Serum sST2 Levels Research Articles

Prognostic role of serum soluble ST2 of advanced breast cancer patients: a retrospective cohort study.

The soluble suppression of tumorigenicity 2 receptor (sST2) binds to interleukin-33 (IL-33) and blocks IL-33 and ST2 binding, suggesting that sST2 acts as a "decoy" receptor for IL-33 and is involved in the malignant progression of breast cancer. This paper aimed to investigate the differences in sST2 expression in patients with different molecular subtypes of breast cancer and assess its clinical value in the prognostic evaluation of advanced breast cancer. In this paper, we collected sera from 91 patients firstly diagnosed with advanced breast cancer at the Tianjin Medical University Cancer Institute and Hospital from 2008 to 2021 during their first hospitalization. We detected the expression level of sST2 in the serum of patients with different molecular fractions of breast cancer and analyzed the relationship between serum sST2 levels and breast cancer-related bone metastasis, cardiotoxicity, and overall survival. Bone metastases were detected using the Emission Computed Tomography technique, and chemotherapy drug-induced cardiotoxicity was detected by echocardiography. The Overall Survival was evaluated using the Kaplan-Meier estimator, and multivariate Cox regression analysis was performed to demonstrate the association between variables and sST2 levels. Serum sST2 levels did not vary among the different pathological types, molecular types, and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor proliferation marker (Ki-67) subgroups, and only differed significantly in the cardiotoxicity group. There were no statistical differences in tissue polypeptide specific antigen (TPSA), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153), D-dimer, and inflammatory indexes neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) among different molecular subgroups. However, except for triple-negative breast cancer (TNBC), there was no difference in peripheral blood soluble ST2 concentrations among other molecular subtypes. Meanwhile, the survival of the high sST2 level group among advanced breast cancer patients was significantly lower than that of the normal group, and sST2 expression was closely related to cardiotoxicity and clinical stage. Serum sST2 is not only traditionally applied to the assessment of cardiac injury, but can also be utilized for assessing the prognosis of advanced breast cancer, excluding the influence of clinical stage and cardiotoxicity.

Interleukin-33/sST2: Dynamic assessment in patients with acute coronary syndrome

PurposeInterleukin (IL)-33 and its soluble receptor ST2 (sST2) play a crucial role in the immune response. sST2 has been approved by the Food and Drug Administration as a prognostic biomarker of mortality in chronic heart failure patients, however, the role of IL-33 and sST2 in atherosclerotic cardiovascular disease remains unclear. The aim of this study was to measure serum level of IL-33 and sST2 of patients at the onset of acute coronary syndrome (ACS) and 3 months after primary percutaneous revascularization. Patients and methodsForty patients were divided into ST segment elevation myocardial infarction (STEMI) group, non-ST segment elevation myocardial infarction (NSTEMI) and unstable angina (UA) group. IL-33 and sST2 level were measured with ELISA. Additionally, IL-33 expression in peripheral blood mononuclear cells (PBMCs), was evaluated. ResultsAll ACS patients had a significantly lower level of sST2 3 months after ACS as compared to the baseline (p ​< ​0.039). The STEMI patients had higher serum levels of IL-33 at the moment of ACS as compared to 3 months after the event, with an average decrease of 17.87 ​pg/ml (p ​< ​0.007). Conversely, sST2 serum levels were still high after 3 months following an ACS in STEMI patients. ROC curve demonstrated that increased IL-33 serum level could be STEMI predictor. ConclusionsThe assessment of the baseline and dynamics of changes in IL-33 and sST2 concentrations in patients with ACS may be important for the diagnostic process and may help in understanding of how the immune mechanisms work at the moment of an ACS event.

The diagnostic value of sST2 for myocardial fibrosis in idiopathic inflammatory myopathies in subclinical stage of cardiac involvement.

Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM. A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed. IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s.d. 30.4)] vs 14.4 (5.5), P < 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P = 0.000), ECV (r = 0.371, P = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P = 0.024) by Spearman's correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P < 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P < 0.01), respectively. sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM.

Interleukin-33 and Soluble ST2 Levels in Infants with Hypoxic-Ischemic Encephalopathy

Introduction: Interleukin (IL)-33 and its receptor ST2L play key roles in the IL-33/ST2 signaling pathway. Soluble ST2 (sST2) inhibits the proper function of IL-33. sST2 levels are increased in patients with several neurological diseases, but in infants with hypoxic-ischemic encephalopathy (HIE), IL-33 and sST2 levels have not been studied. This study aimed to investigate whether serum levels of IL-33 and sST2 are useful as biomarkers of HIE severity and prognostic factors for infants with HIE. Methods: Twenty-three infants with HIE and 16 controls (gestational age ≥36 weeks and ≥1,800 g birth weight) were enrolled in this study. Serum levels of IL-33 and sST2 were measured at <6 h, 1–2, 3, and 7 days of age. Hydrogen-1 magnetic resonance spectroscopy was performed, and ratios of peak integrals of lactate/N-acetylaspartate (Lac/NAA) were calculated as objective indicators of brain damage. Results: In the moderate and severe HIE, serum sST2 concentrations were increased and there was a good correlation between serum sST2 and HIE severity on days 1–2, whereas no variation was observed in serum IL-33. Serum sST2 levels were positively correlated with Lac/NAA ratios (Kendall’s rank correlation coefficient = 0.527, p = 0.024), and both sST2 and Lac/NAA ratios were significantly higher in HIE infants with neurological impairment (p = 0.020 and <0.001, respectively). Conclusions: sST2 may be a useful predictor of severity and later neurological outcomes in infants with HIE. Further investigation is required to elucidate the relationship between the IL-33/ST2 axis and HIE.

Los niveles de ST2 soluble están relacionados con la fibrosis miocárdica de sustitución en la estenosis aórtica grave

Introduction and objectivesPatients with aortic stenosis (AS) exhibit left ventricular (LV) remodeling and replacement myocardial fibrosis (RMF). Whether sST2 is associated with RMF measured by cardiac magnetic resonance and with sex remains unknown. MethodsWe recruited 79 consecutive patients (73.0 [68.0-78.0] years; 61% men) with severe isolated AS underdoing valve replacement. RMF was identified and quantified by late gadolinium enhancement (LGE). Serum sST2 levels were determined. ResultsRMF was associated with higher circulating sST2 levels, LV hypertrophy and dilation, and lower LV ejection fraction. All patients with LV dysfunction had RMF. Circulating levels of sST2 ≥ 28.8 ng/mL were associated with RMF and greater LV hypertrophy. LGE mass was correlated with LV remodeling and sST2. Of note, sST2 levels were also associated with the RMF pattern, being higher in midwall than in subendocardial fibrosis. Multivariate analyses showed that only LV ejection fraction and sST2 levels were associated with RMF. Moreover, men had higher levels of sST2 and RMF. RMF was associated with higher LV dilation and hypertrophy only in men and was correlated with LGE mass. ConclusionsSST2 was an independent factor for RMF in patients with severe isolated AS. The presence of RMF was predicted by sST2 ≥ 28.2 ng/mL, and was associated with greater LV hypertrophy. sST2 expression and clinical associations may be sex-specific.

Heart failure with preserved ejection fraction: the role of microvascular dysfunction

Aim. To evaluate the relationship between coronary microvascular dysfunction (CMD), biomarkers of cardiac fibrosis and cardiac remodeling (soluble ST2 (sST2), fibroblast growth factor-23 (FGF-23), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and NT-proBNP), parameters of diastolic dysfunction (DD), and the presence of heart failure with preserved ejection fraction (HFpEF) in symptomatic patients.Materials and methods. Study participants were 59 patients with non-obstructive coronary artery disease (CAD) and preserved left ventricular ejection fraction (LVEF) of 62 (56; 67) %. Non-obstructive CAD was verified by coronary computed tomography angiography. Stress-and rest-myocardial blood flow (MBF) and coronary flow reserve (CFR) parameters were evaluated by CZT SPECT. Serum levels of cardiac biomarkers were measured by the enzyme immunoassay. Two-dimensional transthoracic echocardiography was used to assess DD parameters.Results. Decreased CFR was defined as CFR ≤ 2. Therefore, CMD was defined as the presence of decreased CFR in the absence of flow-limiting CAD. Distribution of patients was performed by CFR values: group 1 included patients with preserved CFR (&gt;2, n = 35), and group 2 encompassed patients with decreased CFR (≤2, n = 24). In 87.5% of cases, patients with CMD were diagnosed with HFpEF, whereas in patients with preserved CFR, heart failure was diagnosed only in 51.4% of cases (p &lt; 0.0001). CFR values were correlated with the left atrial volume (r = –0.527; p = 0.001), E / A ratio (r = –0.321, p = 0.012), and E / e’ (r = –0.307; p = 0.021). Following the ROC analysis, the levels of sST2 ≥ 31.304 ng / ml (AUС = 0.730; р = 0.004) and NT-proBNP ≥ 0.034 pg / ml (AUС = 0.815; р = 0.034) were identified as cut-off values for the presence of CMD in patients with non-obstructive CAD.Conclusion. The obtained data suggest that CMD may play an essential role in HFpEF. The values of CFR were correlated with DD parameters, and decreased CFR was associated with overexpression of biomarkers of cardiac fibrosis and cardiac remodeling. Serum levels of sST2 and NT-proBNP were identified as cut-off values for the presence of CMD in patients with non-obstructive CAD.

Biomarkers for Predicting the Occurrence and Progression of Atrial Fibrillation: Soluble Suppression of Tumorigenicity 2 Protein and Tissue Inhibitor of Matrix Metalloproteinase-1.

Soluble suppression of tumorigenicity 2 protein (sST2) and tissue inhibitor of matrix metalloproteinase (TIMP)-1 are involved in multiple pathogenic pathways, including cardiac remodeling, which is the main pathology of atrial fibrillation (AF). This study aims to investigate the previously unexplored relationship between the serum levels of sST2, TIMP-1, and AF. This was a prospective cross-sectional study conducted at the Capital Medical University Affiliated Beijing Anzhen Hospital between June 2019 and July 2020, with a total of 359 participants. The clinical characteristics and laboratory results of the patients were compared, and multivariable ordinal logistic regression was used to evaluate the relationship between serum sST2, TIMP-1, and AF. The participants included 110 patients with sinus rhythm (SR), 113 with paroxysmal AF (the paroxysmal AF group), and 136 with persistent AF (the persistent AF group). It was found that the sST2 levels gradually increased in these three groups, from 9.1 (6.7-12.4 pg/ml) in the SR group to 14.0 (10.4-20.8 pg/ml) in the paroxysmal AF group and to 19.0 (13.1-27.8) pg/ml) in the persistent AF group (p < 0.001). The multivariable ordinal logistic regression model for sST2 and TIMP-1 demonstrated that sST2 had an area under the receiver operating characteristic (ROC) curve (AUC) of 0.797 (95% confidence interval (CI) 0.749-0.846, p < 0.001) and TIMP-1 had an AUC of 0.795 (95% CI 0.750-0.841, p=0.000). The multivariable ordinal logistic regression model for sST2 and TIMP-1 showed good discrimination between SR and AF, with an AUC of 0.846, and the addition of clinical factors, such as brain natriuretic peptide (BNP), left atrial diameter, age, and gender, to the biomarker model improved the detection of SR and AF (AUC 0.901). In this cohort study, sST2 and TIMP-1 were associated with AF progression, independent of clinical characteristics and biomarkers. Soluble ST2 and TIMP-1 combined with age, elevated N-terminal-pro hormone BNP(NT-BNP), and an enlarged left atrium were able to demonstrate the progression of AF reliably.

Soluble ST2 levels are related to replacement myocardial fibrosis in severe aortic stenosis

Introduction and objectivesPatients with aortic stenosis (AS) exhibit left ventricular (LV) remodeling and replacement myocardial fibrosis (RMF). Whether sST2 is associated with RMF measured by cardiac magnetic resonance and with sex remains unknown. MethodsWe recruited 79 consecutive patients (73.0 [68.0-78.0] years; 61% men) with severe isolated AS underdoing valve replacement. RMF was identified and quantified by late gadolinium enhancement (LGE). Serum sST2 levels were determined. ResultsRMF was associated with higher circulating sST2 levels, LV hypertrophy and dilation, and lower LV ejection fraction. All patients with LV dysfunction had RMF. Circulating levels of sST2 ≥ 28.8 ng/mL were associated with RMF and greater LV hypertrophy. LGE mass was correlated with LV remodeling and sST2. Of note, sST2 levels were also associated with the RMF pattern, being higher in midwall than in subendocardial fibrosis. Multivariate analyses showed that only LV ejection fraction and sST2 levels were associated with RMF. Moreover, men had higher levels of sST2 and RMF. RMF was associated with higher LV dilation and hypertrophy only in men and was correlated with LGE mass. ConclusionsSST2 was an independent factor for RMF in patients with severe isolated AS. The presence of RMF was predicted by sST2 ≥ 28.2 ng/mL, and was associated with greater LV hypertrophy. sST2 expression and clinical associations may be sex-specific.

729 BIOMARKERS FOR EARLY DIAGNOSIS OF CARDIAC INVOLVEMENT IN SYSTEMIC SCLEROSIS

Abstract Introduction Systemic Sclerosis (SSc) is an autoimmune disease characterized by microvascular damage, immune system dysregulation and fibrosis of skin and internal organs. It is reported that asymptomatic involvement of the heart was found in 70% of SSc patients. The role of biomarkers in the early detection of fibrosis and vascular damage in SSc is not yet completely defined. Serum levels of sST2, Galectin 3, ANP, IL6 are a potential marker of cardiac involvement. In patients with chronic heart failure elevated levels of galectin-3 (&amp;gt;17.8 ng/ml) are a marker of worse prognosis. Moreover, a previous study reported a possible role of galectin-3 as an independent predictor of all-cause and cardiovascular mortality in SSc. Material and Methods We enrolled 62 SSc patients (53 females, median age 52 years) who fulfilled inclusion criteria. 35 patients had limited cutaneous SSc and 27 diffuse cutaneous SSc. 30 Healthy Controls (HC) were also enrolled [20 females; median age 50 years]. All SSc patients had normal echocardiographic and cardiac MRI findings. Results In SSc patients, the median Galectin value was 16.7 ng/ml, significantly higher than HC median (10,7 ng/Ml). sST2 and IL-6 median value was 30 ng/mL and 12,3 pg/mL respectively, which resulted significantly higher than the median value of HC patient (21,55 ng/mL and 4,5 pg/mL respectively). Therefore, there was a significant difference in biomarkers levels in the SSc group compared with controls. Conclusion These data suggest that these biomarkers can help identify a subgroup of SSc patients, with normal echocardiographic and RMN findings, who are at risk of developing heart involvement. In fact, all patients are scheduled for yearly echocardiographic re-evaluation as ESC guidelines recommend for earlier detection of pulmonary arterial hypertension (PAH), a leading cause of death in systemic sclerosis (SSc).

Peri-implant crevicular fluid and serum levels of soluble ST2 in peri-implant diseases: A pilot study.

Soluble ST2 (sST2) is a current biomarker of cardiovascular disease. It is used to predict susceptibility to cardiovascular diseases and to analyze their prognosis. Serum sST2 level increases in inflammatory diseases such as periodontitis. However, the level of sST2 in peri-implant diseases and crevicular fluid has not been investigated yet. Thus, the aim of this cross-sectional study is to analyze the level of sST2 in peri-implant health and diseases. Sixty-nine participants were divided into 3 groups as peri-implant health (PH), peri-implant mucositis (PM), and peri-implantitis (P-I). Peri-implant crevicular fluid (PICF) and serum samples were collected from each participant. The levels of sST2 and IL-6 in PICF and sST2, IL-6, and CRP in serum were compared between the groups. Pocket depth (PD), modified bleeding index (mBI), modified plaque index (mPI), keratinized mucosa index (KTW), and gingival/mucosal recession (REC) were recorded as clinical parameters. Biomarkers in the serum and PICF were analyzed by ELISA kit. Sixty-nine patients were included in the study. The differences in the following parameters were statistically significant between groups: age (p=.009), implant function time (p=.027), PD (p < .001), mBI (p < .001), mPI (p < .001), and KTW (p=.043). The PICF volume of P-I and PM groups were statistically higher than PH (p < .001). The amount of sST2 in P-I and PM groups were higher than PH (p=.043). Serum CRP was higher in the P-I group than in other groups (p=.034). There were no significant differences in serum sST2 (p=.247) and IL-6 (p=.110) levels between groups. The PICF levels of sST2 were significantly higher in PM and P-I groups compared to the healthy group. However, no significant difference was observed between the groups in terms of serum sST2 level.

Abstract 9361: Interleukin-33 System as Potential Biomarker and Therapeutic Target in Kawasaki Disease

Introduction: Kawasaki disease (KD) is an acute, self-limiting, febrile systemic vasculitis of unknown cause associated with the development of coronary artery lesions (CALs) during childhood. Damage-associated molecular patterns (DAMPs) from cell death and oxidative stress have been shown to be involved in the development of KD vasculitis. Interleukin (IL)-33 is released from damaged endothelial cells and acts as DAMPs. Hypothesis: IL-33 and its receptor (ST2) might be involved in KD pathogenesis. Methods: Serum levels of soluble ST2 (sST2) in KD patients were measured before their first therapy. Furthermore, we investigated the impact of IL-33 on human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs). Results: Serum levels of sST2 were significantly higher in KD patients with CALs than in those with normal coronary arteries (87.2 [18.4-224.0] ng/mL vs. 31.7 [8,8-290.3] ng/mL, p = 0.017). In vitro , IL-33 upregulated the expression of ST2L and increased production of sST2, IL-6, IL-8, and monocyte chemoattractant protein–1 in HCAECs in a time- and concentration-dependent manner. Notably, compared to isoconcentration of tumor necrosis factor-α (TNF-α), IL-33 significantly increased IL-6 production; 10 ng/mL of IL-33 increased the production of IL-6 by 13-fold compared with that by TNF-α (9.1 ng/mL vs. 0.7 ng/mL, p &lt; 0.05). Moreover, IL-1β increases IL-33 production by HCASMCs in a concentration-dependent manner. Conclusions: The results of the present study suggest that the IL-33/ST2 axis might be involved in the development of KD vasculitis. The IL-33/ST2 axis may be a therapeutic target for the treatment of KD.

Interleukin-33/ST2 Axis as Potential Biomarker and Therapeutic Target in Kawasaki Disease.

Kawasaki disease (KD) is an acute, self-limiting, febrile systemic vasculitis of unknown cause associated with the development of coronary artery lesions (CALs) during childhood. Damage-associated molecular patterns (DAMPs) from cell death and oxidative stress have been shown to be involved in the development of KD vasculitis. Interleukin (IL)-33 is released from damaged endothelial cells and acts as a DAMP. We studied whether IL-33 and its receptor (ST2) might be involved in KD pathogenesis. Serum levels of soluble ST2 (sST2) in KD patients were measured before their first therapy. Furthermore, we investigated the impact of IL-33 on human coronary artery endothelial cells (HCAECs). Serum levels of sST2 were significantly higher in KD patients with CALs than in those with normal coronary arteries. In vitro, IL-33 upregulated the expression of ST2L and increased production of sST2, IL-6, IL-8, and monocyte chemoattractant protein-1 in HCAECs in a time- and concentration-dependent manner. Moreover, IL-33 induced significantly greater production of IL-6 and IL-8 in HCAECs compared to the condition stimulated with isoconcentration of tumor necrosis factor-α. The results of the present study suggest that the IL-33/ST2 axis might be involved in the development of KD vasculitis. The IL-33/ST2 axis may be a therapeutic target for the treatment of KD.

Dynamic right ventricular structural and functional changes in acute decompensated heart failure, new insights from serum sST2 and speckle-tracking echocardiography imaging

Abstract Background Right ventricular (RV) mechanics are affected by volume/pressure overload in acute decompensated heart failure (ADHF) which can be detected using biomarkers and echocardiography. ST2 (suppression of tumorigenicity 2) is a biomarker of myocardial fibrosis and remodeling, that has been studied in patients with ADHF. Although baseline serum soluble ST2 (sST2) values at ADHF admission have been proved to predict outcomes, serial measurements are even of greater value. Purpose To evaluate the right ventricular dynamic structural and functional changes in ADHF patients during hospitalization, using serum sST2 and speckle-tracking echocardiography imaging. Methods We prospectively enrolled 61 ADHF patients with LV ejection fraction less than 50% and serum NT-proBNP more than 900 pg/ml. All patients received intravenous diuretics and did not require inotropic support during hospital stay. Blood samples were collected to measure serum sST2 levels on hospital admission and discharge. All patients underwent serial conventional and speckle tracking echocardiography on admission, at 48 hours and on hospital discharge. RV speckle tracking echocardiography analysis was done using 2D Cardiac Performance Analysis version 4.6. Results Serum sST2 had significant strong positive correlation with serum NT-proBNP on admission (r=0.84, P&amp;lt;0.0001) and showed significant reduction from 2.47 (1.27–4.05) ng/ml on admission to 1.86 (1.06–3.24) ng/dl at hospital discharge (P&amp;lt;0.0001) denoting successful decongestion. There was significant decrease in inferior vena cava diameter (P&amp;lt;0.0001) and estimated pulmonary artery systolic pressure (EPASP) (P=0.002) throughout hospital stay, however this was not associated with significant change in RV dimensions (P&amp;gt;0.05) or contractility assessed by trans-annular plane systolic excursion (TAPSE) (P=0.09) and S-wave velocity at lateral tricuspid annulus (P=0.9). There was significant improvement in RV free wall strain (RVFWS) (P=0.005) assessed by speckle tracking echocardiography which was mainly noticed after the first 48 hours till discharge, but RV 4-chamber strain (RV4CS) did not change significantly (P=0.06). Conclusions RVFWS assessed by speckle tracking echocardiography can detect improvement in RV systolic function not detected by other conventional echocardiographic parameters in ADHF patients. Improvement in RVFWS together with decline in serum sST2 levels can be used as marker of improved cardiac mechanics and successful decongestion. Funding Acknowledgement Type of funding sources: None.

The correlation between maternal serum sST2, IL‐33 and NT‐proBNP concentrations and occurrence of pre‐eclampsia in twin pregnancies: A longitudinal study

The primary objective of this study was to determine the longitudinal profile of serum sST2 (soluble suppression of tumorigenicity 2), IL-33 (interleukin-33) and NT-proBNP (N-terminal pro-brain natriuretic peptide) concentrations in twin pregnancies with pre-eclampsia (PE) and those normotensive twins. The secondary objective was to test whether the change of serum sST2,IL-33 and NT-proBNP is related to PE in twin pregnancies. This is a longitudinal nested case-control study and all 156 dichorionic (DC) pregnancies were from a prospective cohort of twin pregnancies who received antenatal care and gave two live births at Peking University Third Hospital between October 2017 and September 2020. Four to five milliliters of peripheral blood of each pregnant woman were collected during the following three intervals: (1) 6-11+6 weeks; (2) 24-27+6 weeks; (3) 28-31+6 weeks. We found that sST2 and NT-proBNP levels increased as pregnancy progressed in normotensive twin pregnancies and further increased in PE group, while no differences were found in IL-33 levels throughout pregnancy. Then the correlation of biomarker levels with the occurrence of PE was assessed. Our results indicated that combining maternal serum sST2 and NT-proBNP levels yielded the highest predictive value on the occurrence of PE significantly higher than the predictive value of any markers alone. Interestingly, the predictive value of second trimester (AUC=0.876, 95%CI 0.824-0.928, LR-0.338, LR+7.67, p<0.001)was higher than that of early-third trimester (AUC=0.832, 95%CI 0.769-0.896, LR-0.29, LR+3.845, p<0.001). Serum sST2 and NT-proBNP concentrations during second and early-third trimester were associated with the occurrence of PE in twin pregnancies.

Serum-soluble ST2 and systemic sclerosis arthropathy.

Interleukin (IL)33 and its receptor ST2 have been involved in the pathogenesis of several conditions, including arthritis. The aim of the study was to evaluate the association between IL33 or soluble ST2 (sST2) serum levels and systemic sclerosis (SSc) articular involvement. IL33 and sST2 serum levels were measured in 64 SSc patients and 24 HC matched for sex and age. Articular involvement assessed by using Disease Activity Score 28 based on erythrocyte sedimentation rate (DAS28-ESR), presence of tendon friction rubs (TFRs) and finger-to-palm (FTP) distance. sST2 serum levels were significantly higher in SSc patients with DAS28-ESR > 3.2 than in SSc patients with DAS28-ESR⩽3.2 [9726.1 (IQR 7746.5 - 14,953.5) pg/mL vs 7611.7 (IQR 5162.6 -11,036.7) pg/mL; p < 0.05]. sST2 serum levels were significantly higher in SSc patients with TFRs compared to SSc patients without TFRs [9726.1 (IQR 7746.5 - 14,953.5) pg/mL vs 7426.4 (IQR 5145.9 - 10,593.5) pg/mL; p < 0.01] and in SSc patients with FTP ≥ 1cm compared to SSc patients with FTP < 1cm [9683.7 (IQR 8067.2 - 16,387.6) pg/mL vs 7679.1 (IQR 5246.1 - 11,472.2) pg/mL; p < 0.05]. No significant association was observed between IL33 and DAS28-ESR, TFRs and FTP. A slightly positive linear correlation was found between sST2 and Disease Activity Index (r = 0.294, p < 0.05) and Disease Severity Scale (r = 0.265, p < 0.05). sST2 serum levels were positively correlated with DAS28-ESR (r = 0.371, p < 0.01). Elevated sST2 serum levels were associated with higher articular disease activity, TFRs and hand dysfunction, suggesting that sST2 might have a role in the pathogenesis of SSc articular involvement. Key Points • In SSc patients elevated serum levels of sST2 were associated with higher articular disease activity • High serum levels of sST2 were reported in SSc patients with TFRs and hand dysfunction • sST2 might have a role in the pathogenesis of SSc articular involvement.

Interleukin-33 and soluble suppression of tumorigenicity 2 in scleroderma cardiac involvement

Interleukin (IL)-33 is part of the IL-1 family of cytokines and soluble suppression of tumorigenicity 2 (sST2) is part of the family of IL-1 receptors. In systemic sclerosis (SSc), IL-33 and sST2 are involved in cardiac manifestations such as diastolic dysfunction (DD), autonomic dysfunction (AD) and right ventricular–pulmonary arterial coupling assessed by tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP). Serum levels of IL33 and sST2 were assessed in 50 SSc patients and 14 healthy controls (HC). Clinical assessment, echocardiography and heart rate variability (HRV) analysis were performed in SSc patients. Serum levels of IL-33 and sST2 were significantly higher in SSc patients than HC. A linear positive correlation between modified Rodnan skin score and IL33 was observed. Serum values of sST2 were higher in SSc patients with DD than in patients without DD [15403 pg/ml (12,208–19,941) vs 8556 pg/ml (6820–11,036), p < 0.001]. sST2 showed a negative correlation with standard deviation of normal-to-normal RR intervals (SDNN) (r = − 0.281, p < 0.05) and positive correlation with low frequency/high frequency (LF/HF) (r = 0,349, p < 0.01). Negative linear correlation exists between sST2 and TAPSE/sPAP (r = − 0.398, p < 0.01). Serum levels of IL-33 and sST2 are higher in SSc patients than HC. Serum levels of sST2 are a potential marker of DD, AD and right ventricular–pulmonary arterial coupling.

Soluble ST2 and nutritional status in patients hospitalized with heart failure with reduced ejection fraction - pilot study

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Student Scientific Society Background Chronic heart failure with reduced ejection fraction (HFrEF) is very often accompanied by malnutrition, which seems to be a marker for poor prognosis. With still high prevalence of HFrEF new aspects of malnourishment should be assessed in order to plan a more individualized management and to achieve better prognosis. In addition to that the multimarker approach to evaluating HFrEF is gaining importance. One of the most promising new markers seems to be the soluble receptor for interleukin-33 (IL-33) - sST2 peptide. Purpose The aim of the study was to find relationship between serum sST2 level and malnourishment indicators in patients with HFrEF. Methods 33 consecutive patients hospitalized in the Department of Cardiology. The sST2 level was assessed using the rapid ST2 test. We assessed nutritional status with the Mini Nutritional Assessment (MNA) questionnaire and collected the chosen clinical and biochemical parameters related to nutrition. It was tested if sST2 level could predict risk of malnutrition defined as MNA score below or equal to 23.5 using ROC curve analysis. Then to further evaluate the relation between nutritional status and sST2 level appropriate correlations were tested. Results The studied group consisted of 9.1% women, mean age was 55.3 ± 10.0 years, left ventricular ejection fraction - 24.8 ± 8.7%, sST2 level - 49.84 ± 37.02 ng/ml. Using ROC curve analysis we found that sST2 levels can predict the risk of malnutrition with both considerable sensitivity – 0.786, specificity – 0.737 and an area under the curve (AUC) 0.726 (95%CI 0.548-0.903; p=0.013). The optimal cutoff point - 35 ng/ml was derived and according to this value patients were divided into two groups. MNA score was 22.4 ± 2.3 in group with high ST2 (&amp;gt;35 ng/ml) and 24.4 ± 2.4 in group with low ST2 (&amp;lt;35 ng/ml); the difference was statistically significant (p=0.026). Using Spearman’s Rank-Order Correlation we found that sST2 level correlated significantly with total protein level (p=0.0349, R=-0.46), albumin level (p&amp;lt;0.001, R=-0.80) and total cholesterol level (p=0.002, R=-0.52), while no relevant relation to BMI nor triglycerides was found. Conclusions The study revealed a potential value of sST2 level in predicting impaired nutritional status defined with MNA and its correlation with serum protein, albumin and total cholesterol. More research needs to be conducted in order to verify these relations and to study its usefulness.

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.

Soluble ST2 in serum predicts the prognosis of idiopathic pulmonary fibrosis: a retrospective study.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a heterogeneous and progressive fibrosing interstitial lung disease with a poor prognosis. However, there are currently no effective biomarker that can reliably predict the prognosis for IPF in clinic. The serum level of soluble suppression of tumorigenicity-2 (sST2), which is involved in the immune response, has proven to be a prognostic predictor for various diseases. Previous studies have confirmed that the immune dysfunction plays an important role in the pathogenesis of IPF and the serum sST2 concentrations in patients with IPF are elevated. However, the relationship between sST2 and the prognosis of IPF remains unknown.MethodsA total of 83 patients with IPF and 20 healthy controls from 2016 to 2021 were enrolled and demographic variables, indices of lung function testing as well as the biomarkers including the sST2 were obtained at baseline. During follow-up, the primary endpoint was defined as all-cause death and clinical deterioration. Cox hazard models and Kaplan-Meier method were used to assess the prognostic value of various indices including sST2.ResultsMean duration of follow-up was 29 months, during which 49 patients had an event, and of them, 35 patients died. The sST2 level was higher in the IPF patients compared with the healthy controls. Although the sST2 level did not directly predict all-cause death in the present study, it was proved to be an independent predictor of event-free survival. Multivariate forward stepwise model which was adjusted by age, sex, and body surface area (BSA) showed that the overexpression of sST2 increased the hazard ratio [1.005, 95% confidence interval (CI): 1.001–1.010]. A higher sST2 serum level heralded more deterioration and the poor outcomes. Moreover, the effect of sST2 on the prognosis of IPF may not necessarily involve the development of IPF-related pulmonary hypertension (PH).ConclusionsIn our study, the sST2 serum level was significantly elevated and a higher serum level of sST2 predicted more deterioration and poor outcomes in patients with IPF. Thus, sST2 can serve as a valuable prognostic biomarker for the outcome of IPF. However, further multicenter clinical trials of larger sample size are needed in the future.

SST2 Level at Decompensated Chronic Heart Failure in Patients with Dilated Cardiomyopathy

The purpose of the study was to evaluate the relationship between clinical and functional changes and sST2 levels in patients with dilated cardiomyopathy (DCM) admitted to the hospital due to decompensated chronic heart failure (CHF). Methods and Results: The study involved 64 DCM patients with clinical signs of decompensated CHF. According to the sST2 level, the patients were divided into two groups. Group 1 included 30 patients with sST2 level &lt;35ng/ml; Group 2 included 34 patients with sST2 level ≥35ng/ml. All patients underwent the following examinations: collection of anamnestic data, physical examination, general clinical and laboratory blood tests, 12-lead ECG, conventional 2D echocardiography in M- and B-modes, the 6MWT, and the assessment of the quality of life according to the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The serum level of sST2 was determined by enzyme immunoassay using the Presage ST2 Assay. The duration of CHF was significantly longer in Group 2 than in Group 1(48.7±6.5 mth versus 29.6±7 mth P&lt;0.05), and the number of hospitalizations per year was more frequent. Group 2 patients were characterized by lower blood pressure levels and high heart rate (P&lt;0.05). At the same time, the 6MWT value was lower and MLHFQ score was higher in Group 2 than in Group 1 (P&lt;0.001 in both cases). In Group 1, LVEF was significantly higher and LVM was significantly lower than in Group 2 (P&lt;0.001). All in all, Group 2 patients had more pronounced disorders in LV systolic dysfunction. The correlation analysis revealed an inverse correlation between the sST2 level and 6MWT (r=-0.69, P&lt;0.01), as well as LVEF (r=-0.26, P&lt;0.01). Statistically significant direct correlations were found between the sST2evel and the size and volume of the LV cavities. Conclusion: sST2 is a clinically relevant biomarker that reflects pathophysiological processes and provides prognostic information in the setting of DCM, especially in patients with HF.