Serum sST2 Levels Research Articles

Prognostic Significance of Serum Interleukins and Soluble ST2 in Traditional Chinese Medicine (TCM) Syndrome-Differentiated Rheumatoid Arthritis.

BackgroundsThe aim of this study was to explore the possible correlations of serum interleukins and soluble ST2 (sST2) protein with clinical features and inflammatory cytokines in rheumatoid arthritis (RA) patients, as well as to assess ability of TCM (Traditional Chinese Medicine) syndromes to differentiate RA patients and evaluate prognosis.Material/MethodsThirty RA patients and 25 healthy individuals were enrolled. Syndrome activity was evaluated, and lab tests were performed. Serum levels of IL-10, IL-17, IL-33, and sST2 were assessed by ELISA.ResultsSerum levels of sST2, IL-33, and pro-inflammation cytokine IL-17 were all up-regulated, while the immunosuppressive cytokine IL-10 was decreased in RA patients. Serum IL-33 level was positively associated with ESR, CRP, and RF, as well as with HAQ score, VAS score, and DAS28 scores (P<0.05). Serum sST2 level was correlated with the morning stiffness time and ESR, as well as scores of HAQ and DAS28 (P<0.05). In addition, IL-33 level was positively corelated with IL-17 (r=0.83, P<0.01) and the relative ratio of IL-10/IL-17 (r=0.904, P<0.01), and was negatively related with IL-10 (r=−0.632, P<0.01). TCM syndrome differentiation was conducted for RA patients, including the hot syndromes and cold syndromes groups. Hot syndromes RA patients had significantly more severe inflammation compared with cold syndromes patients.ConclusionsIL-33 is a possible index for monitoring disease activity and inflammation condition in RA. IL-33 contributes to RA pathogenesis through unbalancing IL-10 and IL-17. In terms of TCM, hot syndromes RA presented more serious inflammation and more active disease activity, indicating a poorer prognosis.

Increased serum levels of IL‐33 and soluble ST2 in neonates with human cytomegalovirus infection

Interleukin 33 (IL-33) and soluble form of ST2 (sST2) are involved in inflammation. This study aimed to assess the role of serum IL-33 and sST2 in neonates with HCMV infection. The concentration of serum IL-33 and sST2 in 20 patients and 16 healthy controls were measure by enzyme-linked immune-sorbent assay (ELISA). The clinical and laboratory data were described. Our results showed serum sST2 and IL-33 levels were significantly higher in the HCMV group than the control group. Significant positive correlation was observed between sST2 and IL-33 (r = 0.518, P = 0.001). Furthermore, there was a positive, moderate, and statistically significant correlation between sST2 and ALT levels in the control and HCMV groups (r = 0.579, P = 0.007; r = 0.66, P = 0.005, respectively). The AUC of sST2 and IL-33 was found to be 0.822 and 0.867 respectively. Further, at a cut-off value of 1823.4 ng/mL, sST2 gave 65% sensitivity and 93.7% specificity. Similarly, IL-33 gave 95% sensitivity and 68.7% specificity at a cut-off value 2.04 pg/mL. The Youden index of sST2 and IL-33 was found to be 0.587 and 0.637, respectively. In conclusion, this study revealed that sST2 and IL-33 have great potential to be used as biomarkers for early screening and indicate liver damage for HCMV patients in future after validation in large cohort study.

Value of serum soluble ST2 in predicting the prognosis of sepsis

Objective To study the predictive value of serum soluble ST2 (sST2) in patients with sepsis. Methods A total of 63 patients with sepsis and 30 healthy subjects as a control group were enrolled in the study. Serum sST2 concentrations were measured by ELISA method. Patients were divided into sepsis group (n=44) and septic shock group (n=19). According to 28-day mortality after the diagnosis of sepsis, patients were divided into death group (n=18) and survival group (n=45). Respiratory rate, oxygenation index, white blood cell count, procalcitonin (PCT), C reactive protein (CRP), serum creatinine (CRE), total bilirubin (TBIL) of patients and control subjects were measured. SPSS 23.0 software was used for the statistical analyses. The measurement data was analyzed by t test and the enumeration data was analyzed by chi square test. The survival status was analyzed by Logistic binary regression analysis and ROC curve analysis. Results The serum sST2 level (1 382.12±384.07) pg/mL in sepsis group was significantly higher than that in control group (569.28±163.46) pg/mL (P<0.05). in septic shock group, 28-day mortality rate (63.16%) and serum sST2 level (1 675.49±457.59) pg/mL was higher than those in sepsis group (13.64%) (1255.44 ± 265.70) pg/ml (P<0.05). The PCT (16.37±16.36 ) ng/mL and serum sST2 level (1 794.47±335.18)pg/mL in death group were higher than those in survival group (P<0.05). The ROC curve showed that the AUC of sST2 was larger than that of PCT (0.917 vs. 0.884), the sensitivity was higher than that of PCT (88.9% vs. 72.2%), and the specificity was lower than that of PCT (82.2% vs. 93.3%). The combination AUC of sST2 and PCT was 0.944. Conclusions Serum sST2 has a certain value in the diagnosis of sepsis, and can be used to predict the prognosis of patients with sepsis. The higher the sST2 value, the worse the prognosis. Compared with PCT, sST2 is more sensitive in the prognosis of sepsis, but the specificity is not high enouph. The measurement of sST2 level coupled with PCT level may be more useful. Key words: Sepsis; Septic shock; Soluble ST2; Interleukin-33; Inflammatory factors; Procalcitonin; Diagnosis; Prognosis

Fibrosis Marker Soluble ST2 Predicts Atrial Fibrillation Recurrence after Cryoballoon Catheter Ablation of Nonvalvular Paroxysmal Atrial Fibrillation.

Background and ObjectivesWe aimed to investigate the relationship between the recurrence of atrial fibrillation (AF) and fibrosis marker soluble ST2 (sST2) in patients with nonvalvular paroxysmal AF (PAF).MethodsWe prospectively included 100 consecutive patients with PAF diagnosis and scheduled for cryoballoon catheter ablation for AF (47 males, 53 females; mean age 55.1±10.8 years). sST2 plasma levels were determined using the ASPECT-PLUS assay on ASPECT Reader device (Critical Diagnostics). The measurement range of these measurements was 12.5–250 ng/mL. Patients had regular follow-up visits with 12-lead electrocardiogram (ECG), medical history, and clinical evaluation. Twenty-four hours Holter ECG monitoring had been recorded 12 months after ablation.ResultsAF recurrence was detected in 22 patients after 1 year. Age, smoking history, diabetes mellitus,hypertension frequency, angiotensin converting enzyme inhibitor-angiotensin receptor blocker use, CHA2DS2VASc and HAS-BLED scores, serum sST2 level, left atrium (LA) end-diastolic diameter, LA volume and LA volume index were related to AF recurrence. In multivariable logistic regression analysis, sST2 was found to be only independent parameter for predicting AF recurrence (odds ratio, 1.085; p=0.001). Every 10-unit increase in sST2 was found to be associated with 2.103-fold increase in the risk of AF recurrence. The cut-off value of sST2 obtained by receiver operating characteristic curve analysis was 30.6 ng/mL for prediction of AF recurrence (sensitivity: 77.3%, specificity: 79.5%). The area under the curve was 0.831 (p<0.001).ConclusionssST2, which is associated with atrial fibrosis, can be thought to be a useful marker for detection of patients with high-grade fibrosis who will get less benefit from cryoablation.

Increased soluble ST2 and IL‑4 serum levels are associated with disease severity in patients with membranous nephropathy.

The interleukin (IL)‑33/suppression of tumorigenicity2(ST2) axis regulates Th2 reactivity, and ST2 is the receptor for IL‑33. In this study, the roles of IL‑33 and soluble ST2(sST2) in the pathogenesis of membranous nephropathy(MN), and their association with disease severity were evaluated. Serum levels of IL‑33 and sST2 in 93patients, and 34healthy controls (HCs) were measured by enzyme‑linked immunosorbent assays. Clinical characteristics were recorded and the estimated glomerular filtration rates (eGFRs) were computed. In addition, the association between serum IL‑33 and sST2 levels, and clinical measurements in patients with MN was analyzed. No difference in the serum levels of IL‑33 was identified between the patients with MN and HCs. However, the serum levels of sST2 were considerably higher in the MN patients compared with in the HCs at every stage. Higher concentrations of serum IL‑2, IL‑4, IL‑10, IL‑17A, and IFN‑γ were measured in the MN patients compared with in the HCs. Serum sST2 concentrations were negatively correlated with IL‑4 concentrations in the patients with MN. Furthermore, serum sST2 levels were negatively correlated with the eGFRs and serum calcium levels. Serum sST2 levels, but not IL‑33 levels, were positively correlated with the 24‑h urine protein and serum phosphorus levels. Following treatment, serum sST2 levels were considerably reduced, whereas serum IL‑4 and IL‑10levels were significantly increased. These data suggest that sST2 and IL‑4, but not IL‑33, contribute to the pathogenesis of MN.

Prognostic Factor of Soluble ST2 Serum on 90 Days-Major Cardiovascular Events in ST-Elevation Acute Myocardial Infarction Patients with Reperfusion Therapy

Background: Soluble ST2 (sST2) is released by strained myocardial. High baseline sST2 levels have been shown to be a predictor of mortality and heart failure in STEMI patients within 30 days and within 1 year, but its effect on medium-term events has not been widely investigated. Aims: To assess the prognostic factor of sST2 levels during admission with major cardiovascular events in the form of cardiovascular death and heart failure due to left ventricular dysfunction within 90 days of observation. Methods: A retrospective cohort study was conducted on STEMI patients with an onset of ≤ 24 hours undergoing reperfusion therapy from April 2014 - June 2015 in Dr. Sardjito General Hospital, Yogyakarta, Indonesia. The sST2 sample of venous blood was performed at admission. Primary outcomes for this analysis included cardiovascular death and congestive heart failure (CHF) through 90 days of follow-up. Assessment of major cardiovascular events was based on medical record data. Bivariate analysis were conducted on demographic and clinical factors related to sST2 and major cardiovascular events. A multivariate analysis was then conducted to determine the independent factors that influenced the emergence of major cardiovascular events. Results: Of the 107 patients who met the subject criteria, there were 33 (30.8%) subjects withmajor cardiovascular events and 74 subjects (69.2%) without major cardiovascular events in 90 days of observation. Of the 33 subjects with major cardiovascular events, there were 10 subjects (9.3%) died and 23 subjects (21.5%) with heart failure. The sST2 levels did not have a significant relationship with the incidence of mortality (p=0.617), heart failure (p=1.000), orboth combined (p = 1.000) in 90 days of observation. Conclusion: High serum sST2 levels during admission in STEMI patients who had undergonereperfusion therapy were not associated with increased incidence of major cardiovascular events (either the incidence of mortality or heart failure alone or both combined) in 90 days observation.

Association of interleukin 1 receptor-like 1 gene polymorphisms with eosinophilic phenotype in Japanese adults with asthma.

IL1RL1 (ST2) is involved in Th2 inflammation including eosinophil activation. Single nucleotide polymorphisms (SNPs) of the IL1RL1 gene are associated with asthma development and increased peripheral blood eosinophil counts. However, the association between IL1RL1 SNPs and eosinophilic phenotype among adults with asthma remains unexplored. In a primary cohort of 110 adult Japanese patients with stable asthma, we examined the associations between IL1RL1 SNPs and clinical measurements including forced expiratory volume (FEV1), airway reversibility of FEV1, exhaled nitric oxide (FeNO), serum soluble-ST2 (sST2) levels, peripheral blood eosinophil differentials and serum total IgE level. The findings in the primary cohort were confirmed in a validation cohort of 126 adult Japanese patients with stable asthma. Patients with minor alleles in 3 SNPs (rs17026974, rs1420101, and rs1921622) had high FeNO, blood eosinophil differentials, and reversibility of FEV1, but low levels of serum sST2 and FEV1. Minor alleles of rs1041973 were associated with low serum sST2 levels alone. In the validation cohort, minor alleles of rs1420101 were associated with high FeNO and blood eosinophil differentials, whereas minor alleles of rs17026974 and rs1921622 were associated with high blood eosinophil differentials and FeNO, respectively. Multivariate analyses revealed that the minor allele of rs1420101 additively contributed to the FeNO, blood eosinophil differentials, and reversibility of FEV1. The minor alleles of IL1RL1 SNPs were associated with high FeNO and peripheral blood eosinophilia among adult Japanese patients with stable asthma. IL1RL1 SNPs may characterize the eosinophilic phenotype with greater eosinophilic inflammation in the Japanese asthma cohort.

Prognostic value of soluble ST2 biomarker in heart failure patients with reduced ejection fraction – A multicenter study

ObjectiveTo study the prognostic value of soluble Suppression of Tumorigenicity-2 (sST2) in heart failure patients with reduced ejection fraction (HFrEF). MethodsIn this prospective, observational, multicenter study, patients with heart failure (HF) and left ventricular ejection fraction (LVEF) <50% were included. Clinical evaluation and serum levels of sST2 were estimated at five time points during follow up. Study endpoint was the relationship of baseline and serial sST2 concentration in the blood to the composite endpoints of cardiac death and re-hospitalization for worsening of HF during one year follow up period. ResultsA total of 141 patients were enrolled. The mean age was 60±10.4years. At baseline evaluation, 49.6% patients were in New York Heart Association (NYHA) class III and 36.2% in class IV. Adverse events were observed in 57 patients (40.4%); 25 (17.7%) were re-hospitalized due to worsening of HF and 32 (22.7%) died due to cardiac causes. The median value of baseline sST2 was 46.36ng/ml (IQR 31.30–78.38). sST2 concentration at baseline was significantly higher among patients with adverse events in comparison to patients without adverse events (p=<0.001). Receiver operating characteristic curve (ROC) for baseline sST2 concentration identified 49ng/ml as optimal cut-off value to predict cardiac death and re-hospitalization, with a sensitivity and specificity of 72% and 75%, respectively. ConclusionIn patients with HFrEF, sST2 concentration at baseline as well as on serial testing was significantly correlated with cardiac death and re-hospitalization for worsening of HF.

Improved early risk stratification of patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention using a combination of serum soluble ST2 and NT-proBNP.

BackgroundAlthough soluble suppression of tumorigenicity 2 (sST2) in serum is known to be associated with ischemic heart disease and heart failure, data regarding its prognostic impact in ST-segment elevation myocardial infarction (STEMI) is limited. We evaluated the prognostic impacts of serum sST2 and other serum biomarkers in STEMI patients undergoing primary percutaneous coronary intervention (PCI).MethodsConsecutive all 323 patients with STEMI that underwent primary PCI were enrolled. Blood tests and samples were obtained in an emergency room. The primary endpoint was 1-year major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of cardiovascular death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization.ResultsMean age was 59.1±13.1 years (men 84%). MACCE (20 cardiovascular deaths, 7 non-fatal MI, 4 non-fatal stroke, 7 ischemia-driven revascularizations) occurred in 38 patients (12%). After adjusting for confounding factors, Cox regression analysis revealed that high serum sST2 (>75.8 ng/mL mean value, adjusted hazard ratio 2.098, 95% CI 1.008–4.367, p = 0.048) and high serum NT-proBNP level (>400 pg/mL, adjusted hazard ratio 2.606, 95% CI 1.086–6.257, p = 0.032) at the time of presentation independently predicted MACCE within a year of primary PCI. Furthermore, when high serum sST2 level was combined with high serum NT-proBNP level, the hazard ratio of MACCE was highest (adjusted hazard ratio 7.93, 95% CI 2.97–20.38, p<0.001).ConclusionElevated serum levels of sST2 or NT-proBNP at the time of presentation were found to predict 1-year MACCE independently and elevated serum levels of sST2 plus NT-proBNP were associated with even poorer prognosis in patients with STEMI undergoing primary PCI.

Predictive value of serum sST2 in preschool wheezers for development of asthma with high FeNO.

Wheezing is common in childhood. However, current prediction models of pediatric asthma have only modest accuracy. Novel biomarkers and definition of subphenotypes may improve asthma prediction. Interleukin-1-receptor-like-1 (IL1RL1 or ST2) is a well-replicated asthma gene and associates with eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with elevated exhaled NO (FeNO), compared to the commonly used Asthma Prediction Index (API). Using logistic regression modeling, we found that serum sST2 levels in 2-3 years-old wheezers do not predict doctors' diagnosed asthma at age 6 years. Instead, sST2 predicts a subphenotype of asthma characterized by increased levels of FeNO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the predictive value of the API (AUC=0.70, 95% CI 0.56-0.84), but had also significant predictive value on its own (AUC=0.65, 95% CI 0.52-0.79). Our study indicates that sST2 in preschool wheezers has predictive value for the development of eosinophilic airway inflammation in asthmatic children at school age.

Ablation of IL-33 gene exacerbate myocardial remodeling in mice with heart failure induced by mechanical stress

Background and purposeST2 is one of the interleukin (IL)-1 receptor family members comprising of membrane-bound (ST2L) and soluble (sST2) isoforms. Clinical trials have revealed that serum sST2 levels predict outcome in patient with myocardial infarction or chronic heart failure (HF). Meanwhile, we and others have reported that ablation of ST2 caused exaggerated cardiac remodeling in both ischemic and non-ischemic HF. Here, we tested whether IL-33, the ligand for ST2, protects myocardium against HF induced by mechanical overload using ligand specific knockout (IL-33−/−) mice. Methods and resultsTransverse aortic constriction (TAC)/sham surgery were carried out in both IL-33 and WT-littermates. Echocardiographic measurements were performed at frequent interval during the study period. Heart was harvested for RNA and histological measurements. Following mechanical overload by TAC, myocardial mRNA expressions of Th1 cytokines, such as TNF-α were enhanced in IL-33−/− mice than in WT mice. After 8-weeks, IL-33−/− mice exhibited exacerbated left ventricular hypertrophy, increased chamber dilation, reduced fractional shortening, aggravated fibrosis, inflammation, and impaired survival compared with WT littermates. Accordingly, myocardial mRNA expressions of hypertrophic (c-Myc/BNP) molecular markers were also significantly enhanced in IL-33−/− mice than those in WT mice. ConclusionsWe report for the first time that ablation of IL-33 directly and significantly leads to exacerbate cardiac remodeling with impaired cardiac function and survival upon mechanical stress. These data highlight the cardioprotective role of IL-33/ST2 system in the stressed myocardium and reveal a potential therapeutic role for IL-33 in non-ischemic HF.

Serum soluble ST2 is a promising prognostic biomarker in HBV-related acute-on-chronic liver failure

The IL-33/ST2 axis is involved in the pathogenesis of many diseases such as autoimmune diseases, cancer, and heart failure. However, studies of the IL-33/ST2 pathway in HBV-related acute-on-chronic liver failure (HBV-ACLF) are lacking. The present study aimed to determine the prognostic role of serum IL-33/soluble ST2 (sST2) in HBV-ACLF. Serum levels of IL-33 and sST2 in healthy controls (HC, n=18), chronic hepatitis B (CHB, n=27) and HBV-ACLF (n=51) patients at the 1st and 4th week after enrollment were detected using ELISA, and clinical data were collected. The follow-up of HBV-ACLF patients lasted for 6 months at least. There was no significant difference of serum IL-33 level among HC, CHB and HBV-ACLF patients at week 1. However, serum sST2 level differed significantly among the three groups: highest in the HBV-ACLF group, moderate in the CHB group and lowest in the HC group. There was a reverse correlation between serum sST2 level and the survival of HBV-ACLF patients. The level of serum sST2 in HBV-ACLF survivors was significantly declined from week 1 to week 4 following the treatment, whereas that in HBV-ACLF non-survivors remained at a high level during the same period. Furthermore, serum sST2 level was significantly correlated with laboratory parameters and the most updated prognostic scores (CLIF-C OF score, CLIF-C ACLF score and ACLF grades). The receiver operating characteristics curves demonstrated that serum sST2 level was a good diagnostic marker for predicting the 6-month mortality in HBV-ACLF patients, comparable to the most updated prognostic scores. Serum sST2 cut-off points for predicting prognosis in HBV-ACLF patients were 76 ng/mL at week 1 or 53 ng/mL at week 4, respectively. HBV-ACLF patients with serum sST2 level above the cut-off point often had a worse prognosis than those below the cut-off point. Serum sST2 may act as a promising biomarker to assess severity and predict prognosis of patients with HBV-ACLF and help for the early identification and optimal treatment of HBV-ACLF patients at high risk of mortality.

IL-33 and sST2 levels in Serum of Children with Henoch-Schnlein Purpura and Their Clinical Significance

To investigate the serum IL-33 and sST2 levels in children with Henoch-Schonlein purpura (HSP), and explore their clinical significance. Total 27 HSP patients and 22 healthy controls were enrolled in present study. The expressions of IL-33 and sST2 were measured by enzyme linked immunosorbent assay (ELISA). Using real-time quantitative polymerase chain reaction (RT-PCR), the mRNA expression of IL-33 and sST2 were detected in all subjects. The level of the IL-33 in the serum of HSP group and control group was 365.5±160.6 pg/ml and 175.9±92.8 pg/ml(P< 0.05). The level of the sST2 was increased in the serum of HSP group (1788.6±523.8 pg/ml) as compared with that in control group (1083.6±489.6 pg/ml)(P>0.05), but the ratio of sST2/IL-33 in HSP patients was much lower than that in the controls(P<0.05), IL-33 and sST2 mRNA levels were up-regulated in HSP patients by 5.47±1.97-fold(P<0.05) and 3.13±2.01-fold(P<0.05) compared with controls, but sST2/IL-33 significantly decreased in HSP patients(P<0.05). The levels of IL-33 and sST2 increase in the serum of HSP patients, but the ratio of sST2/IL-33 is much lower than that in control.

Dynamic observation of IL-33 and its receptors in HIV patients who received HAART.

The purpose of this study was to observe the changes in serum IL-33 and its soluble receptors, serum sST2 level and ST2L expression in PBMCs of HIV-infected patients receiving highly-active antiretroviral therapy (HAART) for 12 monthes. Fifty-five chronic HIV-1-infected adults were recruited for this study before initiation of HAART. 30 age and gender matched healthy adults were recruited as control. Blood was obtained from each patient at baseline (0 month) and 12 months after initiation of highly active antiretroviral therapy(HAART), and each healthy person. The concentration of serum IL-33 and sST2 were detected by ELISA. plasma HIV RNA was detected by real-time fluorescent quantitative PCR. peripheral blood CD3+/CD4+ cell count, the ratio of CD4+ST2L+ positive peripheral blood mononuclear cells (PBMCs) were determined by flow cytometry. In HIV-infected patients, serum IL-33 and sST2 levels are higher and percentage of ST2L in PBMCs is lower than normal control significantly. During HAART, serum IL-33 and sST2 levels were decreased, whereas CD4+ST2L+ level was increased in PBMCs gradually. Serum IL-33 and sST2 levels positively correlated with plasma HIV RNA levels, but negatively correlated with the peripheral blood CD3+/CD4+ cell count. CD4+ST2L+ receptor in PBMC are positively correlated with the peripheral blood CD3+/CD4+ cell count, but negatively correlated with the plasma HIV viral loading. Serum IL-33 and sST2 levels, and CD4+ST2L+ expression in PBMCs are closely associated with HIV-1 infection and immune reconstitution in patients received HAART.

Increased Soluble Suppression of Tumorigenicity 2 Level Predicts All-Cause and Cardiovascular Mortality in Maintenance Hemodialysis Patients: A Prospective Cohort Study

Background: Soluble suppression of tumorigenicity 2 (sST2) is a novel cardiovascular biomarker. This study aimed to evaluate the prognostic value of sST2 in hemodialysis patients. Methods: Four hundred and fourteen maintenance hemodialysis (MHD) patients were enrolled and followed up prospectively. Serum sST2 levels were measured. The endpoint was all-cause and cardiovascular mortality. Results: During a median follow-up of 22.3 months, 58 patients died, including 31 cardiovascular deaths. sST2 was an independent predictor of all-cause mortality with a relative risk (RR) of 1.31 (95% CI 1.000-1.717, p = 0.050) and cardiovascular mortality with an RR of 2.10 (95% CI 1.507-2.927, p < 0.001). The prognostic value of sST2 was additive to N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT), as the combined use of sST2 and NT-proBNP or hs-cTnT better identified higher-risk patients. Conclusion: Elevated sST2 is an independent predictor of all-cause and cardiovascular mortality in MHD patients. A combined use of sST2 and NT-proBNP or hs-cTnT helps identify individuals of higher risk.

Do not be alarmed: understanding IL33-ST2 signalling in wound repair.

Do not be alarmed: understanding IL33-ST2 signalling in wound repair.

Can Serum ST2 Levels Be Used as a Marker of Fibrosis in Chronic Hepatitis B Infection?

Interleukin 33 (IL-33) is a cytokine belonging to the IL-1 superfamily. Soluble ST2 (sST2) binds to IL-33 and by functioning as trap receptor inhibits signal sending to Th2 via transmembrane ST2. Because Th2-type cytokines play an important role in fibrosis, the aim of this study is to determine whether sST2 can be used as a marker of fibrosis in chronic hepatitis B (CHB) patients or not.The study included 19 healthy controls, 54 patients with CHB, and 14 patients with cirrhosis because of CHB. The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the 4 factors (FIB-4) scores also calculated, and correlations between liver biopsies, sST2 levels, and these scores were analyzed in CHB and cirrhosis patients.The sST2 levels in patients with CHB were significantly higher than those in the control group subjects (median: 1133 pg/mL vs 762.5 pg/mL, respectively [P = 0.035]). In CHB patients, the METAVIR fibrosis score (stages from 0 to 4) showed a moderate correlation with serum sST2 level (r = 0.396, P = 0.004) and a weak correlation with FIB-4 score (r = 0.359, P = 0.008), but no correlation with APRI score (r = 0.253, P = 0.06). The under the curve value of serum sST2 was 0.68, and its prediction of significant fibrosis (METAVIR score ≥2) in values >674 pg/mL had a sensitivity of 91.7% and specificity of 40% (P = 0.009). According to multiple logistic regression analysis, only METAVIR fibrosis stage was found to be an independent predictor of serum sST2 elevation in CHB patients (P = 0.04).The sST2 level can be used for differentiating significant fibrosis from mild fibrosis in CHB patients. However, the efficacy of this marker should be verified by larger studies in the future.

Increased Serum Levels of the IL-33 Neutralizing sST2 in Limited Cutaneous Systemic Sclerosis.

The pathophysiology of both limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous SSc (dcSSc), representing two subtypes of an autoimmune disease of the connective tissue, is still enigmatic. Life-limiting, progressive fibrotic changes as a consequence of vasculopathy and autoimmunity are characteristic in varying extent for lcSSc and dcSSc. Previously, an increased IL-33 serum concentration in early phase SSc patients and an elevated tissue expression of its receptor, ST2L, on endothelial cells (EC) were described. While suggested as a biomarker for fibrotic diseases, for example liver fibrosis, the role of soluble ST2 (sST2) in the pathological processes and its contribution to vascular fibrosis in SSc has not been investigated. Here, we showed that sST2 is elevated in late phase limited cutaneous SSc (lcSSc) as compared to patients with shorter disease duration or with the diffuse subtype of SSc. We demonstrated that sST2, not IL-33, is significantly increased in serum of lcSSc patients with disease duration over 9years. Soluble ST2 was not elevated in healthy controls or in SSc patients with early skin involvement or disease duration shorter than 9years. Furthermore, we observed that sST2 serum levels were lowered by iloprost (prostacyclin) treatment. After 5days of iloprost infusion, sST2 serum levels fell in 6 of 7 patients. Therefore, we not only like to propose sST2 as a biomarker for progressive vascular fibrosis, but moreover, suggest that the involvement of sST2 in the pathogenesis of lcSSc may be exploited therapeutically.

Soluble ST2 and myocardial fibrosis in 3T cardiac magnetic resonance

>Objective. The soluble form of ST2 (sST2) is a novel laboratory parameter for cardiac risk prediction, and over the past years, several studies have tried to evaluate its utility, especially in the management of heart failure. We investigated whether increased serum levels of sST2 show a characteristic pathomorphologic pattern in 3-Tesla cardiac magnetic resonance imaging (CMRI). Methods. One hundred and fifty-six patients referred to 3T CMRI due to suspected coronary artery disease (CAD) or myocarditis were prospectively enrolled in the study. Ninety patients were diagnosed with CAD, 22 patients with myocarditis, and 44 patients, who constituted the reference group, showed no pathologic CMRI pattern. Results. There was no significant difference between the sST2 values for patients in the reference group and patients with CAD or myocarditis. The sST2 concentration showed a weak correlation with the NYHA functional class (P = 0.002, r = 0.22), but correlation of sST2 and LGE, left ventricular parameters, and LVEF could not be seen. In contrast NT-proBNP was positively correlated to left ventricular parameters, LGE, and NYHA class function (P < 0.05). Additionally, it showed an inverse relationship to LVEF (P < 0.001, r = − 0.42). Conclusions. Soluble ST2 is not able to detect myocardial scar and should not be used alone as a parameter for detection of inflammation and myocardial scar formation.

Status of soluble ST2 levels in serum of HTLV-1 infected individuals.

ST2 is a member of IL-1 receptor family expressed on Th2 cells and regulates Th2 responces. The gene of ST2 encodes soluble ST2 (sST2) and the transmembrane ST2 (ST2L) isoforms through alternative mRNA splicing. The discovery of IL33/ ST2 signaling pathway, has drawn a great scientific attention to this system. sST2 has been shown to be an indacating factor in various infl ammatory conditions. This study aims to evaluate serum sST2 levels in HTLV-1 infected patients. This study included 49 HTLV-1 seropositive cases of which 14 were sympthomatic. Controls consisted of 30 healthy volunteers. sST2 level was measured using a quantitative ELISA assay and the results of the study groups were compared. Corroborating the previous reports, sST2 was lower in females (P = 0.003). The sST2 levels was slightly increased in HTLV-1 patients, though such increase was not statistically significant (P = 0.91), in addition sST2 level did not correlate significantly to the disease duration (P = 0.78). Despite some other chronic viral infection, HTLV-1 seems not to induce high serum sST2. However owing to relatively high normal variation of sST2 levels and rather small sample size, we stongly recommend further reseach with preferably larger sample size to evalute sST2 in HTLV-1 infected patients.