Serum Soluble Receptor Research Articles

Clinical and Immunological Predictors of Hemorrhagic Fever with Renal Syndrome Outcome during the Early Phase.

The ability to accurately predict the early progression of hemorrhagic fever with renal syndrome (HFRS) is crucial for reducing morbidity and mortality rates in severely affected patients. However, the utility of biomarkers for predicting clinical outcomes remains elusive in HFRS. The aims of the current study were to analyze the serum levels of immune function-related proteins and identify novel biomarkers that may help ascertain clinical outcomes of HFRS. Enzyme-linked immunosorbent assay, Luminex, and bioanalyzer assays were used to quantitatively detect 15 biomarkers in 49 serum samples of 26 patients with HFRS. High hemoglobin (HGB) and low urine output (UO) levels were identified as potential biomarkers associated with the acute HFRS. The serum soluble urokinase plasminogen activator receptor (suPAR) and C-X-C motif chemokine ligand 10 (CXCL10) values increased in the early phase of diseases. Elevated suPAR, interleukin-10 (IL-10), CXCL10, and decreased transforming growth factor-beta 3 (TGF-β3) were representative predictors of the disease severity. Upregulation of the HGB showed a significant correlation with high levels of suPAR and CXCL10. Reduced UO positively correlated with increased suPAR, CXCL10, and TGF-β2, and decreased vascular endothelial growth factor and TGF-β3. The changing HGB and UO criteria, high suPAR, IL-10, CXCL10, and low TGF-β3 of HFRS raise significant awareness for physicians regarding prospective biomarkers for monitoring early warning signs of HFRS. This study provides critical insights into the clinical and immunological biomarkers for disease severity and progression in patients with HFRS to identify early predictions of fatal outcomes.

SERUM CARBOXYMETHYL-LYSINE AND SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS IN HYPERTHYROID AND HYPOTHYROID PATIENTS.

The formation and accumulation of advanced glycation end products (AGEs) are enhanced with increased oxidative stress and inflammatory conditions. A hyperthyroid and hypothyroid state is associated with oxidative stress. This study aimed to evaluate skin AGE deposition, serum carboxymethyl-lysine (CML), and serum soluble receptor for AGEs (sRAGE) levels in hypothyroid and hyperthyroid patients. A total of 203 subjects were included in this cross-sectional study. After excluding diabetes mellitus, 103 newly diagnosed hypothyroid patients, 50 newly diagnosed hyperthyroid patients, and 50 control (euthyroid) subjects were enrolled. All tests were done before beginning the appropriate treatment. Accumulated AGEs in the skin collagen were measured by skin autofluorescence (SAF) using an AGE Reader. SAF measurements were 1.82 ± 0.04, 1.80 ± 0.40, and 1.63 ± 0.30 arbitrary units for the hypothyroid, hyperthyroid, and euthyroid groups, respectively (p = 0.04). Serum CML levels were 8.2 ± 2.8, 10.2 ± 2.0, and 8.0 ± 3.3 ng/mL for the hypothyroid, hyperthyroid, and euthyroid groups, respectively (p = 0.01). sRAGE levels were similar between the groups. Serum thyroid-stimulating hormone and SAF measurements were positively correlated (r = 0.25, p = 0.02) in the hypothyroid group and negatively correlated in the hyperthyroid group (r = -0.36, p = 0.04). There was no correlation between CML and sRAGE levels. SAF measurements are increased in both hypo- and hyperthyroid normoglycemic patients. Serum CML levels are increased in hyperthyroid patients. Hypo and hyperthyroid states might be associated with acceleration of AGE accumulation and may have a long term effect on metabolic memory.

Relationship between familial mediterranean fever and soluble receptor for advanced glycation end products

Familial Mediterranean fever (FMF) is the most common hereditary autoinflammatory disease worldwide and is characterized by recurrent fever and serositis. Serum soluble receptor for advanced glycation end products (sRAGE) is an isoform of RAGE and sRAGE acts as a trap receptor for ligands and blocks the RAGE–ligand axis. This study aimed to examine the change in sRAGE levels in FMF and to investigate its relationship with inflammation. This study included patients with FMF (n=20) and healthy controls (n=22). Morbidity status, sRAGE levels, demographic and laboratory data were recorded. Pregnant women, individuals aged <18 years, and those with other chronic inflammatory diseases were excluded. Statistical Package for Social Sciences (SPSS) Version 22.0 was used to conduct all statistical analyses and all data are expressed as mean and standard deviation (SD). The serum sRAGE levels were 12.21±6.70 ng/mL and 4.44±2.89 ng/mL in the patient and control groups, respectively. Accordingly, the sRAGE levels of patients with FMF were significantly higher (p<0.001). Comorbidities had no effect on the sRAGE levels of the patient group and no correlation was found between the sRAGE and inflammatory biomarkers. sRAGE levels are elevated in FMF but does not seem to be a promising candidate as a biomarker for FMF.

DIAGNOSTIC ACCURACY OF SERUM FERRITIN AND SOLUBLE SERUM TRANSFERRIN RECEPTOR, TAKING BONE MARROW IRON STAIN AS A GOLD STANDARD FOR IRON DEFICIENCY ANEMIA IN HETEROGENOUS GROUP OF PATIENTS

Objective: To determine the diagnostic accuracy of serum ferritin and soluble serum transferrin receptor (sTfR), taking bone marrow iron stain as a gold standard for iron deficiency anaemia in heterogeneous group of patients.
 Study Design: Cross-sectional diagnostic accuracy study.
 Place and Duration of Study: Department of Diagnostic, Combined Military Hospital Lahore, from Mar to Aug 2020.
 Methodology: A total of 55 adult patients, of both genders, undergoing bone marrow examination for any reason were enrolled. Patients with known hemolytic condition (sickle cell anemia, megaloblastic anemia), taking erythropoietin/iron supplements, transfused red cell concentrate (RCC) recently or undergoing chemotherapy were excluded. Age, gender, clinical history and results of bone marrow examination, complete blood count (CBC), serum Ferritin and C-reactive protein (CRP) were recorded.
 Results: Serum ferritin was found to be less sensitive (28%) but more specific (100%) for reflecting reduced bone marrow iron stores as compared to sTfR (sensitivity: 60%, specificity: 96.6%). sTfR had highest likelihood ratio (15) and diagnostic accuracy (80%). On Receiver Operator Characteristic (ROC) graph Transferrin index (AUC=0.908) showed maximum accuracy, followed by Ferritin (AUC=0.884) and sTfR (AUC=0.879).
 Conclusion: Serum soluble transferring receptor (sTfR) and transferrin index has advantage over serum ferritin alone in predicting the bone marrow iron stores and differentiating iron deficiency anemia from anemia of chronic disease.

Serum soluble urokinase plasminogen activator receptor as a potential biomarker of renal impairment severity in diabetic nephropathy

AimsTo investigate serum soluble form of urokinase-type plasminogen activator receptor (suPAR) in patients with diabetic kidney disease (DKD) and biopsy-proven diabetic nephropathy (DN), its correlation with histological parameters and its capacity as a biomarker for renal impairment severity. MethodsWe conducted a cross-sectional study on 75 patients with diabetes mellitus (DM) and DKD, among whom 28 had biopsy-proven DN. ResultsAmong the 75 patients, 9 (12%) had type 1 and 66 (88%) type 2 DM. The median value of the serum suPAR level was 2857.2 pg/mL (1916.4–3700) in the entire cohort and 2472.1 pg/mL (1782.6–3745.8) in the biopsy-proven DN subgroup, respectively. suPAR was significantly correlated with diabetes duration, diabetic retinopathy, anti-proteinuric treatment, albuminuria, kidney function, DN class, interstitial fibrosis and tubular atrophy (IFTA) score and with interstitial inflammation score. suPAR had a good accuracy for the association with chronic kidney disease (CKD) stages G3b-5, macroalbuminuria, DN class IV, IFTA score 3 and interstitial inflammation score 2. ConclusionsSerum suPAR was increased in DN patients and was associated with DM duration, diabetic retinopathy, renoprotective treatment, kidney function, proteinuria, DN class, IFTA and interstitial inflammation scores. Also, suPAR had a good capacity as a biomarker for advanced renal impairment and severe histological lesions of DN.

Serum soluble (pro)renin receptor level as a prognostic factor in patients undergoing maintenance hemodialysis

The (pro)renin receptor [(P)RR)] is a multifunctional protein that is cleaved to generate the soluble (P)RR [s(P)RR], reflecting the status of the tissue renin-angiotensin system and/or activity of the (P)RR. The serum s(P)RR level is associated with arteriosclerosis, independent of other risk factors, in patients undergoing hemodialysis (HD). This study was conducted to investigate whether the s(P)RR level was associated with new-onset cardiovascular events or malignant diseases and poor prognosis in patients undergoing HD. Overall, 258 patients [70 (61–76) years, 146 males] undergoing maintenance HD were prospectively followed up for 60 months. We investigated the relationships between s(P)RR levels and new-onset cardiovascular events/ malignant diseases and mortality during the follow-up period using Cox proportional hazard analyses. The cumulative incidence of new-onset cardiovascular events (P = 0.009) and deaths (P < 0.001), but not of malignant diseases, was significantly greater in patients with higher serum s(P)RR level (≥ 29.8 ng/ml) than in those with lower s(P)RR level (< 29.8 ng/ml). A high serum s(P)RR level was independently correlated with cardiovascular mortality (95% CI 1.001–1.083, P = 0.046). The serum s(P)RR level was associated with cardiovascular events and mortality, thus qualifying as a biomarker for identifying patients requiring intensive care.

THE RELATIONSHIP BETWEEN sTREM-1 AND ACTIVATION OF INFLAMMATORY BOWEL DISEASES

Objective: In inflammatory bowel disease (IBD), there is no reliable biomarker, yet. We aimed to determine whether Serum Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) could be useful as a marker for the diagnosis and/or the determination of disease activity in patients with IBD. Material and Method: A total of 47 patients with ulcerative colitis (UC) and 25 patients with Crohn’s disease (CD) were prospectively enrolled. Clinical disease activity was analyzed using the Crohn’s Disease Activity Index (CDAI) for CD and the Truelove-Witts index for UC. Results: sTREM-1 levels were significantly lower in patients with IBD compared to healthy controls (p=0.001). In comparison of the levels of sTREM-1 between the different groups (CD, UC, and healthy controls) the difference was statistically significant. No considerable differences in sTREM-1 levels were determined in patients with active versus quiescent disease. The sTREM-1 levels negatively correlated with C-reactive protein, blood neutrophil-lymphocyte ratio, and positively with haemoglobin levels. Conclusion: sTREM-1 levels are decreased in IBD patients compared with the healthy individuals. It may, therefore, be useful for the diagnosis of IBD. However, it does not seem to be a precise marker of disease activity in IBD and cannot be suggested for assessing disease activity in these patients.

Correlation between serum carnitine level and Soluble Receptors for Advance Glycation End Products(sRAGE) in Clomiphene Citrate Resistant- PCOS Women

The most frequently diagnosed condition in women at the age of reproduction is the polycystic ovarian syndrome (PCOS).it could be related to a complex endocrine condition, due to its heterogeneity and uncertainty about its etiology, as the clinical highlights of PCOS incorporate those related to reproductive signs such as decreased frequency of ovulation, irregular menstrual cycles, decreased fertility. Carnitine plays a substantial role in weight loss, glucose tolerance, insulin function and fatty acid metabolism. Thus carnitine plays a crucial role in controlling obesity, insulin resistance, oxidative stress that are associated with PCOS .While, AGEs are a diverse group of reactive molecules that are formed endogenously by non-enzymatic reactions of carbonyl group of carbohydrates with free amino groups of proteins, nucleic acids or lipids. The soluble form of receptors of AGE (sRAGE) could play an important role in management obesity, insulin resistance, hyperandrogenism, oxidative stress which could be related to PCOS. This study was aimed to investigate serum levels of carnitine &amp; soluble receptors for advanced glycation end products (sRAGE) in clomiphene resistant PCOS .Besides assessing the correlation between serum levels of carnitine ,as well as, soluble receptors of AGE with hormonal ( LH, FSH&amp; Testosterone) and metabolic ( serum glucose , serum insulin &amp; HOMA-IR) markers in these patients .&#x0D; The study included thirty women with clomiphene resistant PCOS and thirty apparently healthy women, as a control .In order to measure serum total carnitine and serum soluble receptor of advance glycation end product (sRAGE in PCOS and control groups.&#x0D; The results of our study have shown a decreased serum levels of total carnitine in PCOS group in comparison with control group (48.05 and 59.73 nmol/ml, respectively), but there was no significant elevation in serum levels of sRAGE in patients group as compared with control group .In addition to a significant correlation between serum total carnitine and serum sRAGE levels (r=0.45, P-value=0.03). &#x0D; In conclusion serum total carnitine level was low in Clomiphene resistant-PCOS patients in comparison with control group. Although, sRAGE levels in clomiphene resistant- PCOS patients were not significantly different from the age and BMI-matching controls, but a significant correlation between serum total carnitine and sRAGE was detected.&#x0D; Key words: Poly cystic ovarian syndrome, soluble receptor of advance glycation end products (sRAGE) , SerumTotal Carnitine

Serum Soluble (Pro)renin Receptor Level as a Prognostic Factor in Patients Undergoing Maintenance Hemodialysis

Background: The (pro)renin receptor [(P)RR)] is a multifunctional protein with roles in angiotensin II-dependent and -independent intracellular cell signaling and as an adaptor protein between the Wnt receptor complex and vacuolar proton-translocating adenosine triphosphatase. The (P)RR is cleaved to generate soluble (P)RR [s(P)RR], reflecting the status of the tissue renin-angiotensin system and/or activity of the (P)RR. Patients undergoing hemodialysis (HD) have poor prognosis because of the increased prevalence of cardiovascular and malignant diseases. This study was conducted to investigate whether the s(P)RR level is associated with new onset of cardiovascular events or malignant diseases and prognosis in patients undergoing HD. Methods: A total of 258 patients undergoing maintenance HD who were enrolled in our cohort study investigating the relationships between serum s(P)RR levels and background factors were prospectively followed up for 60 months. We investigated the relationships between s(P)RR levels and new onset of cardiovascular events or malignant diseases and mortality during the follow-up period. Results: The cumulative incidence of new onset of cardiovascular events (P = 0.009) and cardiovascular deaths (P < 0.001), but not of malignant diseases, was significantly greater in patients with higher serum s(P)RR level (≥ 29.8 ng/ml) than in those with lower s(P)RR level (< 29.8 ng/ml). A high serum s(P)RR level was independently correlated with cardiovascular mortality (P = 0.046). Conclusions: These data showed that the serum s(P)RR level is associated with cardiovascular events and mortality, suggesting that the serum s(P)RR level could be used as a biomarker for selecting patients requiring intensive care.

Myeloid‐Cell–Specific IL‐6 Signaling Promotes MicroRNA‐223‐Enriched Exosome Production to Attenuate NAFLD‐Associated Fibrosis

NAFLD is associated with elevation of many cytokines, particularly IL-6; however, the role of IL-6 in NAFLD remains obscure. The aim of this study was to examine how myeloid-specific IL-6 signaling affects NAFLD by the regulation of antifibrotic microRNA-223 (miR-223) in myeloid cells. Patients with NAFLD or NASH and healthy controls were recruited, and serum IL-6 and soluble IL-6 receptor α (sIL-6Rα) were measured. Compared to controls, serum IL-6 and sIL-6Rα levels were elevated in NAFLD/NASH patients. IL-6 levels correlated positively with the number of circulating leukocytes and monocytes. The role of IL-6 in NAFLD was investigated in Il6 knockout (KO) and Il6 receptor A (Il6ra) conditional KO mice after high-fat diet (HFD) feeding. HFD-fed Il6 KO mice had worse liver injury and fibrosis, but less inflammation, compared to wild-type mice. Hepatocyte-specific Il6ra KO mice had more steatosis and liver injury, whereas myeloid-specific Il6ra KO mice had a lower number of hepatic infiltrating macrophages (IMs) and neutrophils with increased cell death of these cells, but greater liver fibrosis (LF), than WT mice. Mechanistically, the increased LF in HFD-fed, myeloid-specific Il6ra KO mice was attributable to the reduction of antifibrotic miR-223 and subsequent up-regulation of the miR-223 target gene, transcriptional activator with PDZ-binding motif (TAZ), a well-known factor to promote NASH fibrosis. In vitro, IL-6 treatment up-regulated exosome biogenesis-related genes and subsequently promoted macrophages to release miR-223-enriched exosomes that were able to reduce profibrotic TAZ expression in hepatocytes by exosomal transfer. Finally, serum IL-6 and miR-223 levels were elevated and correlated with each other in NAFLD patients. Myeloid-specific IL-6 signaling inhibits LF through exosomal transfer of antifibrotic miR-223 into hepatocytes, providing therapeutic targets for NAFLD therapy.

Association of environmental cadmium exposure and bone remodeling in women over 50 years of age

Chronic cadmium (Cd) toxicity is a significant health concern, and the mechanism of long-term low-dose Cd exposure on bone has not been fully elucidated yet. This study aimed to assess the association between long-term environmental Cd exposure and bone remodeling in women who aged over 50. A total of 278 non-smoking subjects from Cd-polluted group (n = 191) and non-Cd polluted group (n = 87) were investigated. Bone mineral density (BMD), the levels of three bone turnover markers (BTMs), including total procollagen type 1 amino-terminal propeptide (P1NP), collagen type 1 cross-linked C-telopeptide (β-CTX), bone-specific alkaline phosphatase (BALP), together with serum soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin (OPG) were determined. Early markers of renal dysfunction were measured as well. Urinary Cd concentrations ranged from 0.41 to 87.31 μg/g creatinine, with a median of 4.91 μg/g creatinine. Age, BMD, T-score, and prevalence of osteoporosis showed no statistical differences among the quartiles of urinary Cd concentrations, while serum levels of P1NP, β-CTX, and OPG were higher in the upper quartiles. Multivariate linear regression models indicated significantly positive associations of urinary Cd concentration with serum levels of P1NP, β-CTX, BALP, sRANKL, and OPG. A ridge regression analysis with T-score and the three BTMs, sRANKL, and OPG, adjusted for age and body mass index (BMI), indicated that except for age and Cd exposure, β-CTX was a predictor of T-score. These findings demonstrated that Cd may directly accelerate bone remodeling. Serum β-CTX might be an appropriate biochemical marker for evaluating and monitoring Cd-related bone loss.Capsule: Cadmium (Cd) may directly accelerate bone remodeling and serum β-CTX is a valuable biochemical marker for evaluating Cd-related bone loss.

Evaluation of serum soluble urokinase plasminogen activator receptor in pediatric community-acquired pneumonia

ObjectiveTo assess the ability of serum soluble urokinase plasminogen activator receptor (suPAR) to predict the severity of pediatric community-acquired pneumonia (CAP).BackgroundCAP is an important cause of pediatric mortality and morbidity. Elevated level of suPAR has been associated with activation of the immune system, and it may be a novel biomarker for pneumonia severity.Patients and methodsA prospective observational study was conducted on a patient group, consisting of 75 patients hospitalized for CAP, in addition to 15 healthy children as a control group. CAP severity was evaluated by Pediatric Respiratory Severity Score. The blood samples were collected within 24 h of hospital admission of patients and for all children in the control group for measurement of suPAR.ResultsThe suPAR level in the patient group was significantly higher than controls [median and range, 3798 pg/ml (395–5694) vs. 395 pg/ml (173–729); P < 0.001]. suPAR level was significantly higher in children with severe pneumonia compared with those having nonsevere pneumonia [median and range, 4430 pg/ml (586.7–5540.3) vs. 3338.5 pg/ml (395–5694.9); P < 0.021]. suPAR was negatively correlated with age, weight, and saturation of peripheral oxygen (rs = 0.31, 0.32, and -0.24, and P = 0.007, 0.004, and 0.041, respectively) but positively correlated with respiratory rate and pulse (rs = 0.24 and 0.26, and P = 0.041 and 0.027, respectively).ConclusionsuPAR is a marker of pediatric CAP and can be used for prediction of CAP severity.

The effect of amiloride in decreasing albuminuria in patients with diabetic kidney diseases: a prospective, crossover, open-label study

Background Diabetic kidney diseases (DKD) were the leading cause of End-stage renal diseases worldwide. Albuminuria was a target for treatment in DKD and decreasing albuminuria was particularly important for improving its prognosis. However, there is still a lack of specific treatment for DKD. Methods We conducted a prospective, crossover, open-label study to investigate the effect of amiloride in patients with DKD. Safety and efficacy were assessed by monitoring urine protein creatinine ratio(uPCR), urinary albumin creatinine ratio (uACR), blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid, serum soluble urokinase-type plasminogen activator receptor (suPAR) and urinary suPAR. Ten subjects were enrolled in the trial. Results In this prospective, crossover, open-label design, amiloride could induce a significant decrease of uACR in DKD. The decrease of serum and urinary suPAR in the amiloride/hydrochlorothiazide (HCTZ) group was also significant compared with those patients using HCTZ as the control group. Correlation analysis showed that the levels of urinary suPAR were positively associated with uPCR and uACR. No significant difference in blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid was seen between the amiloride/HCTZ group and the control group. Conclusion In summary, among patients with DKD, amiloride could decrease albuminuria without severe side effects, which was accompanied by the significant decline of urinary suPAR.

Serum Soluble Receptor for Advanced Glycation End Products in Infants With Bronchiolitis: Associations With Acute Severity and Recurrent Wheeze.

Although bronchiolitis contributes to substantial acute (eg, intensive care use) and chronic (eg, recurrent wheeze) morbidities in young children, the pathobiology remains uncertain. We examined the associations of serum soluble receptor for advanced glycation end products (sRAGE) with acute and chronic morbidities of bronchiolitis including recurrent wheeze. A multicenter, multiyear, cohort study of infants hospitalized for bronchiolitis was analyzed. We measured the serum sRAGE level at hospitalization and its association with intensive care use (use of mechanical ventilation and/or admission to the intensive care unit) and development of recurrent wheeze by age 3 years. We performed causal mediation analysis to estimate indirect (mediation) and direct effects of sRAGE on recurrent wheeze. In 886 infants with bronchiolitis, the median age was 2.9 months. Overall, 15% underwent intensive care and 32% developed recurrent wheeze. In multivariable modeling adjusting for 11 confounders, a higher presenting sRAGE level was associated with lower risk of intensive care (odds ratio for each 1-log increment, 0.39; 95% confidence interval [CI], .16 -.91; P = .03) and significantly lower rate of recurrent wheeze (hazard ratio [HR], 0.58; 95% CI, .36 -.94; P = .03). In mediation analysis, the direct effect was significant (HR, 0.60; 95% CI, .37 -.97; P = .04), while the indirect effect was not (P = .30). Serum sRAGE levels were inversely associated with acute and chronic morbidities of bronchiolitis. The effect of sRAGE on development of recurrent wheeze is potentially driven through pathways other than acute severity of bronchiolitis.

Association analysis of -429T/C receptor for advanced glycation end products (RAGE) gene polymorphism with type 2 diabetic retinopathy and serum soluble RAGE levels in Pakistani patients.

To investigate the association of receptor for advanced glycation end products gene polymorphism 429T/C (rs1800625) with diabetic retinopathy and serum soluble receptor for advanced glycation end products levels in patients with type 2 diabetes. The case-control study was conducted from January 2017 to December 2018 at Pakistan Railway Hospital, Rawalpindi, and the Multidisciplinary Laboratories of Islamic International Medical College, Riphah International University (RIU), Islamabad, Pakistan. Those included were healthy controls in group A, diabetics without retinopathy in group B and patients having diabetic retinopathy in group C. Genotyping for 429T/C was done by tetra-primer amplification refractory mutation system-polymerase chain reaction. Serum soluble receptor for advanced glycation end products levels were measured using enzyme-linked immunosorbent assay. Data was analysed using SPSS 22. Of the 450 subjects, 150(33.3%) were in each of the three groups. The frequency of TT, TC and CC genotypes of 429T/C polymorphism were 137(91.3%), 10(6.7%) and 3(2%) in group A; 133(88.6%), 13(8.7%) and 4(2.7%) in group B; and 127(84.7%), 18(12%) and 5(3.3%) in group C. No significant association of 429T/C genotypic and allelic frequencies were found with groups B and C (p>0.05). Serum soluble receptor for advanced glycation end products levels were significantly high in patients with proliferative diabetic retinopathy and were positively correlated with fasting plasma glucose in group C (p<0.05). TC and CC genotypes were significantly associated with raised serum soluble receptor for advanced glycation end products, and TC with raised fasting plasma glucose in group C. The 429T/C receptor for advanced glycation end products gene polymorphism was found to be associated with severe non-proliferative diabetic retinopathy, and serum soluble receptor for advanced glycation end products levels had a positive correlation with severity of diabetic retinopathy.

Serum soluble tumor necrosis factor receptor (sTNFR) 1 and 2 in STEMI

Tumor necrosis factor-α (TNF-α) interacts with two soluble receptors: TNFR1 and TNFR2. Little is known about the role of sTNFR1 and sTNFR2 in patients with acute ST-segment elevation myocardial infarction (STEMI). Our hypothesis was that the serum levels of sTNFR1 and sTNFR2 might be a marker of the severity of STEMI. We prospectively enrolled 230 consecutive STEMI patients who underwent PCI revascularization in our hospital into a prospective cohort. Blood samples were collected at 5 time points: admission, 4, 24, 48 hours and 1 month after admission (H4, H24, H48, M1). sTNFR1 and sTNFR2 serum levels were assessed using an ELISA assay. Patients underwent cardiac magnetic resonance imaging at M1. Clinical outcomes were recorded over 18 months after STEMI. Mean age of the study population was 59 ± 12 years and 48.5% patients exhibited anterior STEMI. sTNFR1 level significantly increased at H24 with a median of 601.2 pg/mL (interquartile range [IQR] [397.1–896.7]). sTNFR2 level significantly increased at H48 with a median of 2262.3 pg/mL (IQR [1659.6–2862.4]). Patients with sTNFR1 and sTNFR2 peak levels greater than the population median value displayed significantly larger final infarct size and lower LVEF. Patients with peak levels of sTNFR1 and sTNFR2 higher than the population median value were more likely to have an adverse clinical event (MI, stroke, hospitalization for heart failure and all-cause death) during the first 18 months after STEMI (hazard ratio [HR] at 9.0 [3.7–22.2], P = 0.0003 for sTNFR1 and 5.5 [2.1–14.3], P = 0.002 for sTNFR2). Patients with high level of both sTNRF1 and sTNFR2 were at higher risk of adverse clinical event compared to patients with low level (HR = 13.1 [4.4–38.7], P = 0.0005). High levels of circulating sTNFR1 and sTNFR2 were associated with larger infarct size, impaired recovery of LVEF and adverse clinical event in STEMI patients. sTNFR1 and 2 might be useful prognosis markers.

Value of soluble triggering receptor expression on myeloid cells-1 level of alveolar fluid in early diagnosis of ventilator-associated pneumonia: a Meta-analysis

Serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a useful biomarker of bacterial infection. However, the diagnostic value of sTREM-1 of alveolar fluid in pulmonary infection is still unclear. This article aimed to explore the value of sTREM-1 of alveolar fluid in the early diagnosis of ventilator-associated pneumonia (VAP) by systematic review of relevant literatures. CNKI, Wanfang, VIP, PubMed/Medline and Embase databases were retrieved. Articles on diagnosis of VAP by sTREM-1 before June 30, 2019 were collected. QUADAS-2 scale provided by Cochrane Collaboration Network was used to evaluate the quality of diagnostic experiments. RevMan 5.3 and Stata 13.0 software were used to complete Meta-analysis. The levels of sTREM-1 between VAP and non-VAP patients were analyzed by Meta-analysis, and then diagnostic test Meta-analysis was conducted. Heterogeneity, sensitivity and publication bias were analyzed. A total of 24 articles were enrolled. QUADAS-2 scale indicated that the selected literature had low bias and high clinical adaptability. (1) In Meta-analysis of sTREM-1 level in alveolar fluid, 20 articles were selected and found to have high heterogeneity (I2 = 94.4%, P = 0.000). The random effects models were used for Meta-analysis. It was indicated that the sTREM-1 level in alveolar fluid of VAP group was significantly higher than that of non-VAP group with significant difference [standardized mean difference (SMD) was 1.47, 95% confidence interval (95%CI) was 1.00-1.95, Z = 6.14, P = 0.000]. By subgroup analysis and Meta-regression analysis, no source of heterogeneity was found. Sensitivity analysis suggested that the results of this Meta-analysis were robust and credible, and Begg funnel plot analysis showed that there was no significant publication bias (Z = 1.46, P = 0.143). (2) A total of 18 articles were included in the Meta-analysis of diagnostic experiments. Deek funnel plot showed publication bias (P = 0.012). The combined sensitivity was 0.87 (95%CI was 0.81-0.91), specificity was 0.80 (95%CI was 0.73-0.86), and diagnostic odds ratio (DOR) was 26 (95%CI was 13-50). Subgroup analysis of three different sources of alveolar fluid (bronchoalveolar lavage fluid, endotracheal aspiration fluid and exhaled ventilator condensate) showed that STREM-1 had a certain value in early diagnosis of VAP. The I2 of combined DOR was 35.4%, and I2 of sensitivity was 79.46%, I2 of specificity was 77.61%, suggesting heterogeneity in the selected literature. Subgroup analysis found that nationality, subject design, sample source, sample size and diagnostic "gold criteria" were related to heterogeneity, but not age. The area under synthetic receiver operating characteristic (SROC) curve (AUC) was 0.90 (95%CI was 0.87-0.92). The detection of sTREM-1 level in alveolar fluid can be used for the early diagnosis of VAP with high sensitivity and specificity. If combined with other biomarkers, it may have more diagnostic value.

Association between serum soluble receptor for advanced glycation end-products (RAGE) deficiency and severity of clinicopathologic evidence of canine chronic inflammatory enteropathy.

Innate immunity plays a central role in the pathogenesis of chronic inflammatory enteropathies (CIE) in dogs, and further evaluation of the innate immune receptor for advanced glycation end-products (RAGE) is warranted. We measured serum concentrations of decoy receptor soluble RAGE (sRAGE) in 102 dogs diagnosed with CIE, and evaluated relationships with clinical disease severity, histologic lesion severity, concentrations of serum C-reactive protein (CRP), and serum and fecal calprotectin, S100A12, and alpha1-proteinase inhibitor (α1PI). Serum sRAGE levels were not associated with clinical disease activity, serum CRP, serum and fecal α1PI, calprotectin, or S100A12 concentrations. Microscopic lesions in the duodenum were more severe in dogs with serum sRAGE concentration ≤ 340 ng/L (p = 0.013). Serum sRAGE levels were weakly and inversely correlated with the severity of lymphoplasmacytic infiltration in the gastric antrum and duodenum, and with crypt dilation and the neutrophilic infiltrate in the duodenum, in univariate analysis (all p < 0.05), but none of the correlations remained statistically significant after correction for multiple comparisons. Our study confirms that CIE in dogs is associated with decreased serum sRAGE concentrations, suggesting a dysregulated sRAGE/RAGE axis.

Serum soluble urokinase plasminogen activator receptor in adolescents: interaction of chronic pain and obesity.

Obesity in adolescents is increasing in frequency and is associated with short-term and long-term negative consequences that include the exacerbation of co-occurring chronic pain. To determine whether the interaction between chronic pain and obesity would be reflected in changes in serum soluble urokinase plasminogen activator receptor (suPAR) concentrations, a novel marker of systemic inflammation associated with obesity, insulin resistance, and cardiovascular disease. We measured serum suPAR levels in 146 adolescent males and females with no pain or obesity (healthy controls; n = 40), chronic pain with healthy weight (n = 37), obesity alone (n = 41), and the combination of chronic pain and obesity (n = 28). Serum suPAR (median [interquartile range]) was not increased by chronic pain alone (2.2 [1.8-2.4] ng/mL) or obesity alone (2.2 [2.0-2.4] ng/mL) but was increased significantly with the combination of chronic pain and obesity (2.4 [2.1-2.7] ng/mL; P < 0.019). This finding confirms the proposition that pain and obesity are inflammatory states that display a classic augmenting interaction. We propose that measurement of serum suPAR can be added to the armamentarium of serum biomarkers useful in the evaluation of mechanisms of inflammation in adolescent obesity and chronic pain.

P0221SOLUBLE UROKINASE RECEPTOR (SUPAR) IS A PREDICTOR OF DISEASE STATE AND RENAL PROGNOSIS IN PRIMARY NEPHROTIC SYNDROME

Abstract Background and Aims A hypothesis has been proposed that serum (s-) soluble urokinase receptor (suPAR) activates glomerular podocyte β3 integrin to cause podocyte injury and onset of proteinuria in primary nephrotic syndrome (pNS). However, s-suPAR has been questioned as a disease marker for pNS because it did not correlate with urinary protein (UP). Furthermore, there are a few reports that suggested a correlation between urinary (u-) suPAR and UP by univariate analysis, but the correlation between the two has not been studied by multivariate analysis taking confounding factors into account. In addition, it is unclear how u-suPAR is involved in the pathogenesis of pNS. Method In 36 patients with pNS including minimal change (n=18), focal segmental glomerulosclerosis (n=7), membranous nephropathy (n=9) and membranoproliferative glomerulonephritis (n=2), the relationship between u-suPAR (pg/mgCr) and UP (g/gCr) was examined by cross-sectional analysis of baseline values before treatment and longitudinal analysis of changes during the first 2 months of treatment (⊿). In addition, the localization and staining intensity of activated β3 integrin in renal tissue were examined by immuno-histochemistry methods. We also examined whether s-suPAR (pg/ml) or u-suPAR is useful for predicting renal prognosis (1.5-fold increase from baseline in s-Cr) using Cox proportional hazard analysis. Results In cross-sectional analysis, u-suPAR was a UP predictor independent of s-suPAR, eGFR and selectivity index (S.I.) [standardized partial regression coefficient (stdβ) = 0.879, p &amp;lt;0.00001]. Also in the longitudinal analysis, ⊿u-suPAR was a ⊿UP predictor independent of ⊿s-suPAR, ⊿eGFR and S.I. (stdβ = 0.574, p = 0.003). Furthermore, there were significant correlations between u-suPAR and u-L-FABP (r = 0.522, p = 0.001), and between ⊿u-suPAR and ⊿u-L-FABP (r = 0.395, p = 0.017). Activated β3 integrin was mainly detected on proximal tubular brush-border (PTBB), but not glomerular capillaries, moderate to strongly positive in pNS. ⊿s-suPAR was the only predictor of 1.5-fold increase from baseline in s-Cr (Hazard Ratio: 1.361 per 500 pg/ml increase of s-suPAR, p=0.006). Conclusion In pNS, u-suPAR was a proteinuria predictor independent of s-suPAR, suggesting the possibility of the mechanisms of proteinuria through β3 integrin activation in PTBB by u-suPAR. In addition, s-suPAR was useful in predicting renal prognosis.