Serum sST2 Levels Research Articles

Blood biomarkers to detect functional impairment in adult patients with repaired Tetralogy of Fallot

Abstract Background The relationship between plasma brain natriuretic peptide (NT-proBNP) and soluble suppression of tumorigenicity-2 (sST2) with structural adaptions and exercise capacity remains incompletely described in patients with repaired Tetralogy of Fallot (rTOF). Methods Peripheral venous blood samples were drawn for 99 patients with repaired TOF, 59 patients with severe pulmonary regurgitation (PR) and 40 patients with no or mild PR. NT-proBNP was measured using enzyme-linked immunosorbent assays (Roche Diagnostics, Indianapolis, IN). Soluble ST2 levels were assessed on Aspect-plus ST2 quantitative rapid test. Results The mean value of NT-proBNP was 160±137 pg/ml, and sST2 was 29±13, ng/ml in the entire population. Mean NT-proBNP was significantly higher in patients with severe PR (169±150 vs145±118, pg/ml, p<0.001), while similar sST2 levels were observed in both groups (29±14 vs30±12, ng/ml, p>0.05). NT-proBNP and sST2 levels were higher in patients with transannular patch when compared to other RVOT intervention. Both biomarkers were significantly associated with exercise capacity, but NT-proBNP (r=-.60, p<0.001) was stronger. The optimal cut-off of 90pg/ml for NT-proBNP had a sensitivity of 74% and specificity of 63% for detection of impaired exercise capacity. Conclusions Serum levels of sST2 and NT-proBNP are elevated in patients with repaired TOF, with higher values observed in those with severe PR, but also in patients undergoing transannular patch. Incorporating both markers in these patients increased the ability to detect impairment in exercise capacity.

Circulating soluble suppression of tumorigenicity-2 and the recurrence of atrial fibrillation after catheter ablation: A meta-analysis.

Soluble suppression of tumorigenicity-2 (sST-2), a marker of myocardial fibrosis and remodeling, has been related to the development of atrial fibrillation (AF). The aim of this meta-analysis was to evaluate the relationship between baseline serum sST-2 levels and the risk of AF recurrence after ablation. Relevant observational studies were retrieved from PubMed, Web of Science, Embase, Wanfang and China National Knowledge Infrastructure (CNKI). A random-effects model was used to combine the data, accounting for between-study heterogeneity. Fourteen prospective cohorts were included. Pooled results showed higher sST-2 levels before ablation in patients with AF recurrence compared to those without AF recurrence (standardized mean difference = 1.15, 95% confidence interval [CI] = 0.67 to 1.63, P < 0.001; I2 = 92%). Meta-regression analysis suggested that the proportion of patients with paroxysmal AF (PaAF) was positively related to the difference in serum sST-2 levels between patients with and without AF recurrence (coefficient = 0.033, P < 0.001). Subgroup analysis showed a more remarkable difference in serum sST-2 levels between patients with and without AF recurrence in studies where PaAF was ≥ 60% compared to those where it was < 60% (P = 0.007). Further analyses showed that high sST-2 levels before ablation were associated with an increased risk of AF recurrence (odds ratio [OR] per 1 ng/mL increment of sST-2 =1.05, OR for high versus low sST-2 = 1.73, both P values < 0.05). In conclusion, high sST-2 baseline levels may be associated with an increased risk of AF recurrence after catheter ablation.

. The significance of serum sST2 and cfDNA in children with severe pneumonia complicated by myocardial damage

Objective: The paper aimed to explore the significance of serum sST2 and cfDNA to prevent atrial inflammation in children with severe pneumonia complicated by myocardial damage. Methods: 120 children with severe pneumonia complicated by myocardial damage who were treated in the Children's Department of the author's hospital from April 2021 to December 2023 were recruited as research subjects. The children were randomly divided into two groups, one group of 60 children received personalized care intervention based on serum sST2 and cfDNA (personalized care group), and the other group of 60 children received routine care (routine care group). The clinical data of the two groups of patients were compared. The changes in serum sST2 and cfDNA levels of patients were compared before and after care. ELISA kits were used to test atrial inflammation marker levels before and after patient care. The patient's cardiac function was assessed through cardiac ultrasound. the nursing intervention effects of the two groups was compared. The patient satisfaction with nursing care was compared between the two groups. Results: There was no distinction in the general record of the two groups (P&gt;0.05). Before care, there was no distinction in serum sST2 and cfDNA levels between the two groups (P&gt;0.05). After care, the serum sST2 and cfDNA levels in the personalized care group were lower than those in the routine care group (P&lt;0.05). There was no difference in CRP, cTn, 1L-6 and TNF-α between the two groups before nursing (P&gt;0.05). After nursing, the levels of CRP, cTn, 1L-6 and TNF-α in personalized nursing were lower than those in the conventional nursing group (P&lt;0.05). Parameters such as EF and E/A in the personalized care group were higher than those in the routine care group (P&lt;0.05). The LVEDd and LVESd in the personalized care group were smaller than routine care group (P&lt;0.05). The improvement rate of cardiac function, remission rate of atrial inflammation and 6-month re-hospitalization rate in the personalized care group were lower than conventional care group (P&lt;0.05). The very satisfied rate in the personalized care group was higher than routine care group (P&lt;0.05), and the dissatisfaction rate in the personalized care group was lower than routine care group (P&lt;0.05). Conclusion: Personalized nursing intervention based on serum sST2 and cfDNA can significantly improve the cardiac function of children with severe pneumonia complicated by myocardial damage, reduce the levels of atrial inflammation markers, and advance the satisfaction of children and their families. These findings underscore the importance of applying serum sST2 and cfDNA monitoring in clinical care and the significant benefits of personalized care in preventing atrial inflammation, improving heart health, and improving patient quality of life.

Assessment of combined serum sST2 and AFP levels in the diagnosis of hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is a common malignant tumor with high morbidity and mortality. Alpha-fetoprotein (AFP) is the most widely used diagnostic serum biomarker, but it still has limited accuracy in detecting HCC, suggesting the necessity of seeking more ideal biomarkers with high sensitivity and specificity. Soluble growth stimulation gene 2 (sST2) form of growth stimulating expression gene 2 (ST2), is expressed in various organs and can bind competitively to interleukin 33 (IL-33). Whether sST2 can serve as a serum biomarker for HCC is largely unknown. Objective To investigate the value of sST2 as a serum diagnostic marker for HCC. Methods This study included 93 newly diagnosed HCC patients (HCC group), 90 chronic hepatitis B patients (CHB group), and 90 healthy individuals (HCs group). Spearman correlation analysis was used to explore the relationships between sST2 and the experimental indicators in HCC group. The receiver operating characteristic (ROC) curve evaluated the efficacy of sST2 alone or in combination with AFP in the diagnosis of HCC. Result The median level of sST2 was significantly higher in HCC group (24.00 [15.20-49.90] ng/mL) compared to CHB group (19.55 [15.23-24.95] ng/mL) and HCs group (7.65 [5.20-10.53] ng/mL). No significant correlations were found between sST2 and other clinical indicators in HCC group. The Area Under Curve (AUC) of ROC curve to distinguish HCC patients from healthy controls and CHB group was 0.861 (sensitivity 82.80%, specificity 72.10%) and 0.709 (sensitivity 80.60%, specificity 52.50%), respectively. When combined with AFP, the AUC increased to 0.963 (sensitivity 82.90%, specificity 94.20%), and 0.895 (sensitivity 72.0%, specificity 100%), respectively. Conclusions The serum level of sST2 increased in HCC and its diagnostic performance is comparable to that of AFP, supporting its potential as a promising biomarker for detection of HCC. The combined use of sST2 and AFP enhances diagnostic efficacy for HCC.

Serum Soluble Suppression of Tumorigenicity-2 Levels Predict Cardiovascular Events in Patients Undergoing Incident Peritoneal Dialysis: A Prospective Cohort Study.

Biomarkers are urgently required to identify peritoneal dialysis (PD) patients at risk of cardiovascular (CV) events. This study aimed to investigate the predictive value of soluble suppression of tumorigenicity-2 (sST2) for CV events in patients undergoing incident PD. In this prospective cohort study, incident PD patients were enrolled. Blood samples to measure sST2 levels were obtained before PD catheter implantation. The patients underwent a standard peritoneal equilibration test (PET) after initiation of PD for 4-6 weeks. The sST2 levels in both serum and dialysate were determined using enzyme-linked immunosorbent assay. CV events were recorded during the follow-up period. A total of 137 patients were enrolled. During the follow-up period of 17.3 months, 49 (35.76%) patients experienced CV events. When patients were dichotomized based on the median values and the calculated cutoff values of sST2, the higher sST2 group had 2.980- and 3.048-fold increased risks of CV events, respectively, when compared with the lower sST2 group. Moreover, the prognostic value of sST2 remained significant as a continuous variable (per 1 standard deviation increase, hazard ratio [HR] = 1.037, 95% confidence interval [CI] 1.010-1.066, p = 0.008). N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were found to indicate a higher risk only when dichotomized based on the calculated cutoff values. Furthermore, serum sST2 and NT-proBNP levels simultaneously above the calculated cutoff values were associated with a higher risk of CV events (HR = 3.398, 95% CI 1.813-6.367, p &lt; 0.001). Baseline serum sST2 level is an independent predictor of the risk of CV events in patients receiving incident PD, and in combination with NT-proBNP level, it can provide a more accurate predictive value.

ST2 and IL-33 polymorphisms and the development of childhood asthma: a prospective birth cohort study in Finnish children.

The ST2/IL-33 signaling pathway has an important role in the host inflammatory response. Here we aimed to study the association of ST2 and IL-33 polymorphisms with serum soluble (s) ST2 and IL-33 concentrations in healthy Finnish children and, in addition, their association with childhood asthma. In total, 146 children were followed from birth to the age 7 years for the development of asthma. Single-nucleotide polymorphisms (SNPs) in ST2 and IL-33 were determined, and associations of the SNP variants with serum levels of sST2 and IL-33 at age of 13 months and with recurrent wheezing and childhood asthma at 7 years of age were analyzed. Children with ST2 rs1041973 AC/AA genotypes had significantly lower level of serum sST2 (2453 pg/mL; IQR 2265) than those with CC genotype (5437 pg/mL; IQR 2575; p = < 0.0001). Similar difference was also observed with ST2 rs13408661. No differences were observed between subjects with studied IL-33 SNPs. Children who carried genetic variants of ST2 rs1041973 or rs13408661 seemed to have a higher risk of asthma. In contrast, children who carried genetic variants of IL-33 rs12551268 were less often diagnosed with asthma. Even though these SNPs seemed to associate with asthma, the differences were not statistically significant.

ST2 levels and neurodegenerative diseases: is this a significant relation?

Interleukin-33 (IL-33), belonging to the interleukin-1 cytokine family, has a decoy receptor soluble ST2 (sST2). IL-33 is found in oligodendrocytes and astrocytes and is involved in central nervous system healing and repair, whereas ST2 is found in microglia and astrocytes. Some studies have found a link between changes in the IL-33/ST2 pathway and neurodegenerative disorders. This review article investigates the relationship between the interleukin-33 (IL-33)/ST2 pathway and neurodegenerative disorders. It was discovered that soluble st2 levels were increased. Furthermore, IL-33 levels were found to be lower in many neurodegenerative diseases such as Alzheimer's and amyotrophic lateral sclerosis (ALS). The association with other disorders, such as ankylosing spondylitis, multiple sclerosis, and systemic lupus erythematosus (SLE), was also observed. Various studies suggest that ST2/IL-33 signalling may be pivotal in the disease modulation of neurodegenerative disorders. The serum sST2 level test can be useful in determining the inflammatory status and severity of illness in many neurodegenerative disorders. In this review, we will discuss recent findings concerning the interleukin-33 (IL-33)/ST2 pathway and its role in the diagnosis and treatment of diseases with neurodegeneration.

Soluble ST2 and its relation to inflammatory, vascular atherosclerotic, and calcification markers in patients with atrial fibrillation or heart failure at moderate-to-high cardiovascular risk

Background: Cardiovascular diseases (CVDs) are the major cause of death globally. Among them, heart failure (HF) and atrial fibrillation (AF) result in poor prognosis and quality of life. Standard methods for assessing AF and HF, through history and physical examination, have limited sensitivity and specificity, which lead to delayed diagnosis and high risk of mortality. The identification of biomarkers able to detect the early stages of disease and/or their progression is of great importance for improving the clinical outcome. As AF and HF often coexist, it would be of great importance to find a biomarker with diagnostic utility in predicting HF in AF patients. Soluble suppression of tumorigenesis-2 (sST2) is a part of the cardioprotective IL-33/ST2 signaling pathway and may serve as a candidate biomarker for HF and AF. We aimed to evaluate sST2 serum levels in patients with AF and HF with preserved ejection fraction (HFpEF) and to explore potential relationships with traditional CVD risk factors and with novel biomarkers for vascular calcification such as undercarboxylated matrix Gla-protein (ucMGP). Materials and Methods: This study included 99 patients stratified into three groups: HFpEF (n=19), paroxysmal or persistent AF in sinus rhythm (n=33), and control group without CVD but at moderate-to-high CVD risk (n=47). Hemodynamic and anthropometric measures, coronary artery calcification (CAC), routine laboratory parameters, circulating ucMGP, and sST2 were measured. Results: sST2 levels were highly elevated in HFpEF patients. Significant positive correlation was found between sST2 and CAC-score (r=0.237, p=0.039), negative relations with serum lipids in AF patients, and positive association with serum C-reactive protein (r=0.609, p=0.018) in HFpEF patients. Soluble ST2 positively correlates with ucMGP in the entire studied population (r=0.252, p=0.006) and in the combined CVD group (AF+HFpEF) (r=0.254, p=0.036). Conclusions: sST2 levels emerge as a novel biomarker in CVD and may have prognostic importance for HF prediction in AF patients.

Relationship between serum soluble suppression of tumorigenicity (ST) 2 and global longitudinal strain in early onset preeclampsia

BackgroundPreeclampsia is one of the leading causes of death in childbearing women worldwide. Hemodynamic changes in preeclampsia can trigger cardiac remodeling as indicated by increase of soluble-ST2 (sST2). Global longitudinal strain were able to detect systolic dysfunction better than the ejection fraction. This study aims to evaluate the correlation between serum levels of sST2 towards GLS in patients with early-onset preeclampsia.MethodsThis is a cross-sectional observational study with correlation analysis. Subjects were patients with severe preeclampsia with gestational age before 34 weeks at Dr. Hasan Sadikin Central General Hospital Bandung and Bandung Kiwari Regional General Hospital from June to August 2022. Examination of sST2 was carried out through blood samples using the ELISA method. sST2 was measured using Presage ST2 Assay reagent. GLS examination was carried out using speckle tracking technique with EchoPAC. Correlation analysis was conducted using the Pearson test if normally distributed, otherwise Spearman’s correlation was conducted. Correlation analysis was followed by linear regression.ResultsA total of 30 patients met the inclusion criteria. The mean age was 30.83 ± 7.09, with 17 (56.7%) multiparous patients. The median sST2 was 145.75 ng/mL, and the median GLS was − 17.4%. Spearman correlation analysis showed that there was a significant positive correlation with moderate strength between sST2 and GLS (r = 0.583; p < 0.002). Linear regression showed that every 1 ng/ml increase in sST2 would give an increase in GLS of 0.014%.ConclusionThere is a significant correlation between sST2 and GLS in patients with early onset severe preeclampsia.

Testosterone and soluble ST2 as mortality predictive biomarkers in male patients with sepsis-induced cardiomyopathy.

Sepsis-induced cardiomyopathy (SIC) is characterized by high mortality and poor outcomes. This study aimed to explore the relationship between testosterone and soluble ST2 (sST2) and all-cause mortality in patients with SIC. Clinical data from SIC patients at Renmin Hospital of Wuhan University from January 2021 and March 2023 were reviewed. Serum testosterone and sST2 were measured at admission. Kaplan-Meier analysis and receiver operative characteristic curve (ROC) were used to estimate the predictive values of testosterone and sST2 on 28 days and 90 days mortality of SIC. A total of 327 male subjects with SIC were enrolled in this study. During the 28 days and 90 days follow-up, 87 (26.6%) and 103 deaths (31.5%) occurred, respectively. Kaplan-Meier analysis showed significantly higher 28 days and 90 days survival in patients with higher testosterone and decreased sST2 levels (p < 0.001). Testosterone, sST2, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were significantly associated with 28 days and 90 days mortality (p < 0.05). Partial correlation analysis showed strong positive correlation between testosterone and left ventricular ejection fraction (LVEF) (p < 0.001), and negative correlation between testosterone and sST2 (p < 0.001), high-sensitivity troponin I (hs-TnI) levels (p < 0.001) and smoke history (p < 0.01). The concentrations of sST2 were positively related with E/e' ratio (p < 0.001), and negatively correlated with TAPSE (p < 0.001). The combination of testosterone and sST2 enhanced the prediction of both 28 days [area under the ROC curve (AUC), 0.805] and 90 days mortality (AUC, 0.833). Early serum testosterone and sST2 levels could predict mortality of SIC independently and jointly. Further research is needed to determine the utility of biochemical markers in identifying high-risk patients with SIC.

Predictive Value of Serum Soluble ST2 in Adult Patients Undergoing Cardiac Surgery for Acute Kidney Injury.

Cardiac surgery is related to an increased risk of postoperative acute kidney injury (AKI). Serum soluble ST2 (sST2) is highly predictive of several cardiovascular diseases and may also be involved in renal injury. This study explored the relationship between serum sST2 levels measured at intensive care unit (ICU) admission and the development of AKI after cardiac surgery. We prospectively conducted an investigation on consecutive patients who underwent cardiac surgery. sST2 was immediately measured at ICU admission. The relationship between the levels of sST2 and the development of AKI was explored using stepwise logistic regression. Among the 500 patients enrolled, AKI was observed in 207 (41%) patients. Serum sST2 levels in AKI patients were higher than those without AKI (61.46 ng/mL [46.52, 116.25] vs. 38.91 ng/mL [28.74, 50.93], p &lt; 0.001). Additionally, multivariable logistic regression analysis showed that as progressively higher tertiles of serum sST2, the odds ratios (ORs) of AKI gradually increased (adjusted ORs of 1.97 [95% CI, 1.13-3.45], and 4.27 [95% CI, 2.36-7.71] for tertiles 2 and 3, respectively, relative to tertile 1, p &lt; 0.05). The addition of sST2 further improved reclassification (p &lt; 0.001) and discrimination (p &lt; 0.001) over the basic model, which included established risk factors. Serum sST2 levels at ICU admission were associated with the development of postoperative AKI and improved the identification of AKI after cardiac surgery.

ST2-Mediated Neutrophilic Airway Inflammation: A Therapeutic Target for Patients With Uncontrolled Asthma.

Suppression of tumorigenicity 2 (ST2) has been proposed as the receptor contributing to neutrophilic inflammation in patients with type 2-low asthma. However, the exact role of ST2 in neutrophil activation remains poorly understood. A total of 105 asthmatic patients (classified into 3 groups according to control status: the controlled asthma [CA], partly-controlled asthma [PA], and uncontrolled asthma [UA] groups), and 104 healthy controls were enrolled to compare serum levels of soluble ST2 (sST2) and interleukin (IL)-33. Moreover, the functions of ST2 in neutrophils and macrophages (Mϕ) were evaluated ex vivo and in vivo. Serum sST2 levels were significantly higher in the UA group than in the CA or PA groups (P < 0.05 for all) with a negative correlation between serum sST2 and forced expiratory volume in 1 second % (r = -0.203, P = 0.038). Significantly higher expression of ST2 receptors on peripheral neutrophils was noted in the UA group than in the PA or CA groups. IL-33 exerted its effects on the production of reactive oxygen species, the formation of extracellular traps from neutrophils, and Mϕ polarization/activation. In neutrophilic asthmatic mice, treatment with anti-ST2 antibody significantly suppressed proinflammatory cytokines (tumor necrosis factor-alpha and IL-17A) as well as the numbers of immune cells (neutrophils, Mϕ, and group 3 innate lymphoid cells) in the lungs. These results suggest that IL-33 induces the activation of neutrophils and Mϕ via ST2 receptors, leading to neutrophilic airway inflammation and poor control status of asthma. ST2 could be a therapeutic target for neutrophilic airway inflammation in patients with UA.

Diagnostic potential of soluble ST2 and D-dimer for Stanford Type B aortic dissection and intramural aortic hematoma

ObjectiveType B aortic dissection (TBAD) and intramural aortic hematoma (IMH) are common manifestations of Acute Aortic Syndrome (AAS), exhibiting overlapping clinical features. The timely and accurate diagnosis and differentiation between TBAD and IMH are critical for appropriate management. Tumorigenicity 2 (sST2) and D-dimer have been shown to elevate levels in both TBAD and IMH, making them valuable as “rule-out” markers. Hence, we aimed to assess the diagnostic utility of sST2 and D-dimer in distinguishing TBAD from IMH. MethodsIn this retrospective study, we analyzed serum levels of sST2 and D-dimer in 182 AAS patients, comprising 90 TBAD cases, 92 IMH cases, and 90 non-AAS cases. Serial measurements were taken at 1 h, 6 h, 12 h, 24 h, and 72 h post-admission. Comparative analyses were conducted between TBAD and non-AAS cases, IMH and non-AAS cases, and TBAD and IMH cases. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of sST2 and D-dimer in identifying TBAD or IMH cases. ResultsBoth TBAD and IMH patients displayed elevated levels of sST2 and D-dimer compared to non-AAS cases. Notably, sST2 levels were significantly higher in TBAD patients than in IMH patients, whereas D-dimer levels exhibited moderate differences. TBAD patients tended to exhibit elevated levels of either sST2 or D-dimer, with a modest correlation between the two (Pearson correlation coefficient = 0.3614). In contrast, IMH patients showed elevations in both markers, with a positive correlation between them (Pearson correlation coefficient = 0.6814). The ROC analysis revealed that both sST2 (AUC, 0.657; 95 % CI, 0.552–0.753; cutoff value, 27.54 ng/ml) and D-dimer (AUC, 0.695; 95 % CI, 0.591–0.787, cutoff value, 1.215 ng/ml) demonstrated favorable diagnostic performance for TBAD. sST2 exhibited a sensitivity of 80.92 % and a specificity of 75.00 %, while D-dimer showed a sensitivity of 80.92 % and a specificity of 75.00 %. For the diagnosis of IMH, the combined assessment of sST2 and D-dimer (AUC, 0.674; 95 % CI, 0.599–0.768; sensitivity, 69.20 %; specificity, 80.00 %) proved effective. ConclusionsOur results indicate that both sST2 and D-dimer show diagnostic potential for TBAD. Elevated levels of either serve as an indicator of TBAD onset. However, concurrent elevation of both markers seems to be indicative of IMH. The combination of increased sST2 and D-dimer levels demonstrates strong diagnostic performance in identifying IMH cases.

Soluble suppression of tumorigenicity 2 is a potential predictor of post-liver transplant renal outcomes.

Acute kidney injury is considered an independent prognostic factor for mortality in patients with liver cirrhosis. Non-treated acute kidney injury can progress to hepatorenal syndrome with a poor prognosis. As suppression of tumorigenicity 2 (ST2) is a member of the interleukin-1 receptor family that aggravates inflammation and fibrotic changes in multiple organs, we measured soluble ST2 (sST2) level in the serum and urine of liver-transplant recipients at the time of transplantation. The serum sST2 level significantly increased in liver-transplant recipients with suppressed kidney function compared with that in recipients with normal function. In recipients with severely decreased liver function (model for end-stage liver disease score ≥ 30), the serum sST2 level was higher than that in recipients with preserved liver function (model for end-stage liver disease score ≤ 20, P = 0.028). The serum sST2 level in recipients with hepatorenal syndrome was higher than that in liver-transplant recipients without hepatorenal syndrome (P = 0.003). The serum sST2 level in patients with hepatorenal syndrome was higher than that in recipients without a history of acute kidney injury (P = 0.004). Recipients with hepatorenal syndrome and recovered kidney function showed higher sST2 levels than those who did not recover (P = 0.034). Collectively, an increase in the serum sST2 level reflects a decrease in both kidney and liver functions. Thus, measuring sST2 level at the time of liver transplantation can help predict renal outcomes.

Exploring the significance of interleukin-33/ST2 axis in minimal change disease

Minimal change disease (MCD), a common cause of idiopathic nephrotic syndrome, has been postulated to exhibit an association with allergic conditions. Recent studies revealed the crucial role of interleukin (IL)-33 in type 2 innate immunity. We hypothesized that development of MCD involves an IL-33–related immune response. We examined 49 patients with biopsy-proven MCD, 6 healthy volunteers, and 29 patients in remission. In addition to clinical features, serum and urinary levels of IL-33 and soluble suppression of tumorigenicity 2 protein (sST2), a secreted form of the receptor of IL-33, were analyzed. Although IL-33 was barely detectable in either MCD or control samples, sST2 levels at diagnosis were elevated in MCD patients. Serum sST2 levels of MCD patients were correlated with serum total protein level (r = − 0.36, p = 0.010) and serum creatinine level (r = 0.34, p = 0.016). Furthermore, the elevated sST2 levels were observed to decrease following remission. Immunofluorescence revealed IL-33 expression in the podocytes among MCD patients, with a significant increase compared with controls. In vitro, mouse podocyte cells incubated with serum from a MCD patient at disease onset showed increased IL-33 secretion. These results suggest an IL-33–related immune response plays a role in MCD.

Association of soluble ST2 with disease activity in pediatric systemic lupus erythematosus

ObjectiveThe aim of this study is to assess soluble ST2 (sST2) as a potential biomarker in pediatric systemic lupus erythematous patients (pSLEs), especially to reveal the association of the sST2 levels with the disease activity and other laboratory tests. MethodsA total of 65 pSLEs and 33 age- and sex- matched healthy controls (HCs) were enrolled in this study between July and December 2022 from Children’s Hospital of Fudan University. Serum levels of sST2 were determined and clinical information and laboratory test results were collected. ResultsSerum sST2 levels were significantly increased in pSLEs (36.7 ng/mL, IQR 16.6–76.9) compared with HCs (10.4 ng/mL, IQR 6.4–14.8). Patients with moderate to severe disease activities had significantly elevated levels of sST2 compared with those with inactive and mild disease activities. A positive correlation was found between sST2 levels and SLE Disease Activity Index-2000 (SLEDAI-2K) scores. The serum levels of sST2 also showed positive correlations with anti-dsDNA antibody, ALT, AST, GGT, blood urea, and negative correlations with C3, C4, CH50 and ALP. ROC analysis showed that sST2 could discriminate active disease (AUC: 0.959, 95 %CI 0.878–0.992) with an optimal cut-off of 30.2 ng/mL (sensitivity: 89.7 %, specificity: 100 %) and moderate/severe disease activities (AUC: 0.962, 95 %CI 0.883–0.994) with an optimal cut-off of 45.2 ng/mL (sensitivity: 91.7 %, specificity: 90.2 %). Decreased sST2 levels were observed after clinical treatment. ConclusionsElevated serum sST2 level in pSLEs were observed and were highly associated with disease activity, suggesting sST2 might be a potential biomarker for pSLEs.

Dynamics of global longitudinal strain of the left ventricular myocardium and blood biomarker levels in patients with rheumatoid arthritis treated with biologic disease-modifying antirheumatic drugs or Janus kinase inhibitors

Objective: to study the dynamics of global longitudinal myocardial strain (GLS) using echocardiography (speckle tracking method) and blood biomarker levels (NT -proBNP, soluble ST2, sST2) in RA patients against a background of 12 months of therapy with biological disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (JAKi). Material and methods. The study included 50 patients with RA (ACR/EULAR criteria, 2010): 84 % were women, median age 51.0 [40.0; 59.0] years, median duration of RA was 4.5 [3.0; 14.0] years, median DAS28 5.7 [5.2; 6.4] points. 78 % of patients were positive for IgM rheumatoid factor, 66 % for antibodies to cyclic citrullinated peptide. At the time of inclusion in the study, 38% of patients were receiving methotrexate, 38 % – leflunomide, 10 % – sulfasalazine, 12 % – hydroxychloroquine, 70 % – glucocorticoids, 82 % – nonsteroidal anti-inflammatory drugs. 60 % of patients with RA had a history of inadequate efficacy of two or more DMARDs. After examination, all patients were prescribed bDMARDs or JAKi. TNF-α inhibitors were given to 38% of patients, anti-B-cell therapy – to 50% of patients, IL-6 inhibitors – to 4%, T-lymphocyte costimulation blockers – to 2 %, JAKi – to 6 % of RA patients. All patients with RA were examined before administration of bDMARDs and in dynamics after 12 months of treatment. Echocardiography was performed – tissue Dopplerography and evaluation by speckle tracking method of left ventricular myocardium GLS (GLD LVM); in blood serum the levels of NT-proBNP, sST2 were determined. The normal range for NT-proBNP was less than 125 pg/ml, and for sST2 less than 17.65 ng/ml. The control group consisted of 20 healthy subjects who were comparable in sex and age. RA patients and subjects in the control group had no cardiovascular disease. Results and discussion. After 12 months of bDMARDs therapy, GLS LVM increased and the frequency of reduced GLS LVM decreased by 47 % (p &lt; 0.05). The indexed end-systolic volume of the left atrium also decreased. RA patients had higher values of NT-proBNP and sST2 compared to the control group (p &lt; 0.05). The variations of NT-proBNP level in blood serum of RA patients after 12 months of therapy were statistically insignificant (p = 0.5). The level of sST2 in the serum of patients with RA decreased significantly after 12 months of therapy compared to baseline (p &lt; 0.01). Direct correlations were found between the delta (Δ) of the level of sST2 and ΔDAS28, the level of ΔsST2 and ΔCRP, and ΔACCP. After 12 months of therapy, RA patients with persistent moderate/high disease activity had higher levels of systolic blood pressure and serum levels of NT-proBNP, lower left ventricular (LV) ejection fraction (LVEF) and GLS LVM than patients who had remission/low RA activity. There were no differences between groups in LVEF, LV size, LV myocardial mass index, and NT-proBNP levels. Negative correlations were observed between ΔGLD LVM and ΔESR and ΔsST2. Conclusion. In patients with RA, a decrease in disease activity on a background of therapy with bDMARDs and JAKi leads to an improvement in GLS LVM. Administration of bDMARDs in patients with active RA and established LV subclinical myocardial dysfunction may slow the progression of myocardial dysfunction. Serum sST2 and NT-proBNP levels were increased in patients with RA compared with the control group. After 12 months of therapy with bDMARDs, the level of sST2 in the serum of RA patients decreased significantly, and the level of NT-proBNP did not change in dynamics.

Serum levels of soluble suppression of tumorigenicity 2 (sST2) and heart-type fatty acid binding protein (H-FABP) independently predict in-hospital mortality in geriatric patients with COVID-19

Elevation of cardiac damage biomarkers is associated with adverse clinical outcomes and increased mortality in COVID-19 patients. This study assessed the association of admission serum levels of sST2 and H-FABP with in-hospital mortality in 191 geriatric patients (median age 86 yrs., IQR 82–91 yrs.) with COVID-19 and available measures of hs-cTnT and NT-proBNP at admission. Cox proportional hazards models were utilized to predict in-hospital mortality, considering clinical/biochemical confounders as covariates. A composite cardiac score was calculated to improve predictive accuracy. Patients deceased during their hospital stay (26%) exhibited higher levels of all biomarkers, which demonstrated good discrimination for in-hospital mortality. Addition of sST2 and H-FABP significantly improved the discriminatory power of hs-cTnT and NT-proBNP. The composite cardiac score (AUC=0.866) further enhanced the predictive accuracy. Crude and adjusted Cox regressions models revealed that both sST2 and H-FABP were independently associated with in-hospital mortality (HR for sST2 ≥129 ng/mL, 4.32 [1.48–12.59]; HR for H-FABP ≥18 ng/mL, 7.70 [2.12–28.01]). The composite cardiac score also independently correlated with in-hospital mortality (HR for 1-unit increase, 1.47 [1.14–1.90]). In older patients with COVID-19, sST2 and H-FABP demonstrated prognostic value, improving the predictive accuracy of the routinely assessed biomarkers hs-cTnT and NT-proBNP.

Serum Levels of Hcy, sST2 and CA-125 in CHF Patients and Their Correlation with Cardiac Function Classification.

The relationships between serum levels of homocysteine (Hcy), soluble stromelysin 2 (sST2), and tumor-associated cancer antigen 125 (CA-125) and heart failure requires further investigation. The aim of the present study was to evaluate the levels of Hcy, sST2 and CA-125 in patients with congestive heart failure and to correlate these with cardiac function, thereby providing a reference for the clinical diagnosis and treatment of heart failure. Seventy patients with chronic heart failure (CHF) diagnosed between August 2020 and July 2022 were classified into heart failure groups II (n = 25), III (n = 23) and IV (n = 22). Seventy individuals with normal physical examination results were selected as the healthy group. Serum Hcy, sST2 and CA-125 levels for all participants were evaluated and correlated with each other and with cardiac function classification. The diagnostic value of individual Hcy, sST2, CA-125 levels for CHF was evaluated, as well as a combination of these factors. Hcy, sST2, and CA-125 levels were lower in the healthy group than in the heart failure group. Moreover, a progressive increase in Hcy, sST2, and CA-125 levels were observed in heart failure groups II, III, and IV. Individual Hcy, sST2 and CA-125 levels, as well as a combination of these factors, were significantly correlated with cardiac function classification (p < 0.05). Hcy, sST2 and CA-125 levels each showed diagnostic value for CHF, with the three combined having the best diagnostic value. Abnormally high levels of Hcy, sST2 and CA-125 occur in CHF patients and are positively correlated with cardiac function classification. Individual levels of these factors, and particularly a combination of the three, show good sensitivity and specificity for CHF diagnosis that could be widely used in clinical practice.

THE ASSOCIATION BETWEEN SERUM SOLUBLE ST2 CONCENTRATION AND SOME CLINICAL AND SUBCLINICAL INDICES IN PATIENTS WITH CHRONIC HEART FAILURE

Objectives: To investigate the level of serum soluble ST2 (sST2) and its association with some clinical and subclinical indices in patients with chronic heart failure (HF). Methods: A prospective cohort study was performed on 116 patients diagnosed with chronic HF at the Cardiology Department, Military Hospital 103, Hanoi and Cardiology Department, 19-8 Hospital - Ministry of Public Security, Hanoi, Vietnam, and 40 control patients at General Health Examination Department, Military Hospital 103, Hanoi from November 1, 2019 to September 30, 2022. Serum sST2 was measured using an enzyme-linked immunosorbent assay. Results: The mean age (± standard deviation) of patients with chronic HF was 68.3 (± 15.9) years, with 57.8% of the total patients who showed their age was &gt; 65 years. The median serum sST2 level in the group of patients with chronic HF (median: 5.89 ng/mL) was significantly higher than those in the control group (median: 2.39 ng/ml) (p &lt; 0.05). Serum sST2 level increased as LVEF decreased, with the highest level in HF with reduced EF patient group, followed by HF with mildly reduced EF, and HF with preserved EF groups. Serum sST2 level had a significant, positive correlation with heart rate in chronic HF patients. The serum sST2 level in the group of NYHA class IV was significantly higher than those in the group of NYHA class III and II (p &lt; 0.05). Conclusion: The level of serum sST2 increased in chronic HF patients. Serum sST2 level associated with left ventricular ejection fraction, and NYHA classification in chronic HF patients.