Serum Levels Of ST2 Research Articles

Relationship between serum IgA levels and low percentage forced expiratory volume in the first second in asthma

Objective: Immunoglobulin A (IgA) is suggested to have pathogenic effects in respiratory inflammatory diseases, including asthma. We aimed to analyze the relationship between serum IgA, and clinical indicators and biomarkers of asthma.Methods: This study was a post hoc analysis of the NHOM Asthma Study. In this study, serum IgA was measured using serum samples stored. We determined an association between the serum IgA level and clinical variables and biomarkers using multivariate linear regression and analyzed the differences in clinical indices between IgA high- and IgA low-asthma.Results: In this study, 572 patients with asthma were included in the final analysis. Lower percentage forced expiratory volume in the first second (%FEV1), higher serum eotaxin levels, lower serum ST2 levels, and higher serum MIP-1β levels, were independently and significantly associated with higher serum IgA levels among asthma patients by multivariate linear regression analysis (%FEV1, 95% confidence interval [CI], −8.18– −0.613, p < 0.05; eotaxin, 95% CI, 8.95–46.69, p < 0.001; ST2, 95% CI, −73.71– −7.37, p < 0.05; and MIP-1β, 95% CI, 1.47–18.71, p < 0.05). Furthermore, IgA high-asthma (serum IgA ≥ 238 mg/dL, n = 270) and IgA low-asthma (serum IgA < 238 mg/dL, n = 302) were compared separately. %FEV1 was significantly lower, the percentage of atopy was higher, and serum MIP-1β level was higher in IgA high-asthma.Conclusions: This study suggests that serum IgA may be involved in the worsening of asthma outcomes, as assessed by %FEV1 and enhanced inflammation via elevated serum MIP-1β.

Abstract 15077: Mitochondrial LonP1 Upregulation in End Stage Heart Failure

Introduction: Mitochondrial dysfunction is a hallmark of heart failure (HF), where correct mitochondrial proteins’ folding is challenged under mitochondrial stress. To restore mitochondrial proteostasis and homeostasis, the mitochondrial unfolded protein response (UPR mt ) is activated, a mechanism not fully elucidated in HF. Purpose: We here investigate the UPR mt induction in advanced/end-stage HF patients requiring Left Ventricular Assist Device (LVAD). In addition, we analyzed the potential influence on clinical outcome. Methods: RNA was extracted from 44 Left Ventricular discs excised during implantation of LVAD from end-stage HF patients and from 5 control LV tissues. Quantitative PCR was performed to assess the relative expression levels of UPR mt machinery ( ATF5, CHOP, mtDNAj, HSP60/10, CLpP and LonP1 ). Immunoblotting was performed to validate mRNA levels. LonP1 subgrouping was performed in reference to LVAD patients’ 3 rd quartile of pre-LVAD Lonp1 mRNA levels. The primary outcome for the Kaplan-Meier survival analysis was all-cause mortality post-LVAD intervention. Results: Gene expression analysis revealed a significant increase in mRNA levels of CHOP and LonP1. Immunoblotting validated the upregulation of CHOP &amp; LonP1 in end-stage HF tissue in comparison to controls. In High-LonP1 patients, we observed a significant increase in left ventricular ejection fraction and blood sodium levels while serum levels of ST-2 and blood urea levels were significantly decreased. High-LonP1 patients had a significantly higher probability of survival post-LVAD intervention and potential to recover myocardial function. Conclusion: This study suggests LonP1 as a potential marker of myocardial recovery and clinical outcome in end-stage heart failure patients treated by LVADs.

Phenotype characterization and biomarker evaluation in moderate to severe type 2-high asthma.

There are two major pathological phenotypes of asthma, type 2 (T2)-high and T2-low asthma, which are important in determining treatment strategies. However, the characteristics and phenotypes of T2-high asthma have not yet been fully identified. This study aimed to identify the clinical characteristics and phenotypes of patients with T2-high asthma. This study used data from a nationwide asthma cohort study in Japan, NHOM Asthma Study. T2-high asthma was defined as a blood eosinophils count ≥ 300 /μL and/or fractional exhaled nitric oxide level ≥ 25 ppb, and the clinical characteristics and biomarkers were compared between T2-high and T2-low asthma. Furthermore, T2-high asthma was phenotyped via hierarchical cluster analysis using Ward's method. Patients with T2-high asthma were older, less likely to be female, had longer asthma duration, had lower pulmonary function, and had more comorbidities, including sinusitis and SAS. Patients with T2-high asthma showed higher serum thymus and activation-regulated chemokine and urinary leukotriene E4 levels and lower serum ST2 levels than those with T2-low asthma. There were four phenotypes among patients with T2-high asthma: Cluster 1 (youngest, early-onset, and atopic), Cluster 2 (long duration, eosinophilic, and low lung function), Cluster 3 (elderly, female-dominant, and late-onset), and Cluster 4 (elderly, late-onset, and asthma-COPD overlap-dominant). Patients with T2-high asthma have distinct characteristics and four distinct phenotypes, in which eosinophil-dominant Cluster 2 is the most severe phenotype. The present findings may be useful in precision medicine for asthma treatment in the future.

IL33 and sST2 serum level in systemic sclerosis microvascular involvement.

Endothelial dysfunction and microvascular damage are hallmarks of systemic sclerosis (SSc). Objective of this study was to evaluate IL33 and ST2 serum levels in SSc patients and healthy controls (HC). Secondary aim was to evaluate the IL33 axis in the SSc microvascular manifestation. IL33 and sST2 have been assessed in 46 SSc patients and 24 HC matched for sex and age. Main clinimetric indexes were assessed. Skin perfusion of hands was evaluated by Laser Speckle Contrast Analysis (LASCA) and echocolordoppler ultrasound of renal arteries was performed to evaluate subclinical renal involvement. SSc patients had higher serum level of IL33 and sST2 than HC. IL33 and sST2 were significantly higher in SSc patient with digital ulcers (DUs) compared to SSc patients without DUs. SSc patients with late nailfold videocapillaroscopy (NVC) pattern had higher serum levels of sST2 than SSc patients with active NVC pattern. SSc patients without proximal-distal gradient (PDG) at LASCA had significantly higher sST2 serum level compared to SSc patients with PDG. SSc patients with renal resistive index (RRI)≥0.70 had higher serum levels of sST2 than SSc patients with RRI<0.70. A positive linear correlation was shown between sST2 and RRI, between sST2 and intrarenal S/D and between sST2 and PI. Kaplan-Meier curves show a significantly reduced free survival from DUs in patients with increased sST2 (p=0.025). In multivariate analysis, sST2 is associated with the development of new DUs. IL33 and sST2 are increased in SSc patients and ST2 might be a marker of microvascular damage.

THE ROLE OF NT-PROBNP AND ST2 BIOMARKERS IN PATIENTS WITH ACUTE CORONARY SYNDROME

The aim: To determine the diagnostic value of serum levels of ST2 in patients with the acute coronary syndrome (ACS) and its correlation with NT-proBNP levels. Materials and methods: NT-proBNP and ST2 concentration in serum of patients was measured on admission to the hospital and on the 10th day of the treatment using NT-proBNP ELISA (Biomedica, Slovakia) and Presage ST2 assay (Critical Diagnostics, USA), respectively. Results: Statistically significant direct correlations (p&lt;0.05). The simultaneous increase of ST2 and NT-proBNP serum levels above their threshold in patients with ACSelST (sensitivity – 92.5 %, specificity – 74.2 %, AUC – 0.893, р&lt;0.05) indicated a significant risk of cardiovascular (CV) complications of acute myocardial infarction (AMI) during the inpatient period, e.g. acute heart failure, acute LV aneurysm, recurrent AMI, as well as rhythm and conductivity disturbances. Conclusions: The data suggest that both ST2 and NT-proBNP may prove useful in predicting unfavorable prognosis during the inpatient care of AMI, as the simultaneous increase of these biomarkers above their threshold values indicates a significant risk of CV complications.

Association of soluble ST2 and infarct location within 12–24 h in STEMI: A cross-sectional study

BackgroundST-Segment Elevation Myocardial Infarction (STEMI) causes the release of soluble ST2 biomarkers at high level on acute phase. However, sST2 has never been used as adjunct biomarker in ESC/AHA guideline for STEMI. Furthermore, the specific onset that sST2 may have role in acute phase of STEMI related with infarct location has not been established. This study aimed to prove the association between serum ST2 levels and infarct location in STEMI. Material and methodsThis study was cross-sectional. STEMI patients with onset of anginal pain 12–24 h were included in study. The exclusion criterias were patients with AMI aside from STEMI and other potential confounders affecting the sST2 level. Serum sST2 was collected on first medical contact when admitted to emergency unit. The patients were grouped into anterior STEMI and non-anterior STEMI. sST2 levels were compared with demographics data, clinical and laboratory variables using Student's t-test. Correlation of sST2 levels was analyzed using Spearman's correlation coefficient. Results19 subjects were included in the anterior STEMI and 20 subjects were included in the non-anterior STEMI. We found no difference in sST2 levels between anterior STEMI and non-anterior STEMI (mean ± SD; 729.97 pg/mL ± 147.78 pg/mL vs 606.87 pg/mL ± 147.78 pg/mL, p = 0.119). Onset was correlated with serum sST2 levels in male subjects (r = −0.459, p = 0.012). We found significant difference of mean sST2 between 2 onset groups divided at median (12–18 h vs 19–24 h, Δ mean = 107.75 pg/mL, p-value = 0.021). ConclusionsST2 was not associated with infarct location within 12–24 h onset of STEMI. This results suggest that infarct location might not responsible for the elevation of serum sST2 levels in acute phase of STEMI.

Role of stimulating growth factor 2 and galectin-3 in predicting the ventricular tachyarrhythmias in patients with ischemic cardiomyopathy

Aim. To assess the role of stimulating growth factor 2 (ST-2) and galectin-3 in predicting the ventricular tachyarrhythmias (VTA) in patients with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) &lt;35%.Material and methods. The study included 40 patients (men, 36 (90,0%); median age, 64,5 [57,5; 68,5] years) with CAD, NYHA class IIIII heart failure, LVEF &lt;35%, indications for implantable cardioverter defibrillator (ICD) (primary prevention of sudden cardiac death). Prior to ICD implantation, patients were measured for serum ST-2 and galectin-3 levels. For 18 months, patients were assessed for arrhythmic events recorded in the ICD memory.Results. The 1st group consisted of 10 (25,0%) patients who had VTA episodes, arrested by antitachycardia pacing or shock during 18-month follow-up. The 2nd group consisted of 30 (75,0%) patients without VTA episodes. It was found that ST-2 concentration &gt;22,48 ng/ml (p=0,02) and galectin-3 &gt;10,95 ng/ml (p=0,009) corresponded to appropriate ICD discharge. Multivariate ROC analysis demonstrated that the only independent predictor of VTA was ST-2 elevation (odds ratio, 1,11; 95% CI, 1,01-1,21; p=0,023).Conclusion. An increase in the concentration of both ST-2 &gt;22,48 ng/ml and galectin-3 &gt;10,95 ng/ml had a high predictive value in assessing the VTA risk in patients with ischemic cardiomyopathy. In multivariate analysis, an increase in ST-2 &gt;22,48 ng/ml was an independent predictor of VTA.

Diagnostic value of the N-terminal pro-brain natriuretic peptide and stimulating growth factor in patients with acute coronary syndrome

Aim. To determine levels of stimulating growth factor (ST2) and its correlation with levels of N-terminal pro-brain natriuretic peptide (Nt-proBNP) in patients with acute coronary syndrome (ACS).Materials and methods. 186 patients with admitting diagnosis of ACS were examined (81 with ST-elevation myocardial infarction (STEMI) and 86 with non ST-segment myocardial infarction (NSTEMI)). For futher investigation we choose 25 patients (mean age 61,67±1,13) with STEMI (group I) and 24 patients (mean age 61,80±1,13) with NSTEMI (group II). In serum of those patients we determined levels of NT-proBNP and ST2 on days 1 and 10 of hospitalisation using a commercial assays (Biomedica, Slovakia and Critical Diagnostics, USA respectively).Results. On the day 1 of hospitalisation patients with STEMI showed higher serum levels of NT-proBNP (779,41±57,86 pg/ml (I)) in comparison with NSTEMI group (588,96±82,47pg/ml (II)) (р&gt;0,05). On the day 10th of hospitalisation mean levels of NT-proBNP were 369,75±55,22 pg/ml (І) and 139,95±19,57 pg/ml (ІІ) respectively (p&lt;0,01). Level of ST2 was significantly increased in the serum of patients with STEMI on the day 1 of hospitalisation as compared with NSTEMI group (111,71±12,41 ng/ml (I) and 77,58±6,5 ng/ml (ІІ), р&lt;0,05) respectively. On day 10th of hospitalisation in serum of patient from group I ST2 levels were 33,43±4,38 ng/ml whereas in participants from group II ST2 levels were 30,20±2,05 ng/ml (р&gt;0,05). We have shown a strong linear correlation between serum levels of ST2 and NT-proBNP in patients with STEMI (I) on first and 10th days of hospitalisations (r=0,43 and r=0,85; p&lt;0,05 respectively). In group II levels of those markers correlates considerably weaker (r=0,35 and r=0,01; p&gt;0,05).Conclusions. Increased level of NT-proBNP corresponds to the size of necrotic area in myocardial infarction, whereas level of ST2 correlates with severity of heart insufficiency symptoms by ACS. Increased levels of both ST2 and NT-proBNP allows to predict disease progression and possible complications

ST2 Predicts Risk of Unplanned Readmission Within 1 Year After Pediatric Congenital Heart Surgery

Approximately 10% to 20% of children are readmitted after congenital heart surgery. Very little is known about biomarkers as predictors of risk of unplanned readmission after pediatric congenital heart surgery. Novel cardiac biomarker ST2 may be associated with risk of unplanned readmission. ST2 concentrations are believed to reflect cardiovascular stress and fibrosis. Our objective was to explore the relationship between pre- and postoperative ST2 biomarker levels and risk of readmission within 1 year after congenital heart surgery. We prospectively enrolled pediatric patients aged < 18 years who underwent at least 1 congenital heart operation at Johns Hopkins Hospital from 2010 to 2014. Plasma samples were collected immediately before surgery and at the end of bypass. We used Kaplan-Meier survival analysis and multivariable Cox regression models to adjust for variables used in The Society of Thoracic Surgeons Congenital Heart Surgery Database mortality risk model. Of our cohort of 145 patients, we found 39 children with readmissions within 365 days. The median time to unplanned readmission was 54 days (interquartile range, 10-153). Kaplan-Meier analysis demonstrated a significant difference across terciles of pre- and postoperative ST2 biomarker levels. After adjustment, elevated serum levels of ST2 measured preoperatively and postoperatively were associated with increased risk of readmission (hazard ratio, 2.5-3.7; all P < .05). Elevated levels of ST2 are significantly associated with increased risk of unplanned readmission within 1 year after pediatric congenital heart surgery. Novel serum biomarker ST2 can be used for risk stratification or estimating postsurgical prognosis.

Combining Novel Biomarkers for Risk Stratification of Two-Year Cardiovascular Mortality in Patients with ST-Elevation Myocardial Infarction.

ST-elevation myocardial infarction (STEMI) is one of the main reasons for morbidity and mortality worldwide. In addition to the classic biomarker NT-proBNP, new biomarkers like ST2 and Pentraxin-3 (Ptx-3) have emerged as potential tools in stratifying risk in cardiac patients. Indeed, multimarker approaches to estimate prognosis of STEMI patients have been proposed and their potential clinical impact requires investigation. In our study, in 147 patients with STEMI, NT-proBNP as well as serum levels of ST2 and Ptx-3 were evaluated. During two-year follow-up (FU; 734.2 ± 61.2 d) results were correlated with risk for cardiovascular mortality (CV-mortality). NT-proBNP (HR = 1.64, 95% CI = 1.21–2.21, p = 0.001) but also ST2 (HR = 1.000022, 95% CI = 1.00–1.001, p < 0.001) were shown to be reliable predictors of CV-mortality, while the highest predictive power was observed with Ptx-3 (HR = 3.1, 95% CI = 1.63–5.39, p < 0.001). When two biomarkers were combined in a multivariate Cox regression model, relevant improvement of risk assessment was only observed with NT-proBNP+Ptx-3 (AIC = 209, BIC = 214, p = 0.001, MER = 0.75, MEV = 0.64). However, the highest accuracy was seen using a three-marker approach (NT-proBNP + ST2 + Ptx-3: AIC = 208, BIC = 214, p < 0.001, MER = 0.77, MEV = 0.66). In conclusion, after STEMI, ST2 and Ptx-3 in addition to NT-proBNP were associated with the incidence of CV-mortality, with multimarker approaches enhancing the accuracy of prediction of CV-mortality.

The Correlation between sST2 and Atrial Fibrillation and Its Clinical Significance

Objective: To explore the level of soluble growth-stimulated expression gene 2 (sST2) in patients with atrial fibrillation (AF) and its relationship with atrial remodeling. Methods: From December 2018 to July 2019, 86 patients were enrolled in the cardiovascular department of Jingzhou Central Hospital in Hubei Province. AF group was 60 patients with AF diagnosed according to the diagnostic criteria of electrophysiology and pacing branch of Chinese Medical Association, while the control group was 26 normal ECG patients with sinus rhythm examined by ECG and/or DCG. Clinical data, NT proBNP and birth rate of all patients were collected chemical indicators. All the patients in the groups were examined by ECG and color Doppler echocardiography. The serum level of ST2 was detected by enzyme-linked immunosorbent assay (ELISA), and the indexes related to atrial remodeling in echocardiography, left atrial diameter (LAD), were collected, compared and analyzed. Results: Serum sST2 levels and LAD and RAD values in the AF group were higher than those in the control group (P < 0.05 or P < 0.01). Serum sST2 levels were higher in the AF group than in the paroxysmal atrial fibrillation group (P = 0.031). 1) The sST2 level was positively correlated with LAD and RAD measured by cardiac ultrasound (r = 0.388, P = 0.029). Conclusion: Serum sST2 levels have early recognition value in patients with high-risk atrial fibrillation, which contributes to the stratification of risk of atrial fibrillation and the prediction of disease activity. Elevated serum sST2 levels may be associated with atrial remodeling. sST2 may be an objective biomarker that predicts the risk of emergency admission in patients with atrial fibrillation. Elevated sST2 levels may be associated with atrial fibrillation progression.

Association of Soluble ST2 Serum Levels With Outcomes in Pediatric Dilated Cardiomyopathy

BackgroundPrognosis in patients with pediatric dilated cardiomyopathy (PDCM) is urgently required to identify high-risk patients. Elevated soluble ST2 (sST2) is associated with prognosis in adult patients with heart failure. This study aimed to assess the prognostic value of sST2 in PDCM. MethodsNinety-four patients with PDCM were enrolled after admission from 2 centres in China and followed up for adverse events (death, cardiac transplantation, and heart-failure–related rehospitalization). B-type natriuretic peptide (BNP) and sST2 levels were measured. ResultsOver a median of 678 (interquartile range [IQR]: 533-785) days, 28 (29.8%) adverse events occurred. Patients in the highest tertile of sST2 levels had increased risk of short-term (< 6 months) (adjusted hazard ratio [HR]: 8.36, 95% confidence interval [CI], 1.02-73.52; P < 0.05) and long-term adverse events (2 years) (adjusted HR: 4.23; 95% CI, 1.32-13.60; P < 0.01) than those in lower tertiles. The C-statistic was increased with addition of sST2 to BNP from 0.697 (95% CI, 0.541-0.852) to 0.812 (95% CI, 0.697-0.939) for short-term and from 0.712 (95% CI, 0.604-0.819) to 0.798 (95% CI, 0.697-0.899) for prediction of long-term adverse events. An intermediate-risk subgroup was identified, and 24% had adverse events. When serial measurements were taken in a nested case-control subgroup, sST2 levels were constantly high in patients with late adverse events (> 6 months) but gradually decreased in nonadverse-event controls compared with 3-month and 6-month baseline levels. ConclusionsIn patients with PDCM, serum sST2 levels are associated with adverse events and have robust prognostic value. Serial measurements of sST2 could help in managing patients for monitoring outcomes of treatment.

Acute Graft-Versus-Host Disease (aGVHD, Non-Relapse Mortality) Risk Prediction Assay: Validation and Initial Reference Lab Experience

Introduction aGVHD affects 40% to 60% of hematopoietic cellular transplant (HCT) patients, targeting the skin, liver, and gastrointestinal tract with a median onset approximately 1 month after transplant. In 2017, an interpretive algorithm based on serum ST2 and REG3α levels was clinically validated (JCI Insight 2017;2(3):e89798). Objectives This report details validation, inter-lab correlation and initial results from clinical analysis. Methods ST2 and REG3α levels were analyzed in serum using enzyme immunoassays. ST2 and REG3α values are analyzed through an equation to provide an index value that can be used for predicting non-relapse mortality and aGVHD risk for pre-symptomatic (low/high risk), symptomatic onset (low/medium/high risk) and post treatment (low/high risk) HCT patients. Results were compared with the research lab where the equation was established (Mount Sinai Medical Center, MSMC). Results The inter-assay precision ranged from 12 to 26 %CV for ST2 and REG3a, while those for the calculated indices ranged from 17 to 18%. Accuracy was compared against biomarker values and indices reported by MSMC for 106 serum samples. Among samples with biomarker concentrations within the assays' measuring range, the relative error was Conclusions The aGVHD index and its component input assays, ST2 and REG3a, were validated for clinical use. Notably, excellent concordance was observed on a large sample set (106 sera) with MSMC. In addition, initial results indicate that the aGVHD index may prove useful for risk-stratifying HCT patients.

Serum levels of interleukin 33 and its receptor ST2 in patients treated with subcutaneous allergen immunotherapy in intermittent allergic rhinitis.

IntroductionInterleukin 33 (IL-33) is a pleiotropic cytokine involved in pathological processes in seasonal allergic rhinitis. IL-33 binds to ST2 receptor, which is highly expressed on mast cells and selectively on Th2 cells. Information is lacking on the role of IL-33/ST2 axis in allergen subcutaneous immunotherapy.Aim of the studyTo determine if allergen immunotherapy changes the IL-33/ST2l axis in seasonal allergic rhinitis patients.Material and methods40 patients with intermittent allergic rhinitis sensitive to grass and/or tree pollen were studied. Among these, 10 patients were longitudinally assessed in the follow-up visit after completing the first course of immunotherapy. Twenty-two healthy subjects were included as controls. Immunotherapy was applied according to a perennial schedule comprising up-building and maintenance phases. Serum levels of ST2/IL-33 R and IL-33 were measured by ELISA (R&D Systems).ResultsSerum levels of IL-33 significantly rose after the first course of immunotherapy and reached the controls levels. Serum levels of ST2 were comparable before the pollen season and after the first course of immunotherapy.ConclusionsIncrease in serum levels of IL-33 after the first course of immunotherapy may suggest it is too short period to prevent the expected raise in serum IL-33 levels in the pollen season, and longer treatment is required to observe significant changes of this cytokine. ST2 serum levels are independent of immunotherapy and pollen season.

Different ST2 Serum Concentrations in Asymptomatic and Symptomatic Carotid Artery Stenosis

ST2 represents an interesting biomarker associated with the progression of atherosclerotic disease. This study aims to detect different ST2 serum concentrations, and intraplaque ST2 expression, in patients with symptomatic and asymptomatic carotid artery stenosis. The analysis of ST2 expression in the atheromatous plaque did not show any significant difference between symptomatic and asymptomatic patients (39.61±35.97 vs. 38.49±35.26; P=ns). ST2 serum concentrations of asymptomatic and symptomatic patients were statistically different with a concentration of 11.04±8.95ng/mL and 13.91±8.01ng/mL, respectively (P=0.037). We observed statistical difference in serum ST2 levels between asymptomatic and symptomatic patients for cerebrovascular acute disease. No differences have been obtained in intraplaque ST2 expression. Soluble serum ST2 levels can be a useful biomarker to identify patients at risk for cerebrovascular events.

P4734The impact of ST2 serum levels on endothelial function and peripheral vascular resistance in patients with heart failure

P4734The impact of ST2 serum levels on endothelial function and peripheral vascular resistance in patients with heart failure

A functional IL1RL1 variant regulates corticosteroid-induced sST2 expression in ulcerative colitis

The ST2/IL33 signalling pathway has been associated with ulcerative colitis (UC). ST2, encoded by the IL1RL1 gene, is expressed as both a membrane-anchored receptor (ST2L) activated by IL33 and as a soluble receptor (sST2) with anti-inflammatory properties. In UC patients, sST2 is further increased by corticosteroid treatment; however, the glucocorticoid-mediated molecular regulation remains unknown. We therefore tested whether genetic variants in the IL1RL1 distal promoter are involved in UC and affect glucocorticoid-mediated ST2 expression. Serum ST2 levels and genetic variants in the IL1RL1 distal promoter were examined by ELISA and PCR sequencing in UC patients receiving corticosteroids. Glucocorticoid-mediated ST2 production was evaluated in intestinal mucosa cultures. Molecular regulation of glucocorticoid-mediated ST2 was assessed by RT-qPCR, ChIP assay and luciferase reporter assay. Dexamethasone effect on ST2 transcript expression was analyzed in leukocytes and related to IL1RL1 variants. Sequencing of a distal IL1RL1 promoter region demonstrated that SNPs rs6543115(C) and rs6543116(A) are associated with increased sST2 in UC patients on corticosteroids. Dexamethasone up-regulated sST2 transcription through interaction with the glucocorticoid-response element (GRE) carrying rs6543115(C) variant. Our data indicate that IL1RL1 SNPs rs6543115(C) confer susceptibility to UC and is contained in the GRE, which may modulate glucocorticoid-induced sST2 expression.

Roles of ST2, IL-33 and BNP in predicting major adverse cardiovascular events in acute myocardial infarction after percutaneous coronary intervention.

This study investigated roles of serum ST2, IL‐33 and BNP in predicting major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Blood samples were collected from the included AMI patients (n = 180) who underwent PCI. All patients were divided into the MACEs and MACEs‐free groups. Enzyme‐linked immunosorbent assay was performed to measure serum levels of ST2, IL‐33 and BNP. Severity of coronary artery lesion was evaluated by Gensini score. Pearson correlation analysis was used. A receiver operating characteristics curve was drawn to evaluate the potential roles of ST2, IL‐33 and BNP in predicting MACEs, and Kaplan–Meier curve to analyse the 1‐year overall survival rate. Logistic regression analysis was conducted to analyse the independent risk factors for MACEs. Compared with the MACEs‐free group, the serum levels of ST2, IL‐33 and BNP were significantly higher in the MACEs group. Serum levels of ST2, IL‐33 and BNP were positively correlated with each other and positively correlated with Gensini score. The area under curves of ST2, IL‐33 and BNP, respectively, were 0.872, 0.675 and 0.902. The relative sensitivity and specificity were, respectively, 76.27% and 85.92%, 69.49% and 58.68%, as well as, 96.61% and 77.69%. Serum levels of ST2, IL‐33 and BNP were independent risk factors for MACEs. The 1‐year overall survival rate was higher in AMI patients with lower serum levels of ST2, IL‐33 and BNP. In conclusion, serum levels of ST2, IL‐33 and BNP have potential value in predicting MACEs in AMI patients undergoing PCI.

Serum Soluble ST2 and Diastolic Dysfunction in Hypertensive Patients.

Background Echocardiographic evaluation of left ventricular (LV) structural and functional alterations in hypertension has some limitations, potentially overcome by using biomarkers. ST2, a prognostic biomarker for heart failure and myocardial infarction patients, was less studied in hypertension. Aim To analyze the relationship between serum ST2 levels and diastolic dysfunction (DD) in hypertension. Method We enrolled 88 hypertensive outpatients (average age 65 years, 69.3% females) in a prospective study, stratified for presence of LV hypertrophy (LVH). For each patient clinical examination, lab workup (routine and serum ST2 levels) and echocardiography were performed. Results Hypertensive patients with LVH had higher age, pulse pressure, mean arterial pressure, and serum ST2, while having lower serum albumin than those without LVH. Serum ST2 levels correlate with parameters of LV remodeling and DD. We found that 5.3% of ST2 level variability was caused by a 1-unit variation of cardiovascular risk. We identified cut-off values for discriminating hypertension with LVH versus that without LVH and grade 2 DD versus normal diastolic performance. Conclusion ST2 could be used as diagnostic biomarker for cardiac remodeling and altered diastolic performance in hypertension, providing additional data to echocardiography. It could represent a milestone in early detection of cardiac performance alteration.

ST2 DI INFARK MIOKARD AKUT

Acute Myocardial Infarction (AMI) is a major problem threatening Indonesian inhabitants as well as in many countries. Each year AMI patients are increasing. ST2 is a novel cardiac marker for the diagnosis and prognosis of acute myocardial infarction. The purpose of this study was to know and find the diagnostic value of ST2 serum in patients with AMI. This cross sectional study was conducted on 46 patients who had chest pain as the main complaint in the Emergency Department, Dr. Soetomo Hospital, Surabaya between April 20 to July 20, 2013. The sera were examined for ST2, cTn-T, the diagnostic value was determined using the acute myocardial infarction clinical criteria according to the Universal Definition of Myocardial Infarction (2007) as the gold standard. The results of ST2 serum levels measurement showed a sensitivity of 83% and specificity of 70% at a cut-off value of ST2 16.64 ng/mL and AUC 0.878, p=0.000. The concordance examination between using cTn-T levels and ST2 was 48.1%. A significanct correlation was obtained with a correlation coefficient r=0.489, p=0.001 between the levels of cTn-T and ST2. Based on this study, the ST2 serum levels can be used for screeningto aid the diagnosis of acute myocardial infarction. However, there is a weak correlation and concordance between cTn-T with ST2. Thus, the researchers need a further study to determine the diagnostic value of ST2 for the detection of acute myocardial infarction.