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

BACKGROUND： 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（s ST2） in HBV-ACLF.METHODS： Serum levels of IL-33 and sS T2 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.RESULTS： There was no significant difference of serum IL-33 level among HC, CHB and HBV-ACLF patients at week 1.However, serum s ST2 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 s ST2 level and the survival of HBV-ACLF patients. The level of serum s ST2 in HBV-ACLF survivors was significantly declined from week 1 to week 4 following the treatment, whereas that in HBV-ACLF nonsurvivors remained at a high level during the same period. Furthermore, serum sS T2 level was significantly correlated with laboratory parameters and the most updated prognostic scores（CLIF-C OF score, CLIF-C ACLF score and ACLF grades）. Thereceiver operating characteristics curves demonstrated that serum sS T2 level was a good diagnostic marker for predicting the 6-month mortality in HBV-ACLF patients, comparable to the most updated prognostic scores. Serum sS T2 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 sS T2 level above the cut-off point often had a worse prognosis than those below the cut-off point.CONCLUSION： Serum s ST2 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.

Early cardiopulmonary resuscitation on serum levels of myeloperoxidase,soluble ST2,and hypersensitive C-reactive protein in acute myocardial infarction patients

BACKGROUND Prompt and effective cardiopulmonary resuscitation(CPR)can promote the recovery of spontaneous circulation to some extent and can save patients’lives.The minimum target of cardiac resuscitation is the restoration of spontaneous circulation(ROSC).However,owing to prolonged sudden cardiac arrest,there is relatively high mortality within 24 h after cardiac resuscitation.Moreover,severe cerebral anoxia can deteriorate the prognosis of patients.Therefore,it is important to adopt an effective clinical evaluation of acute myocardial infarct(AMI)patients’prognosis after cardiac resuscitation for the purpose of prevention and management.AIM To investigate early CPR effects on human myeloperoxidase(MPO),soluble ST2(sST2),and hypersensitive C-reactive protein(hs-CRP)levels in AMI patients.METHODS In total,54 patients with cardiac arrest caused by AMI in our hospital were selected as the observation group,and 50 other patients with AMI were selected as the control group.The differences in serum levels of MPO,sST2,and hs-CRP between the observation group and the control group were tested,and the differences in the serum levels of MPO,sST2,and hs-CRP in ROSC and non-ROSC patients,and in patients who died and in those who survived,were analyzed.RESULTS Serum levels of MPO,sST2,hs-CRP,lactic acid,creatine kinase isoenzyme(CKMB),and cardiac troponin I(cTnI)were significantly higher in the observation group than in the control group(P<0.05).Serum levels of MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI in the observation group were lower after CPR than before CPR(P<0.05).In the observation group,MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI serum levels were lower in ROSC patients than in non-ROSC patients(P<0.05).MPO,sST2,hs-CRP,and lactic acid serum levels of patients who died in the observation group were higher than those of patients who survived(P<0.05).The areas under receiver operating characteristic curve predicted by MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI were 0.616,0.681,0.705,0.704,0.702,and 0.656,respectively(P<0.05).The areas under receiver operating characteristic curve for MPO,SST2,hs-CRP,and lactic acid to predict death were 0.724,0.800,0.689,and 0.691,respectively(P<0.05).Logistic regression analysis showed that MPO,sST2,and hs-CRP were the influencing factors of ROSC[odds ratios=1.667,1.589,and 1.409,P<0.05],while MPO,sST2,hs-CRP,and lactic acid were the influencing factors of death(odds ratios=1.624,1.525,1.451,and 1.365,P<0.05).CONCLUSION Serum levels of MPO,sST2,hs-CRP,and lactic acid have a certain value in predicting recovery and prognosis of patients with ROSC.

Predicting value of serum soluble ST2 and interleukin-33 for risk stratification and prognosis in patients with acute myocardial infarction

Background Acute myocardial infarction （AMI） is a common cardiac emergency with high mortality.Serum soluble ST2 （sST2） is a new emerging biomarker of cardiac diseases.The present study is to investigate the predictive value of sST2 and interleukin-33 （IL-33） for risk stratification and prognosis in patients with AMI.Methods Fifty-nine patients with AMI,whose chief complaint was chest pain or dyspnea,were selected for our study.Physical examination,chest radiograph,electrocardiograph （ECG）,biomarkers of myocardial infarction,NT-proBNP,echocardiography and other relevant examinations were performed to confirm the diagnosis of AMI.Thirty-six healthy people were chosen as the control group.Serum samples from these subjects （patients within 24 hours after acute attack） were collected and the levels of sST2 and IL-33 were assayed by enzyme-linked immuno-sorbent assay （ELISA） kit.The follow-up was performed on the 7th day,28th day,3rd month and 6th month after acute attack.According to the follow-up results we defined the end of observation as recurrence of AMI or any causes of death.Results Median sST2 level of the control group was 9.38ng/ml and that of AMI patients was 29.06ng/ml.Compared with the control group,sST2 expression in the AMI group was significantly different （P〈0.001）.In contrast,the IL-33 level showed no significant difference between the two groups.Serum sST2 was a predictive factor independent of other variables and may provide complementary information to NT-proBNP or GRACE risk score.IL-33 had no relationship to recurrence of AMI.Both sST2 and the IL-33/sST2 ratio were correlated with the 6-month prognosis; areas under the ROC curve were 0.938 and 0.920 respectively.Conclusions Early in the course （〈24 hours） of AMI,sST2 usually increases markedly.The increase of sST2 has an independent predictive value for the prognosis in AMI patients and provides complementary information to NT-proBNP or GRACE risk score.The IL-33/sST2 ratio correlates with the 6-month prognosis of AMI patients.However,there is no significant relationship between IL-33 and the prognosis of AMI patients.

Elevated Levels of Soluble ST2 were Associated with Rheumatoid Arthritis Disease Activity and Ameliorated Inflammation in Synovial Fibroblasts

Background：Much evidence has demonstrated that interleukin （IL）-33 plays an important role in rheumatoid arthritis （RA）.However,there have been limited studies about soluble ST2,a receptor for 1L-33,in RA.The aims of this study were to detect the levels of ST2 in the serum and synovial fluid of RA patients and to reveal the association of these levels with disease activity and the function of ST2 in RA.Methods：A total of 56 RA patients and 38 age-matched healthy controls were enrolled in this study.Synovial fluid samples were collected from another 30 RA patients and 20 osteoartbritis patients.Serum and synovial fluid levels of ST2 were measured by ELISA.In addition,the levels of ST2 in the serum of RA patients before and after therapy were detected.The function of ST2 in RA was revealed by the results of an in vitro cell assay,where recombinant ST2 proteins were used to treat peripheral blood mononuclear cells （PBMCs） and RA synovial fibroblasts （RASFs）.Results：Serum-soluble ST2 levels were significantly higher in RA patients （127.14 ± 61.43 pg/ml） than those in healthy controls （78.37 ± 41.93 pg/ml,P 〈 0.01）.Synovial fluid-soluble ST2 levels （41.90 ± 33.58 pg/ml） were much higher in RA patients than those in osteoarthritis patients （19.71 ± 16.72 pg/ml,P 〈 0.05）.RA patients who received effective therapy for 6 months showed decreased serum-soluble ST2 levels （113.01 ± 53.90 pg/ml） compared to baseline （139.59 ± 68.36 pg/ml） （P =0.01）.RA patients with high disease activity had higher serum-soluble ST2 levels （162.02 ± 56.78 pg/ml） than those with low disease activity （94.67 ± 40.27 pg/ml,P =0.001）.Soluble ST2 did not affect IL-1β,IL-6,IL-8,or tumor necrosis factor-α （TNF-o） expression in PBMCs from RA patients.However,soluble ST2 ameliorated the expressions of IL-33 and IL-1 β but not that of IL-6,IL-8,or TNF-α in resting RASFs.Interestingly,in the RASFs stimulated by TNF-α plus IL-1 β,soluble ST2 showed extensive suppressive effects on the expression of IL-6,IL-8,and TNF-α.Conclusion：Elevated levels of ST2 in the serum and synovial fluid were associated with disease activity and ameliorated IL-33 expression and IL-33-induced inflammation in RASFs,suggesting that soluble ST2 might be a potential therapeutic candidate for RA.