with tumor development and prognosis. The present study is aimed at examining serum B7-H4 expression and exploring its contribution to diagnosis in patients with colorectal cancer. Methods. We determined serum expressions of B7-H4, carcinoembryonic antigen (CEA), osteopontin (OPN), and tissue polypeptide-specific antigen (TPS) in 59 patients with colorectal cancer and 29 healthy volunteers and analyzed the diagnostic value of B7-H4 combined with CEA, OPN, or TPS detection for colorectal cancer. B7-H4, OPN, and TPS serum expressions were measured by enzyme-linked immunosorbent assay, and CEA was measured by electrochemical luminescence detection. Results. Serum B7-H4 levels were significantly higher in colorectal cancer patients compared with paired normal controls (P=0.001). B7-H4 serum level was positively correlated with infiltration depth, tumor masses, and lymph node metastasis (P=0.004, P=0.016, and P=0.0052, respectively). We also detected serum expression of B7-H4 before and after radical resection and showed that B7-H4 levels decreased significantly during the first week postoperation (P=0.0064). We used receiver operating characteristic (ROC) curve analysis to indicate the potential diagnostic values of these markers. The areas under the ROC curves (AUC) for B7-H4, OPN, TPS, and CEA were 0.867, 0.805, 0.812, and 0.833, respectively. The optimal sensitivity and specificity of B7-H4 for discriminating between colon cancer patients and healthy controls were 88.2% and 86.7%, respectively, using a cut-off of value of 78.89 ng/mL. However, combined ROC analysis using B7-H4 and CEA revealed an AUC of 0.929, with a sensitivity of 98.9% and a specificity of 80.4% for discriminating colon cancer patients from healthy controls. Conclusions. B7-H4 was highly expressed in the serum in colorectal cancer patients. Detection of B7-H4 plus CEA showed significantly increased sensitivity and specificity for discriminating between colorectal cancer patients and healthy controls compared to individual detection of these markers. Combined detection of serum B7-H4 and CEA may thus have the potential to become a new laboratory method for the early clinical diagnosis and prognostic evaluation of colorectal cancer.


2021 ◽  
Author(s):  
Xuewei Cui ◽  
Yongyan Shi ◽  
Xinyi Zhao ◽  
Xindong Xue ◽  
Jianhua Fu

Abstract Background: This study assessed the clinical value of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) for early recognition of nosocomial infections in preterm infants.Methods: 120 neonates were finally analyzed, 89 with sepsis were compared with 31 noninfected controls. IL-6, CRP and PCT were measured at certain stages. Receiver-operating characteristic (ROC) curve analysis was used to determine the best cutoff values of IL-6, CRP, and PCT for diagnosing sepsis.Results: In the sepsis group, IL-6 peaked 6 hours after the infection onset and dropped to normal 24–48 hours after the infection was controlled. The best cutoff values of IL-6, CRP, and PCT were >99.6 pg/mL, >9.27 mg/L, and >2.33 ng/mL, respectively. The areas under the ROC curves were 0.888, 0.823, and 0.953, respectively. When PCT was combined with IL-6 or IL-6 and CRP, the sensitivity and specificity were >85%.Conclusion: IL-6, CRP, and PCT are reliable indicators for early diagnosis of nosocomial infections in preterm infants. Combining PCT and IL-6, CRP with IL-6 and PCT levels could improve the accuracy of clinical diagnosis.


2020 ◽  
Author(s):  
Xuewei Cui ◽  
Yongyan Shi ◽  
Xinyi Zhao ◽  
Xindong Xue ◽  
Jianhua Fu

Abstract Background: This study assessed the clinical value of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) for early recognition of nosocomial infections in preterm infants.Methods: 120 neonates were enrolled, 89 with sepsis were compared with 31 noninfected controls. IL-6, CRP and PCT were measured at certain stages of infection. Receiver-operating characteristic (ROC) curve analysis was used to determine the best cutoff values of IL-6, CRP, and PCT for diagnosing sepsis.Results: The levels of IL-6, CRP, and PCT in the sepsis group were significantly higher than those in the control group before antibiotic treatment. In the sepsis group, IL-6 peaked 6 hours after the infection onset and dropped to normal 24–48 hours after the infection was controlled. The best cutoff values of IL-6, CRP, and PCT were >99.6 pg/mL, >9.27 mg/L, and >2.33 ng/mL, respectively. The areas under the ROC curves were 0.888, 0.823, and 0.953, respectively.When PCT was combined with IL-6 or IL-6 and CRP, the sensitivity and specificity were >85%.Conclusion: IL-6, CRP, and PCT are reliable indicators for early diagnosis of nosocomial infections in preterm infants. Combining PCT and IL-6 CRP, IL-6, and PCT levels could improve the accuracy of clinical diagnosis.


Author(s):  
Jon Roger Eidet ◽  
Maja Akopian ◽  
Ole K. Olstad ◽  
Øystein Kalsnes Jørstad ◽  
Morten C. Moe ◽  
...  

Abstract Background To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls. Methods Thirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay. Results Relative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population. Conclusions The acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.


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