ABSTRACT
BACKGROUND: S100ß is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100ß and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear. METHODS: Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100ß levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome. RESULTS: A total of 1072 patients were included in the analysis. The highest S100ß levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100ß level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: ß 36.853, 95% confidence interval (CI) 22.659-51.048, P < 0.001; non-dominant: ß 23.645, 95% CI 10.774-36.516, P = 0.007). However, serum S100ß levels at 24 h were more strongly associated with NIHSS scores at 24 h and 3-month unfavorable outcome in patients with dominant hemisphere stroke (NIHSS: ß 3.470, 95% CI 2.392-4.548, P < 0.001; 3-month outcome: odds ratio (OR) 5.436, 95% CI 2.936-10.064, P < 0.001) than in those with non-dominant hemisphere stroke (NIHSS: ß 0.326, 95% CI - 0.735-1.387, P = 0.547; 3-month outcome: OR 0.882, 95% CI 0.538-1.445, P = 0.619). The association of S100ß levels and HT was not significant in either stroke lateralization group. CONCLUSIONS: Serum S100ß levels 24 h after IVT were independently associated with HT, infarct volume, and prognosis in patients with IVT, which suggests the application value of serum S100ß in judging the degree of disease and predicting prognosis.
Subject(s)
S100 Calcium Binding Protein beta Subunit , Stroke , Thrombolytic Therapy , Humans , Prospective Studies , S100 Calcium Binding Protein beta Subunit/blood , Female , Male , Aged , Middle Aged , Prognosis , Thrombolytic Therapy/methods , Stroke/blood , Stroke/drug therapy , Biomarkers/blood , Aged, 80 and over , Administration, Intravenous , Treatment OutcomeABSTRACT
BACKGROUND: Despite the use of validated guidelines in the management of mild traumatic brain injury (mTBI), processes to limit unnecessary brain scans are still not sufficient and need to be improved. The use of blood biomarkers represents a relevant adjunct to identify patients at risk for intracranial injury requiring computed tomography (CT) scan. CONTENT: Biomarkers currently recommended in the management of mTBI in adults and children are discussed in this review. Protein S100 beta (S100B) is the best-documented blood biomarker due to its validation in large observational and interventional studies. Glial fibrillary acidic protein (GFAP) and ubiquitin carboxyterminal hydrolase L-1 (UCH-L1) have also recently demonstrated their usefulness in patients with mTBI. Preanalytical, analytical, and postanalytical performance are presented to aid in their interpretation in clinical practice. Finally, new perspectives on biomarkers and mTBI are discussed. SUMMARY: In adults, the inclusion of S100B in Scandinavian and French guidelines has reduced the need for CT scans by at least 30%. S100B has significant potential as a diagnostic biomarker, but limitations include its rapid half-life, which requires blood collection within 3â h of trauma, and its lack of neurospecificity. In 2018, the FDA approved the use of combined determination of GFAP and UCH-L1 to aid in the assessment of mTBI. Since 2022, new French guidelines also recommend the determination of GFAP and UCH-L1 in order to target a larger number of patients (sampling within 12â h post-injury) and optimize the reduction of CT scans. In the future, new cut-offs related to age and promising new biomarkers are expected for both diagnostic and prognostic applications.
Subject(s)
Biomarkers , S100 Calcium Binding Protein beta Subunit , Humans , Biomarkers/blood , S100 Calcium Binding Protein beta Subunit/blood , Glial Fibrillary Acidic Protein/blood , Ubiquitin Thiolesterase/blood , Brain Concussion/blood , Brain Concussion/diagnosis , Tomography, X-Ray ComputedABSTRACT
Experimental and clinical studies have indicated a potential role of the protein S100ß in the pathogenesis and phenotype of neurodegenerative diseases. However, its impact on spinocerebellar ataxia type 2 (SCA2) remains to be elucidated. The objective of the study is to determine the serum levels of S100ß in SCA2 and its relationship with molecular, clinical, cognitive, and peripheral inflammatory markers of the disease. Serum concentrations of S100ß were measured by enzyme-linked immunosorbent assay in 39 SCA2 subjects and 36 age- and gender-matched controls. Clinical scores of ataxia, non-ataxia symptoms, cognitive dysfunction, and some blood cell count-derived inflammatory indices were assessed. The SCA2 individuals manifested S100ß levels similar to the control group, at low nanomolar concentrations. However, the S100ß levels were directly associated with a better performance of cognitive evaluation within the SCA2 cohort. Moreover, the S100ß levels were inversely correlated with most peripheral inflammatory indices. Indeed, the neutrophil-to-lymphocyte ratio significantly mediated the effect of serum S100ß on cognitive performance, even after controlling for the ataxia severity in the causal mediation analysis. Our findings suggested that, within physiologic concentrations, the protein S100ß exerts a neuroprotective role against cognitive dysfunction in SCA2, likely via the suppression of pro-inflammatory mechanisms.
Subject(s)
Cognitive Dysfunction , Inflammation , S100 Calcium Binding Protein beta Subunit , Spinocerebellar Ataxias , Humans , S100 Calcium Binding Protein beta Subunit/blood , Female , Male , Cognitive Dysfunction/blood , Middle Aged , Spinocerebellar Ataxias/blood , Inflammation/blood , Adult , Biomarkers/blood , AgedABSTRACT
OBJECTIVES: To evaluate some confounding factors that influence the concentrations of S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl-terminal hydrolase L-1 (UCH-L1) in older individuals. Indeed, recent guidelines have proposed the combined use of S100B and the "GFAP-UCH-L1" mTBI test to rule out mild traumatic brain injuries (mTBI). As older adults are the most at risk of mTBI, it is particularly important to understand the confounding factors of those mTBI rule-out biomarkers in aging population. METHODS: The protein S100B and the "GFAP and UCH-L1" mTBI test were measured using Liaison XL (Diasorin) and Alinity I (Abbott), respectively, in 330 and 341 individuals with non-suspected mTBI from the SarcoPhAge cohort. RESULTS: S100B, GFAP and UCH-L1 were all significantly correlated with renal function whereas alcohol consumption, Geriatric Depression Score (GDS), smoking habits and anticoagulant intake were not associated with any of these three biomarkers. Body mass index (BMI) and age were associated with GFAP and UCH-L1 expression while sex and mini-mental state examination (MMSE) were only associated with GFAP. According to the manufacturer's cut-offs for mTBI rule-out, only 5.5â¯% of participants were positive for S100B whereas 66.9â¯% were positive for the "GFAP-UCH-L1" mTBI test. All positive "GFAP-UCH-L1" mTBI tests were GFAP+/UCH-L1-. Among individuals with cystatin C>1.55â¯mg/L, 25â¯% were positive for S100B while 90â¯% were positive for the mTBI test. CONCLUSIONS: Our data show that confounding factors have different impacts on the positivity rate of the "GFAP-UCH-L1" mTBI test compared to S100B.
Subject(s)
Biomarkers , Glial Fibrillary Acidic Protein , S100 Calcium Binding Protein beta Subunit , Ubiquitin Thiolesterase , Humans , S100 Calcium Binding Protein beta Subunit/blood , Glial Fibrillary Acidic Protein/blood , Ubiquitin Thiolesterase/blood , Biomarkers/blood , Male , Female , Aged , Aged, 80 and over , Aging , Brain Concussion/diagnosis , Brain Concussion/blood , Middle AgedABSTRACT
OBJECTIVES: Data in literature indicate that in patients suffering a minor head injury (MHI), biomarkers serum levels could be effective to predict the absence of intracranial injury (ICI) on head CT scan. Use of these biomarkers in case of patients taking oral anticoagulants who experience MHI is very limited. We investigated biomarkers as predictors of ICI in anticoagulated patients managed in an ED. METHODS: We conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24â¯h observation and a second CT scan. The outcome was delayed ICI (dICI), defined as ICI on the second CT scan after a first negative CT scan. We assessed the sensitivity (SE), specificity (SP), negative predictive value (NNV) and positive predictive value (PPV) of the biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in order to identify dICI. RESULTS: Our study population was of 234 patients with a negative first CT scan who underwent a second CT scan. The rate of dICI was 4.7â¯%. The NPV for the detection of dICI were respectively (IC 95â¯%): S100B 92.7â¯% (86.0-96.8â¯%,); ubiquitin C-terminal hydrolase-L1 (UCH-L1) 91.8â¯% (83.8-96.6â¯%); glial fibrillary protein (GFP) 100â¯% (83.2-100â¯%); TBI 100â¯% (66.4-100â¯%). The AUC for the detection of dICI was 0.407 for S100B, 0.563 for neuron-specific enolase (NSE), 0.510 for UCH-L1 and 0.720 for glial fibrillary acidic protein (GFAP), respectively. CONCLUSIONS: The NPV of the analyzed biomarkers were high and they potentially could limit the number of head CT scan for detecting dICI in anticoagulated patients suffering MHI. GFAP and Alinity TBI seem to be effective to rule out a dCI, but future trials are needed.
Subject(s)
Anticoagulants , Biomarkers , Craniocerebral Trauma , Glial Fibrillary Acidic Protein , Phosphopyruvate Hydratase , S100 Calcium Binding Protein beta Subunit , Tomography, X-Ray Computed , Ubiquitin Thiolesterase , Humans , S100 Calcium Binding Protein beta Subunit/blood , Prospective Studies , Ubiquitin Thiolesterase/blood , Biomarkers/blood , Glial Fibrillary Acidic Protein/blood , Male , Female , Phosphopyruvate Hydratase/blood , Aged , Craniocerebral Trauma/blood , Craniocerebral Trauma/diagnosis , Middle Aged , Anticoagulants/therapeutic use , Aged, 80 and overABSTRACT
BACKGROUND: Low concentrations of S100B have neurotrophic effects and can promote nerve growth and repair, which plays an essential role in the pathophysiological and histopathological alterations of major depressive disorder (MDD) during disease development. Studies have shown that plasma S100B levels are altered in patients with MDD. In this study, we investigated whether the plasma S100B levels in MDD differ between genders. METHODS: We studied 235 healthy controls (HCs) (90 males and 145 females) and 185 MDD patients (65 males and 120 females). Plasma S100B levels were detected via multifactor assay. The Mahalanobis distance method was used to detect the outliers of plasma S100B levels in the HC and MDD groups. The Kolmogorov-Smirnov test was used to test the normality of six groups of S100B samples. The Mann-Whitney test and Scheirer-Ray-Hare test were used for the comparison of S100B between diagnoses and genders, and the presence of a relationship between plasma S100B levels and demographic details or clinical traits was assessed using Spearman correlation analysis. RESULTS: All individuals in the HC group had plasma S100B levels that were significantly greater than those in the MDD group. In the MDD group, males presented significantly higher plasma S100B levels than females. In the male group, the plasma S100B levels in the HC group were significantly higher than those in the MDD group, while in the female group, no significant difference was found between the HC and MDD groups. In the male MDD subgroup, there was a positive correlation between plasma S100B levels and years of education. In the female MDD subgroup, there were negative correlations between plasma S100B levels and age and suicidal ideation. CONCLUSIONS: In summary, plasma S100B levels vary with gender and are decreased in MDD patients, which may be related to pathological alterations in glial cells.
Subject(s)
Depressive Disorder, Major , S100 Calcium Binding Protein beta Subunit , Humans , Depressive Disorder, Major/blood , Male , Female , S100 Calcium Binding Protein beta Subunit/blood , Adult , Sex Factors , Middle Aged , Sex Characteristics , Biomarkers/blood , Case-Control StudiesABSTRACT
Head injury is a potentially lethal and frequently occurring condition in the emergency department (ED). Reliable and fast diagnosis is important both for patients and flow in the ED. Circulating S100B is used to rule out the need for head computer tomography in low-risk patients with mild head injury. The flow of these patients through the ED would benefit from shorter turn-around time. Standard serum clotting tubes require 30-60 min clotting time, followed by an analysis time of 45 min. Here, we evaluated the performance of two alternative blood collection tubes; a rapid serum tube (RST) with a recommend clotting time of 5 min and a hirudin tube (HIR) for instant anticoagulation. S100B measurement was performed on paired blood samples from 221 subjects using a Roche Cobas 602 analyser. The performances of the alternative tubes were evaluated by method comparison to the standard serum clotting tube, repeatability and agreement of results obtained from alternative tubes compared with the standard clotting tube. Both alternative tubes had a minor positive bias (RST = 0.011 µg/L, HIR = 0.008 µg/L). The repeatability was 2% for RST and 10% for HIR, while being 4% for the standard clotting tube. In the agreement analysis, the positive and negative predictive values for RST were 62% and 100% while being 73% and 99% for HIR respectively. Our study suggests that RST is a feasible alternative to reduce laboratory turn-around time in S100b analysis.
Subject(s)
S100 Calcium Binding Protein beta Subunit , Humans , S100 Calcium Binding Protein beta Subunit/blood , Male , Female , Adult , Blood Specimen Collection/methods , Blood Specimen Collection/instrumentation , Middle Aged , Reproducibility of Results , Hirudins , Craniocerebral Trauma/blood , Craniocerebral Trauma/diagnosis , Craniocerebral Trauma/diagnostic imaging , AgedABSTRACT
BACKGROUND: This work aimed to analyze serum S100B levels and brain-derived neurotrophic factor (BDNF) in patients with lumbar disc prolapse to test their predictive values concerning the therapeutic efficacy of pulsed radiofrequency. METHODS: This prospective interventional study was carried out on 50 patients candidates for radiofrequency for treating symptomatic lumbar disc prolapse. Pain severity and functional disability were assessed using the Numeric Rating Scale (NRS) and Functional rating index (FRI) before as well as two weeks, 1, 3, and 6 months after the radiofrequency. Quantitative assessment of serum S100B level and BDNF was done for all the included patients one day before radiofrequency. RESULTS: The scores of NRS and FRI were significantly improved at two weeks, 1, 3, and 6 months following radiofrequency (P-value < 0.001 in all comparisons). Statistically significant positive correlations were found between duration of pain, NRS, and S100B serum level before radiofrequency, and both NRS (P-value = 0.001, 0.035, < 0.001 respectively) and FRI (P-value = < 0.001, 0.009, 0.001 respectively) 6 months following radiofrequency. Whereas there were statistically significant negative correlations between BDNF serum level before radiofrequency and both NRS and FRI 6 months following radiofrequency (P-value = 0.022, 0.041 respectively). NRS and S100B serum levels before radiofrequency were found to be independent predictors of NRS 6 months following radiofrequency (P-value = 0.040. <0.001, respectively). CONCLUSION: Serum level of S100B is a promising biomarker that can predict functional outcomes after pulsed radiofrequency in patients with lumbar disc prolapse.
Subject(s)
Brain-Derived Neurotrophic Factor , Intervertebral Disc Displacement , Lumbar Vertebrae , Predictive Value of Tests , S100 Calcium Binding Protein beta Subunit , Humans , Brain-Derived Neurotrophic Factor/blood , Male , Female , Prospective Studies , S100 Calcium Binding Protein beta Subunit/blood , Middle Aged , Adult , Intervertebral Disc Displacement/blood , Intervertebral Disc Displacement/surgery , Treatment Outcome , Biomarkers/blood , Pain Measurement/methods , Pulsed Radiofrequency Treatment/methodsABSTRACT
S100 calcium-binding protein B (S100B) is a protein primarily known as a biomarker for central nervous system (CNS) injuries, reflecting blood-brain barrier (BBB) permeability and dysfunction. Recently, S100B has also been implicated in cardiovascular diseases, including heart failure (HF). Thus, we investigated serum levels of S100B in 146 chronic HF patients from the Cognition.Matters-HF study and their association with cardiac and cognitive dysfunction. The median S100B level was 33 pg/mL (IQR: 22-47 pg/mL). Higher S100B levels were linked to longer HF duration (p = 0.014) and increased left atrial volume index (p = 0.041), but also with a higher prevalence of mild cognitive impairment (p = 0.023) and lower visual/verbal memory scores (p = 0.006). In a multivariable model, NT-proBNP levels independently predicted S100B (T-value = 2.27, p = 0.026). S100B did not impact mortality (univariable HR (95% CI) 1.00 (0.99-1.01); p = 0.517; multivariable HR (95% CI) 1.01 (1.00-1.03); p = 0.142), likely due to its reflection of acute injury rather than long-term outcomes and the mild HF phenotype in our cohort. These findings underscore S100B's value in comprehensive disease assessment, reflecting both cardiac dysfunction and potentially related BBB disruption.
Subject(s)
Biomarkers , Cognitive Dysfunction , Heart Failure , S100 Calcium Binding Protein beta Subunit , Humans , S100 Calcium Binding Protein beta Subunit/blood , Heart Failure/blood , Male , Biomarkers/blood , Female , Cognitive Dysfunction/blood , Aged , Middle Aged , Chronic Disease , Natriuretic Peptide, Brain/blood , Peptide FragmentsABSTRACT
Permanent inflammatory demyelinating and neurodegenerative processes lead to neurological disability in patients with multiple sclerosis (MS). The anti-inflammatory properties of vitamin D3 (VitD) are well established, but its role in neurodegeneration is still uncertain. The usefulness of the serum concentration of VitD as a potential biomarker in evaluating brain injury in terms of recently known smoldering MS was under consideration. Methods: We assessed the concentrations of the parameters of brain injury (NF-H, GPAF, S100B, UCHL1) in the cerebrospinal fluid (CSF) of relapsing-remitting (RRMS, n = 123) and progressive MS (PMS, n = 88) patients in the group with normal levels of VitD (VitDn) and in the VitD deficiency group (VitDd). The levels of NF-H and UCHL1 were higher in the group of VitDd compared to VitDn. The higher serum levels of VitD were correlated with lower concentrations of GFAP, NF-H and S100B in the CSF of the whole group of MS patients and in women with MS as opposed to the levels of UCHL1. In men, there were noted negative correlations between the levels of serum VitD and GFAP and NF-H in CSF but not between VitD and S100B and UCHL1. The negative correlations were observed between VitD and the selected parameters of brain injury in MS patients, in women as well as in men. The concentrations of serum VitD together with selected parameters of brain injury in CSF seem to be promising biomarkers of neurodegeneration processes in smoldering MS.
Subject(s)
Biomarkers , Cholecalciferol , Multiple Sclerosis , S100 Calcium Binding Protein beta Subunit , Humans , Female , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Male , Middle Aged , Adult , Cholecalciferol/blood , S100 Calcium Binding Protein beta Subunit/blood , S100 Calcium Binding Protein beta Subunit/cerebrospinal fluid , Multiple Sclerosis/blood , Multiple Sclerosis/cerebrospinal fluid , Neurofilament Proteins/blood , Neurofilament Proteins/cerebrospinal fluid , Glial Fibrillary Acidic Protein/blood , Glial Fibrillary Acidic Protein/cerebrospinal fluid , Ubiquitin Thiolesterase/blood , Ubiquitin Thiolesterase/cerebrospinal fluid , Neurons/metabolism , Neurons/pathology , Aged , Multiple Sclerosis, Relapsing-Remitting/blood , Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid , Vitamin D Deficiency/blood , Vitamin D Deficiency/complicationsABSTRACT
INTRODUCTION: Sepsis-associated brain dysfunction is a common organ dysfunction in sepsis. The main goal of this study was to verify whether the combined assessment of central nervous system injury markers (i.e. S100B, NSE, GFAP) and disease severity as per the Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) classification systems, would increase the accuracy of death prediction in septic shock. MATERIAL AND METHODS: Markers of neuronal damage were determined in 55 patients diagnosed with septic shock with no previous neurological disease. Clinical data was collected and the scores on the APACHE II, SAPS II and SOFA prognostic scales were calculated. Death before discharge from the Intensive Care Unit (ICU) was established as the endpoint. RESULTS: Nineteen patients (35%) died before ICU discharge. Patients who died had significantly higher S100B and NSE values, and APACHE II, SAPS II and SOFA scores (P< 0.05 for all). At the time of septic shock diagnosis, NSE levels more accurately predicted the risk of death before ICU discharge than S100B. However, NSE had no better predictive value for short-term mortality than APACHE II, SAPS II and SOFA. Adding C-reactive protein (CRP) and S100B concentrations to the APACHE II score created a predictive model with 95% mortality accuracy (AUC = 0.95; 95%CI 0.85-0.99; P = 0.03). CONCLUSIONS: The assessment of acute neuronal injury plays an important role in prognostication in patients with septic shock. The concentration of S100B protein in combination with APACHE II score and concentration of CRP more accurately predicts mortality than the APACHE II alone.
Subject(s)
APACHE , S100 Calcium Binding Protein beta Subunit , Shock, Septic , Humans , Male , Female , Middle Aged , Prognosis , Shock, Septic/mortality , Poland , Aged , S100 Calcium Binding Protein beta Subunit/blood , Biomarkers/blood , Organ Dysfunction Scores , Critical Illness , Adult , Phosphopyruvate Hydratase/bloodABSTRACT
OBJECTIVES: To dynamically observe the changes in hypoxia-inducible factor 1α (HIF-1α) and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in children with traumatic brain injury (TBI) and evaluate their clinical value in predicting the severity and prognosis of pediatric TBI. METHODS: A prospective study included 47 children with moderate to severe TBI from January 2021 to July 2023, categorized into moderate (scores 9-12) and severe (scores 3-8) subgroups based on the Glasgow Coma Scale. A control group consisted of 30 children diagnosed and treated for inguinal hernia during the same period, with no underlying diseases. The levels of HIF-1α, BNIP3, autophagy-related protein Beclin-1, and S100B were compared among groups. The predictive value of HIF-1α, BNIP3, Beclin-1, and S100B for the severity and prognosis of TBI was assessed using receiver operating characteristic (ROC) curves. RESULTS: Serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in the TBI group were higher than those in the control group (P<0.05). Among the TBI patients, the severe subgroup had higher levels of HIF-1α, BNIP3, Beclin-1, and S100B than the moderate subgroup (P<0.05). Correlation analysis showed that the serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were negatively correlated with the Glasgow Coma Scale scores (P<0.05). After 7 days of treatment, serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in both non-surgical and surgical TBI patients decreased compared to before treatment (P<0.05). ROC curve analysis indicated that the areas under the curve for predicting severe TBI based on serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were 0.782, 0.835, 0.872, and 0.880, respectively (P<0.05), and for predicting poor prognosis of TBI were 0.749, 0.775, 0.814, and 0.751, respectively (P<0.05). CONCLUSIONS: Serum levels of HIF-1α, BNIP3, and Beclin-1 are significantly elevated in children with TBI, and their measurement can aid in the clinical assessment of the severity and prognosis of pediatric TBI.
Subject(s)
Beclin-1 , Brain Injuries, Traumatic , Hypoxia-Inducible Factor 1, alpha Subunit , Membrane Proteins , Humans , Male , Female , Brain Injuries, Traumatic/blood , Child , Membrane Proteins/blood , Child, Preschool , Hypoxia-Inducible Factor 1, alpha Subunit/blood , Beclin-1/blood , Prognosis , Proto-Oncogene Proteins/blood , S100 Calcium Binding Protein beta Subunit/blood , Prospective Studies , Infant , AdolescentABSTRACT
Circulating inflammatory markers are essential to human health and disease, and they are often dysregulated or malfunctioning in cancers as well as in cardiovascular, metabolic, immunologic and neuropsychiatric disorders. However, the genetic contribution to the physiological variation of levels of circulating inflammatory markers is largely unknown. Here we report the results of a genome-wide genetic study of blood concentration of ten cytokines, including the hitherto unexplored calcium-binding protein (S100B). The study leverages a unique sample of neonatal blood spots from 9,459 Danish subjects from the iPSYCH initiative. We estimate the SNP-heritability of marker levels as ranging from essentially zero for Erythropoietin (EPO) up to 73% for S100B. We identify and replicate 16 associated genomic regions (p < 5 x 10-9), of which four are novel. We show that the associated variants map to enhancer elements, suggesting a possible transcriptional effect of genomic variants on the cytokine levels. The identification of the genetic architecture underlying the basic levels of cytokines is likely to prompt studies investigating the relationship between cytokines and complex disease. Our results also suggest that the genetic architecture of cytokines is stable from neonatal to adult life.
Subject(s)
Cytokines/genetics , Inflammation/diagnosis , Quantitative Trait Loci , Biomarkers/blood , Cohort Studies , Cytokines/blood , Cytokines/immunology , Denmark , Enhancer Elements, Genetic/genetics , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Infant, Newborn , Inflammation/blood , Inflammation/immunology , Male , Polymorphism, Single Nucleotide , S100 Calcium Binding Protein beta Subunit/blood , S100 Calcium Binding Protein beta Subunit/genetics , S100 Calcium Binding Protein beta Subunit/immunologyABSTRACT
AIM: Antenatal corticosteroids (ACS) are recommended for women at risk of preterm birth before 34 weeks' gestation. However, adverse effects of ACS on the fetal brain have also been reported. The time interval from ACS administration to delivery (ACS-to-delivery interval) might alter the effect of ACS on the fetal brain. This study aimed to evaluate the effect of ACS-to-delivery interval on cord blood S100 calcium-binding protein B (S100B) levels as a biomarker of brain damage. METHODS: Women who delivered between 2012 and 2020 at a tertiary medical center were divided into three groups according to ACS use and ACS-to-delivery interval, retrospectively: non-ACS, ACS ≤7 days, and ACS >7 days. Patients who did not complete the ACS regimen were excluded. The primary outcome was cord blood S100B levels. RESULTS: Cord blood S100B levels were significantly lower in the ACS ≤7 days group than in the non-ACS and ACS >7 days groups. In the multiple regression analysis, birth ≤7 days after ACS showed a significant negative association with S100B level (p < 0.001). CONCLUSIONS: Reduced S100B levels were observed in infants born ≤7 days after ACS but not in infants born >7 days after ACS. These findings suggest the importance of ACS timing to optimize its effects on the fetal brain, although further studies are required to identify these mechanisms.
Subject(s)
Adrenal Cortex Hormones , Fetal Blood , Premature Birth , Female , Humans , Infant , Infant, Newborn , Pregnancy , Adrenal Cortex Hormones/adverse effects , Fetal Blood/metabolism , Gestational Age , Parturition , Retrospective Studies , S100 Calcium Binding Protein beta Subunit/bloodABSTRACT
OBJECTIVE: To evaluate the cerebral collateral circulation in patients with acute ischemic stroke (AIS) by Four-dimensional CT angiography-CT perfusion (4D CTA-CTP)-integrated technology, and to explore the feasibility of predicting the prognosis of patients with AIS by using cerebral collateral circulation and serum S100B protein concentration. METHODS: Thirty-two patients with anterior circulation AIS who underwent 4D CTA-CTP were retrospectively analysed. The level of cerebral collateral circulation was assessed by multi-phase CT angiography (mCTA) scores and regional leptomeningeal collateral (rLMC) scores. Combined with serum S100B protein concentration, multivariate binary logistic regression was used to explore the indicators that can independently predict the prognosis of AIS neurological function. RESULTS: Univariate analysis showed that the baseline National Institutes of Health stroke scale score, rLMC score, and mCTA score were correlated with the neurological prognosis of patients with AIS; multivariate analysis showed that mCTA cerebral collateral circulation score was the only indicator that could independently predict the neurological prognosis of AIS patients (ORâ¯=â¯0.065, Pâ¯=â¯0.030). The baseline serum S100B protein concentration could not independently predict the neurological prognosis of AIS patients. CONCLUSION: mCTA cerebral collateral circulation scores can independently predict the neurological prognosis of patients with AIS. For the assessment of neurological prognosis of AIS patients, the cerebral collateral circulation phase score is better than the regional score.
Subject(s)
Cerebral Angiography , Cerebrovascular Circulation , Collateral Circulation , Computed Tomography Angiography , Four-Dimensional Computed Tomography , Ischemic Stroke/blood , Ischemic Stroke/diagnostic imaging , Perfusion Imaging , S100 Calcium Binding Protein beta Subunit/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Disability Evaluation , Feasibility Studies , Female , Functional Status , Humans , Ischemic Stroke/physiopathology , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective StudiesABSTRACT
OBJECTIVE: To determine whether the presence of brain sparing in fetal growth restricted (FGR) fetuses involves elevation of the cerebral injury biomarker S100B in maternal circulation. METHODS: We included 63 women with suspected small for gestational age (SGA) fetuses between 24 and 35 +6/7 weeks of gestation. Maternal plasma angiogenic factors measurements and sonographic evaluation were performed at recruitment. Next, we subdivided our SGA cohort into three groups: SGA fetuses, FGR fetuses without brain-sparing, and FGR fetuses with brain-sparing (FGR-BS). Serum S100B concentration was calculated as S100B µg/L, S100B MoM, and the ratio S100B/ estimated fetal weight (EFW). We also report one case of S100B concentration surge in maternal serum following the diagnosis of fetal intraventricular hemorrhage (IVH). RESULTS: The FGR-BS group had higher maternal S100B µg/L (p < 0.01, p < 0.05, respectively), S100B MoM (p < 0.001, p < 0.001, respectively), and S100B/EFW (p < 0.001, p < 0.01, respectively), compared to the SGA and FGR groups. In the case report, maternal serum S100B concentrations were 0.0346 µg/L before, and 0.0874 µg/L after IVH occurrence. CONCLUSIONS: S100B concentration in maternal serum increased in pregnancies complicated by FGR and brain sparing. These results may substantiate in-utero cerebral injury and may explain the adverse neurocognitive outcomes reported for this group.
Subject(s)
Brain/abnormalities , Fetal Growth Retardation/diagnosis , Organ Sparing Treatments/methods , S100 Calcium Binding Protein beta Subunit/analysis , Adult , Brain/physiopathology , Female , Fetal Growth Retardation/physiopathology , Humans , Placental Circulation/genetics , Placental Circulation/physiology , Pregnancy , Prospective Studies , S100 Calcium Binding Protein beta Subunit/blood , Ultrasonography, Prenatal/methods , Ultrasonography, Prenatal/statistics & numerical dataABSTRACT
OBJECTIVE: S100B is a glial cell protein with bimodal function. In low concentrations, it exerts neurotrophic effects, but higher levels reflect neuronal distress. Recent research suggests that this molecule may be a biomarker of response to electroconvulsive therapy (ECT). We examined the effect of ECT on serum S100B and its utility as 1) a biomarker of a depressive state and 2) a predictor of ECT response. We also wanted to ensure that ECT does not cause a marked serum S100B elevation, indicating neural distress. METHODS: We measured serum S100B in 22 in-patients treated with ECT due to depression. Depression severity was assessed using 17-item Hamilton Rating Scale for Depression (HAMD-17). The data were collected before an ECT series, within 1 week after the series (post-ECT), and at a 6-month follow-up. Changes in serum S100B and clinical outcomes were tested using a linear mixed model. A relationship between serum S100B and the clinical outcomes was examined using Spearman's and partial correlation. RESULTS: Serum S100B did not change significantly immediately after an ECT series or 6 months later. The post-ECT serum S100B change was not associated with the clinical effect (rho = 0.14, n = 22, p = 0.54). The baseline serum S100B did not predict the clinical effect when controlling for age (r = 0.02, n = 22, df = 19, p = 0.92). CONCLUSION: The study neither supports serum S100B as a state marker of depression nor a predictor of ECT response. No evidence for ECT-related neural distress was found.
Subject(s)
Depression , Electroconvulsive Therapy , S100 Calcium Binding Protein beta Subunit , Humans , Biomarkers/blood , Depression/therapy , S100 Calcium Binding Protein beta Subunit/blood , Treatment OutcomeABSTRACT
BACKGROUND: Post-stroke anxiety (PSA) is a common neuropsychiatric affective disorder occurring after a stroke. Animal experiments have indicated that serum S-100ß levels are closely related to anxiety disorder. No clinical study has been done to explore the relationship between serum S-100ß levels and anxiety symptoms in patients with acute stroke. The aim of our study was to investigate the association between serum S-100ß levels and PSA. METHODS: One hundred twenty-six acute stroke patients were recruited and followed up for 1 month. Blood samples were collected within 24 h after admission. The levels of serum S-100ß were measured by enzyme-linked immunosorbent assays. Patients with significant clinical symptoms of anxiety and a Hamilton Anxiety Rating Scale score >7 at 1 month after stroke were diagnosed as PSA. RESULTS: Serum S-100ß levels in the non-PSA group were lower than the PSA group (838.97 (678.20-993.59) ng/L vs. 961.87 (796.09-1479.59) ng/L, Z = -2.661, P = 0.008). In multivariate analyses, we found that decreased risk of PSA was associated with low tertile serum S-100ß levels (≤753.8 ng/L, OR 0.062, 95% CI 0.008-0.475, P = 0.007). CONCLUSIONS: Low serum S-100ß levels at admission may be associated with the decreased risk of PSA.
Subject(s)
Prostate-Specific Antigen , S100 Calcium Binding Protein beta Subunit/blood , Stroke , Animals , Anxiety , Biomarkers , Humans , Male , Multivariate Analysis , Stroke/complications , Stroke/psychologyABSTRACT
Ischemic stroke is the main cause of permanent disability in adult patients. No commonly accepted method were discovered to predict stroke before the first symptoms. Activation of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMP) and S100B protein may be observe in patients with symptomatic carotid artery stenosis. Hemorrhagic transformation of ischemic stroke may be associated with changes in MMP, TIMP and S100B. AIM: The aim of this study was to determine if MMP-9, TIMP-1 and S-100B protein may markers of forthcoming ischemic stroke in patients undergoing carotid endarterectomy. MATERIALS AND METHODS: Blood samples were taken and an analysis of circulating proteins (MMP-9, TIMP-1, S100B) 73 subsequent patients with carotid artery stenosis ≥70% (33 asymptomatic and 40 symptomatic), who were referred for potential revascularization. RESULTS: A statistically significant difference was found between MMP- 9 levels in patients with ischemic stroke compared to patients with asymptomatic carotid stenosis after endarterectomy. Also, average TIMP-1 levels in patients with ischemic stroke and stenosis ≥70% were statistically significantly higher than the average levels in patients after endarterectomy. In terms of S-100B, a higher mean value was observed in patients with stroke than in endarterectomy group. No statistical differences were found in the levels of that proteins in the hemorrhagic transformation of ischemic stroke. CONCLUSIONS: Increased levels of MMP-9, TIMP-1 and S-100B in patients with ischemic stroke compared to patients with asymptomatic carotid stenosis after endarterectomy showed that abovementioned proteins may be a good predictive factor of ischemic stroke in patients undergoing carotid endarterectomy.
Subject(s)
Carotid Stenosis , Endarterectomy, Carotid , Ischemic Stroke , Adult , Biomarkers/blood , Carotid Arteries , Carotid Stenosis/complications , Carotid Stenosis/surgery , Endarterectomy, Carotid/adverse effects , Humans , Ischemic Stroke/diagnosis , Ischemic Stroke/etiology , Matrix Metalloproteinase 9/blood , S100 Calcium Binding Protein beta Subunit/blood , Tissue Inhibitor of Metalloproteinase-1/bloodABSTRACT
Acute methadone toxicity is a major public health concern which has adverse effects on brain tissue and results in recurrent or delayed respiratory arrest. Our study aimed to investigate the time-dependent changes in several serum biochemical markers of brain damage, spatial working memory, and the brain tissue following acute methadone overdose. Adolescent male rats underwent an intraperitoneal (i.p.) injection of 15 mg/kg methadone. In case of apnea occurrence, resuscitation was performed by a ventilatory pump and administrating naloxone (2 mg/kg; i.p.). The animals were classified into groups of treated rats; methadone and naloxone-Apnea (M/N-Apnea), M/N-Sedate, Methadone, Naloxone, and control (saline) groups. The serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein factors, and (Lactate/Pyruvate) L/P ratio were evaluated at the time-points of 6, 24, and 48 h (h). We found that the alterations of S100B and L/P ratio were considerable in the M/N-Apnea and Methadone groups from the early hours post-methadone overdose, while NSE serum levels elevation was observed only in M/N-Apnea group with a delay at 48 h. Further, we assessed the spatial working memory (Y-maze test), morphological changes, and neuronal loss. The impaired spontaneous alternation behavior was detected in the M/N-Apnea groups on days 5 and 10 post-methadone overdose. The morphological changes of neurons and the neuronal loss were detectable in the CA1, striatum, and cerebellum regions, which were pronounced in both M/N-Apnea and Methadone groups. Together, our findings suggest that alterations in the serum levels of S100B and NSE factors as well as L/P ratio could be induced by methadone overdose with the presence or absence of apnea before the memory impairment and tissue injury in adolescent male rats.