Longitudinal Analysis of Antibody Response Following SARS-CoV-2 Infection Depending on Disease Severity: A Prospective Cohort Study.

OBJECTIVE: Severe coronavirus disease 19 (COVID-19) is characterized by a dysregulated inflammatory response, with humoral immunity playing a central role in the disease course. The objective of this study was to assess the immune response and the effects of vaccination in recovered individuals with variable disease severity up to one year following natural infection. METHODS: A prospective cohort study was conducted including patients with laboratory-confirmed COVID-19. Disease severity was classified as mild, moderate, and severe based on clinical presentation and outcomes. Anti-RBD (receptor binding domain) and neutralizing antibodies were evaluated at multiple timepoints during the first year after COVID-19 diagnosis. RESULTS: A total of 106 patients were included; of them, 28 were diagnosed with mild, 38 with moderate, and 40 with severe disease. At least one vaccine dose was administered in 58 individuals during the follow-up. Participants with mild disease presented significantly lower anti-RBD and neutralizing antibodies compared to those with moderate and severe disease up to the 3rd and 6th months after the infection, respectively. After adjusting for covariates, in the third month, severe COVID-19 was associated with significantly higher anti-RBD (ß: 563.09; 95% confidence intervals (CI): 257.02 to 869.17) and neutralizing (ß: 21.47; 95% CI: 12.04 to 30.90) antibodies. Among vaccinated individuals, at the 12th month, a history of moderate disease was associated with significantly higher anti-RBD levels (ß: 5615.19; 95% CI: 657.92 to 10,572.46). CONCLUSIONS: Severe COVID-19 is associated with higher anti-RBD and neutralizing antibodies up to 6 months after the infection. Vaccination of recovered patients is associated with a remarkable augmentation of antibody titers up to one year after COVID-19 diagnosis, regardless of disease severity.

Immune response and adverse events after vaccination against SARS-CoV-2 in adult patients with transfusion-dependent thalassaemia.

Patients with transfusion-dependent thalassaemia (TDT) are considered an at increased-risk population for severe and/or morbid coronavirus disease 2019 (COVID-19) infection. Timely vaccination is the main preventive method for severe COVID-19. Different adverse events and reactions after vaccination have been reported, with severe ones being extremely rare. Patients with TDT may have altered immunity due to chronic transfusions, iron overload and chelation therapy, and splenic dysfunction. Here, we show that adult patients with TDT following vaccination with the novel messenger RNA vaccines have mild adverse events and can produce protective antibodies comparable to the healthy population.

Sustained but Declining Humoral Immunity Against SARS-CoV-2 at 9 Months Postvaccination With BNT162b2: A Prospective Evaluation in 309 Healthy Individuals.

The sustainability of coronavirus 19 (COVID-19) vaccine-induced immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to be determined to inform public health decisions on vaccination programs and prevention measures against COVID-19. The aim of the present study was to prospectively evaluate the kinetics of neutralizing antibodies (NAbs) and anti-S-receptor binding domain (RBD IgGs) against SARS-CoV-2 after full vaccination with the BNT162b2 mRNA vaccine for up to 9 months in healthy individuals (NCT04743388). The assessments were performed at the following time points after the second vaccination: 2 weeks, 1 month, 3 months, 6 months, and 9 months. The measurements were performed with the GenScript's cPassTM SARS-CoV-2 NAbs Detection Kit (GenScript, Inc.; Piscataway, NJ) and the Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics GmbH; Mannheim, Germany). Three hundred nine participants with a median age of 48 years were included. A gradual decline in both NAbs and anti-S-RBD IgGs became evident from 2 weeks to 9 months postvaccination. Both NAbs and anti-S-RBD IgGs levels were significantly lower at 9 months compared with the previous timepoints. Interestingly, age was found to exert a statistically significant effect on NAbs elimination only during the first-trimester postvaccination, as older age was associated with a more rapid clearance of NAbs. Furthermore, simulation studies predicted that the median NAb value would fall from 66% at 9 months to 59% and 45% at 12 and 18 months postvaccination, respectively. This finding may reflect a declining degree of immune protection against COVID-19 and advocates for the administration of booster vaccine shots especially in areas with emerging outbreaks.

Systemic IL-15, IFN-γ, and IP-10/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients.

Early responses to vaccination are important for shaping both humoral and cellular protective immunity. Dissecting innate vaccine signatures may predict immunogenicity to help optimize the efficacy of mRNA and other vaccine strategies. Here, we characterize the cytokine and chemokine responses to the 1st and 2nd dose of the BNT162b2 mRNA (Pfizer/BioNtech) vaccine in antigen-naive and in previously coronavirus disease 2019 (COVID-19)-infected individuals (NCT04743388). Transient increases in interleukin-15 (IL-15) and interferon gamma (IFN-γ) levels early after boost correlate with Spike antibody levels, supporting their use as biomarkers of effective humoral immunity development in response to vaccination. We identify a systemic signature including increases in IL-15, IFN-γ, and IP-10/CXCL10 after the 1st vaccination, which were enriched by tumor necrosis factor alpha (TNF-α) and IL-6 after the 2nd vaccination. In previously COVID-19-infected individuals, a single vaccination results in both strong cytokine induction and antibody titers similar to the ones observed upon booster vaccination in antigen-naive individuals, a result with potential implication for future public health recommendations.

Comparative kinetics of SARS-CoV-2 anti-spike protein RBD IgGs and neutralizing antibodies in convalescent and naïve recipients of the BNT162b2 mRNA vaccine versus COVID-19 patients.

BACKGROUND: Coronavirus SARS-CoV-2, the causative agent of COVID-19, has caused a still evolving global pandemic. Given the worldwide vaccination campaign, the understanding of the vaccine-induced versus COVID-19-induced immunity will contribute to adjusting vaccine dosing strategies and speeding-up vaccination efforts. METHODS: Anti-spike-RBD IgGs and neutralizing antibodies (NAbs) titers were measured in BNT162b2 mRNA vaccinated participants (n = 250); we also investigated humoral and cellular immune responses in vaccinated individuals (n = 21) of this cohort 5 months post-vaccination and assayed NAbs levels in COVID-19 hospitalized patients (n = 60) with moderate or severe disease, as well as in COVID-19 recovered patients (n = 34). RESULTS: We found that one (boosting) dose of the BNT162b2 vaccine triggers robust immune (i.e., anti-spike-RBD IgGs and NAbs) responses in COVID-19 convalescent healthy recipients, while naïve recipients require both priming and boosting shots to acquire high antibody titers. Severe COVID-19 triggers an earlier and more intense (versus moderate disease) immune response in hospitalized patients; in all cases, however, antibody titers remain at high levels in COVID-19 recovered patients. Although virus infection promotes an earlier and more intense, versus priming vaccination, immune response, boosting vaccination induces antibody titers significantly higher and likely more durable versus COVID-19. In support, high anti-spike-RBD IgGs/NAbs titers along with spike (vaccine encoded antigen) specific T cell clones were found in the serum and peripheral blood mononuclear cells, respectively, of vaccinated individuals 5 months post-vaccination. CONCLUSIONS: These findings support vaccination efficacy, also suggesting that vaccination likely offers more protection than natural infection.

Kinetics of Anti-SARS-CoV-2 Antibody Responses 3 Months Post Complete Vaccination with BNT162b2; A Prospective Study in 283 Health Workers.

The aim of this study was to investigate the kinetics of neutralizing antibodies (NAbs) and anti-SARS-CoV-2 anti-S-RBD IgGs up to three months after the second vaccination dose with the BNT162b2 mRNA vaccine. NAbs and anti-S-RBD levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and three months after the second vaccination (D111) (NCT04743388). 283 health workers were included in this study. NAbs showed a rapid increase from D8 to D36 at a constant rate of about 3% per day and reached a median (SD) of 97.2% (4.7) at D36. From D36 to D50, a slight decrease in NAbs values was detected and it became more prominent between D50 and D111 when the rate of decline was determined at -0.11 per day. The median (SD) NAbs value at D111 was 92.7% (11.8). A similar pattern was also observed for anti-S-RBD antibodies. Anti-S-RBDs showed a steeper increase during D22-D36 and a lower decline rate during D36-D111. Prior COVID-19 infection and younger age were associated with superior antibody responses over time. In conclusion, we found a persistent but declining anti-SARS-CoV-2 humoral immunity at 3 months following full vaccination with BNT162b2 in healthy individuals.

Increased Serum Concentrations of High Mobility Group Box 1 (HMGB1) Protein in Children with Autism Spectrum Disorder.

High mobility group box 1 protein (HMGB1) has been suggested to be involved in the immune dysfunction and inflammation reported in autism spectrum disorder (ASD). We aimed to assess HMGB1 serum concentrations (SCs) in high-functioning ASD children compared to typically developing (TD) controls and to explore their associations with the autism spectrum quotient (AQ), the empathy quotient (EQ), and the systemizing quotient (SQ). The study involved 42 ASD children and 38 TD children, all-male, aged between 6.1 and 13.3 years old. HMGB1 SCs were measured by enzyme-linked immunosorbent assay (ELISA). Groups were comparable regarding age, general IQ, birth weight, and maternal age at birth. ASD children showed significantly higher HMGB1 SCs compared to TD children (1.25 ± 0.84 ng/mL versus 1.13 ± 0.79 ng/mL, respectively, p = 0.039). The Spearman's rho revealed that HMGB1 SCs were positively correlated with the AQ attention to detail subscale (rs = 0.46, p = 0.045) and with the SQ total score (rs = 0.42, p = 0.04) in the ASD group. These results show that HMGB1 serum concentrations are altered in ASD children, and suggest that inflammatory processes mediated by HMGB1 may be associated with specific cognitive features observed in ASD.

Salivary cortisol and alpha-amylase daily profiles and stress responses to an academic performance test and a moral cognition task in children with neurodevelopmental disorders.

There is evidence that children with neurodevelopmental disorders may exhibit atypical responses to stress and alterations in concentrations and diurnal secretion of stress hormones. We assessed diurnal profiles and stress responses of salivary cortisol and alpha-amylase (sAA) in children with attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and specific learning disorder (SLD) compared to typically developing children (TD). A total of 157 children of both sexes, aged between 6 and 12 years old, took part in the study distributed into four groups: ADHD (N = 34), ASD (N = 56), SLD (N = 43) and TD (N = 24). Salivary samples were collected at three time points during a day, as well as before and 5 min after an academic performance test and a moral cognition task. ADHD children had lower evening and diurnal sAA levels, adjusted for age. Also, ASD children showed lower diurnal sAA secretion, adjusted for age. The mean percentage change for salivary cortisol and sAA after both tests did not differ between the groups. In conclusion, we demonstrated alterations in diurnal autonomic functioning in children with ADHD and ASD, while hypothalamic-pituitary-adrenal axis functioning did not differ between the clinical and the comparison groups.

Only vulnerable adults show change in chronic low-grade inflammation after contemplative mental training: evidence from a randomized clinical trial.

Growing evidence suggests that chronic low-grade inflammation can be reduced through mindfulness-based mental training interventions. However, these results are inconsistent and based on patient populations with heterogeneous conditions. Similar research in healthy adults is lacking. Moreover, common intervention protocols involve varying combinations of different contemplative practices, such that it remains unclear which types of training most effectively influence biomarkers of inflammation. The present study investigated the effect of three distinct 3-month training modules cultivating a) interoception and present-moment focus (Presence), b) socio-affective skills (Affect), or c) socio-cognitive skills (Perspective) on the inflammatory biomarkers interleukin-6 (IL-6) and high sensitive C-reactive protein (hs-CRP) in 298 healthy adults. We observed no group-level effect of training on either biomarker, but trend-level interactions of training type and participant sex. In additionally exploring the influence of participants' baseline inflammation, a selective training effect emerged: Following the Presence module, participants with relatively higher inflammatory load showed stronger reduction in IL-6 on average, and in hs-CRP if they were male. Mindfulness- and attention-based mental practice thus appears most effective when targeting chronic low-grade inflammation in healthy adults, particularly in men. Overall, our data point to a floor effect in the reduction of inflammatory markers through contemplative mental training, suggesting that mental training may be less effective in improving basal biological health outcomes in healthy, low-stressed adults than in vulnerable populations.

Salivary biomarkers may measure stress responses in critically ill children.

OBJECTIVE: Measurement of salivary biomarkers can provide important information regarding hypothalamic-pituitary-adrenal axis activity both under normal conditions as well as in response to psychological or physical stress. Our aim was to correlate salivary stress markers, such as cortisol, α-amylase and immunoglobulin A, with the Pediatric Risk Index Score of Mortality, underlying disease (pathologic, trauma and postoperative), need for mechanical ventilation/sedation and time lag between onset of illness and admission in children admitted in the pediatric intensive care unit. METHODS: We enrolled 79 pediatric intensive care unit patients (2-14 years) over a 2-year period, which satisfy the including criteria, but finally salivary biomarkers were evaluated in 65 patients. Saliva samples were collected within 24 h of admission at 8 a.m., 2 p.m. and 8 p.m. to examine potential disruption of circadian rhythm. RESULTS: Overall, the salivary biomarkers were increased; specifically, median values were (a) cortisol at 8 a.m.: 50.04 nmol/L, 2 p.m.: 30.69 nmol/L and 8 p.m.: 247.12 nmol/L; (b) α-amylase: at 8 a.m.: 22.567 U/L; 2 p.m.: 22.702 U/L and 8 p.m.: 21.484 U/L and (c) IgA at 8 a.m.: 95.10 mg/dL, 2 p.m.: 88.55 mg/dL and 8 p.m.: 80.80 mg/dL. Significantly higher levels were demonstrated in children younger than 6 years and those with Pediatric Risk Index Score of Mortality ⩾8 upon admission. Disturbances in circadian rhythm were observed. Cortisol circadian rhythm disturbance was observed only in children with Pediatric Risk Index Score of Mortality score ⩾8 upon admission while maintaining normal α-amylase circadian rhythm, which was associated with less than 3 days hospitalization in pediatric intensive care unit. No daily variance in IgA was observed. CONCLUSION: Salivary biomarkers may serve, in critically ill children, as a sensitive, non-invasive method, important for the early recognition of those at high risk and guiding intervention, before clinical deterioration, promoting the quality of health care in pediatric population.

Exploring the multidimensional complex systems structure of the stress response and its relation to health and sleep outcomes.

To gain a comprehensive understanding of the multidimensional complex systems structure of the stress response and related health outcomes, we utilized network analysis in a sample of 328 healthy participants in two steps. In a first step, we focused on associations between measures of basal hypothalamic-pituitary-adrenal axis functioning and subjective stress perceptions. In a second step, we linked these diverse stress-related measures to biomarkers and self-reports of health and sleep. Overall, measures clustered depending on their method of assessment, with high correlations between different saliva-based indices of diurnal cortisol regulation, between cortisol and cortisone levels in hair, between different biological health indicators (systemic inflammatory activity and body mass index), between state (experience sampling) and trait (questionnaire-based) self-reports of stress and wellbeing, and between different self-reports of sleep. Bridges between clusters suggested that if individuals perceive stress throughout their daily lives this is reflected in their total salivary cortisol output possibly contributing to long-term cortisol accumulation in hair. Likewise, earlier awakening time may contribute to cortisol accumulation in hair via an influence on awakening cortisol processes. Our results show that while meaningful connections between measures exist, stress is a highly complex construct composed of numerous aspects. We argue that network analysis is an integrative statistical approach to address the multidimensionality of the stress response and its effects on the brain and body. This may help uncover pathways to stress-related disease and serve to identify starting points for prevention and therapeutic intervention.

PlGF and sFlt-1 levels in patients with non-transfusion-dependent thalassemia: Correlations with markers of iron burden and endothelial dysfunction.

BACKGROUND: Levels of the angiogenic cytokines placental growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFlt-1) and the angiogenic balance, expressed by sFlt-1/PlGF ratio, are perturbed in sickle-cell disease and iron overload, but they have not been evaluated in non-transfusion-dependent thalassemia (NTDT). PATIENTS AND METHODS: We measured levels of PlGF, sFlt-1 and vWF:antigen in patients with NTDT of beta-thalassemia genotype, and correlated them with erythrocytic indices and markers of iron overload, inflammation, and tissue hypoxia. Thirty-four NTDT patients with mean hemoglobin level of 8.4 g/dL were included in the study along with 20 apparently healthy individuals who served as controls. RESULTS: Ferritin, LDH, and hs-CRP were higher in patients as compared to controls. We found significant differences between patients and controls in regard to levels of PlGF (52.2 vs 17.2 pg/mL, P < .001), sFlt-1/PlGF (2 vs 4.7, P < .001), and vWF:antigen (88 vs 77.1 IU/dL, P < .01). There was a strong correlation of ferritin with PlGF (r = .653, P < .001) and with vWF:antigen (r = .503, P = .003). CONCLUSIONS: In this study, we demonstrated an association between increased PlGF and iron overload and the degree of tissue hypoxia in patients with NTDT. High vWF:antigen expressing endothelial damage may be associated with specific NTDT comorbidities.

Salivary cortisol and alpha-amylase diurnal profiles and stress reactivity in children with Attention Deficit Hyperactivity Disorder.

There is growing evidence for dysregulation of the stress system in individuals with Attention Deficit Hyperactivity Disorder (ADHD). The stress system includes neuroanatomical and functional components that function in concert to maintain homeostasis and its main effectors are the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic/adrenomedullary nervous system (SNS). As stress system activity demonstrates a distinct circadian variation, we aimed to describe simultaneously, diurnal rhythms of both the HPA axis and the SNS in children with ADHD and a comparison group. Moreover, we attempted to investigate stress responses to a physical stressor, venipuncture, in both groups. Sixty-two prepubertal children with ADHD combined (ADHD-C) or inattentive (ADHD-I) type and 40 typically developing children provided saliva samples at six specific time points during a day, as well as before and 10 min after a scheduled morning venipuncture. Salivary cortisol and α- amylase were selected as reliable noninvasive biomarkers for HPA axis and SNS function and were measured in the samples obtained. Results revealed that children with ADHD-C had lower mean cortisol values both 30 min after awakening and at 18:00 h than controls (p = 0.002 and p = 0.018 respectively), as well as lower mean Cortisol Awakening Response (CAR) and Area Under the Curve for "wake to bed" period (AUCi) values of cortisol (p = 0.004 and p = 0.001, respectively). Also, mean CAR and cortisol AUCi were lower in children with ADHD-I than the control group (p = 0.034 and p = 0.038 respectively). Alpha-amylase measurements showed an increase over time (p < 0.001), which was similar in all three groups. Interestingly, α-amylase changes over time were correlated with the corresponding cortisol changes (p < 0.001). Venipuncture, elicited a significant increase only in α-amylase levels and more so in the control group (p = 0.003). These findings suggest a partial hypofunction of the stress system in children with ADHD.

Growth differentiation factor-15 is a new biomarker for survival and renal outcomes in light chain amyloidosis.

Growth differentiation factor-15 (GDF-15) improves prognostication in patients with cardiovascular disorders in addition to conventional cardiac markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], troponins [Tns]) and has shown prognostic value in patients with renal diseases. In patients with light chain (AL) amyloidosis, cardiac involvement is the major determinant of prognosis, and cardiac markers define prognosis, whereas biomarkers of renal involvement stratify renal risk. We explored the prognostic importance of serum level of GDF-15 in patients with AL amyloidosis in 2 independent cohorts. The prognostic value of GDF-15 level was initially evaluated in a cohort of 107 consecutive previously untreated patients with AL amyloidosis from Athens, Greece, and was then validated in a second cohort of 202 consecutive previously untreated patients from Pavia, Italy. High GDF-15 level was associated with a higher risk of early death and poor overall survival independently of NT-proBNP and high-sensitivity TnT (hsTnT) or hsTnI levels. At the 6-month landmark, reduction of GDF-15 level ≥25% was associated with improved outcome. GDF-15 level ≥4000 pg/mL was associated with a high risk of progression to dialysis, independently of renal risk defined by estimated glomerular filtration rate and proteinuria, in both cohorts; failure to reduce GDF-15 below this level was associated with increased risk at either the 3- or 6-month landmark, independently of the established renal response or progression criteria. In conclusion, GDF-15 has prognostic implications for different outcomes in patients with AL and adds prognostic information independent of that provided by cardiac and renal risk biomarkers.

Mothers' parenting stress is associated with salivary cortisol profiles in children with attention deficit hyperactivity disorder.

The aim of this study was to explore the relation between mothers' parenting stress and the functioning of the hypothalamic-pituitary-adrenal axis (HPAA), as expressed by daily salivary cortisol concentrations, in their children diagnosed with attention deficit hyperactivity disorder (ADHD). Seventy-five children aged 6-11 years diagnosed with ADHD predominant hyperactive-impulsive/combined (ADHD-HI/C, N = 49) and inattentive symptoms (ADHD-I, N = 26) and 45 healthy peers and their mothers participated in the study. Μothers completed measures assessing their children's ADHD status, perceived parenting stress (Parenting Stress Index - Short Form, PSI-SF), mothers' symptoms of psychopathology, social support and socioeconomic status. Children's salivary cortisol samples were collected at six different time points on a single day. Mothers of children with ADHD-HI/C reported higher levels of parenting stress than mothers of children with ADHD-I and controls. All PSI-SF subscales showed significant associations with children's cortisol awakening response (CAR) in both ADHD groups, with the exception of the parental distress subscale in the ADHD-I group. In both ADHD groups, the parent-child dysfunctional interaction subscale, the difficult child subscale and the PSI total score were significantly associated with children's CAR. An interrelation is revealed between mothers' high levels of parenting stress and HPAA functioning in children with ADHD. In this population, CAR has been identified as a sensitive peripheral measure of HPAA functioning in children. Lay summaryThis study showed that in families of children diagnosed with ADHD, there is a complex relation between the mothers' high levels of parenting stress and children's atypical hypothalamic-pituitary-adrenal axis functioning.

Hair cortisol concentrations exhibit a positive association with salivary cortisol profiles and are increased in obese prepubertal girls.

Cortisol, a key mediator of the stress response, has been associated with obesity and metabolic syndrome manifestations as early as in childhood. Scalp hair cortisol has been proposed as a reliable index of long-term circulating cortisol. We aimed to investigate whether obese prepubertal girls have higher scalp hair cortisol than normal-weight controls and whether hair cortisol levels are correlated with salivary cortisol concentrations in these groups. In this cross-sectional study, 25 obese girls and 25 normal-weighted, age-matched girls were enrolled. Anthropometric evaluation, blood chemistry and salivary cortisol measurements were performed, and body mass index (BMI) and areas under the curve with respect to ground (AUCg) were calculated. Hair cortisol determination was performed with liquid chromatography-tandem mass spectrometry. Both hair cortisol concentrations and salivary cortisol AUCs were higher in the obese than the normal-weight girls (p < .001 and p = .002, respectively). A positive correlation between hair cortisol and BMI Z-score was found (rho = .327, p = .025), while hair cortisol correlated positively with salivary cortisol AUCg (rho = .3, p = .048). We conclude that obese prepubertal girls have higher hair and salivary cortisol concentrations than their age-matched lean counterparts. Hair cortisol assessment seems to be a sensitive method of evaluating systemic cortisol exposure, which is supported by our finding that hair cortisol is associated with salivary concentrations of the hormone. Lay Summary: Cortisol is the key hormone of the stress response. Childhood obesity has been associated with cortisol production dysregulation. Our findings suggest a positive association between obesity in prepubertal girls and elevated cortisol concentrations, measured in saliva and hair.

Increased placental growth factor (PlGF) concentrations in children and adolescents with obesity and the metabolic syndrome.

OBJECTIVE: Childhood obesity and the Metabolic Syndrome (MetS) are associated with an increased risk for early onset endothelial dysfunction and atherosclerosis. Placental growth factor (PlGF), a member of the vascular endothelial growth factor family, plays an important role in atherosclerosis by stimulating angiogenesis and atherogenic migration of monocytes/macrophages into the arterial wall. The aim of this study was to investigate differences in circulating PlGF concentrations between children with obesity/metabolic syndrome and non-obese children. We have previously shown increased high-sensitivity troponin (hs-TnT) concentrations in children with MetS from the same cohort. DESIGN: Fifty-seven obese (49 without and 8 with MetS) and 25 non-obese children (controls) were assessed at the Childhood Obesity Clinic of our Department. Obesity was defined using the IOTF criteria. MetS was defined based on the IDF criteria. PlGF was measured using electrochemiluminescence methodology. RESULTS: Mean PIGF concentrations of obese children were significantly higher (p=0.048) compared with those of the controls. Analysis of the three groups, the οbese (without MetS), the MetS and the control, demonstrated a significant difference in PlGF concentrations (p=0.035). Subgroup analysis revealed increased PlGF concentrations in children with the MetS compared to the controls (p=0.009). Troponin had a significant positive correlation with PlGF overall (p=0.003) and in the obese group (p=0.046). CONCLUSIONS: Increased serum concentrations of PlGF, a biomarker of angiogenesis, are found in obese children with the MetS compared to non-obese controls, whereas PlGF correlated positively with troponin. Longitudinal studies may reveal the prognostic role of this biomarker in the progression of atherosclerosis in obese children with the MetS.

Increased circulating High-Sensitivity Troponin T concentrations in children and adolescents with obesity and the metabolic syndrome: a marker for early cardiac damage?

OBJECTIVE: Childhood obesity is associated with an increased risk for atherosclerosis mediated by the pathogenetic mechanisms that lead to the development of the Metabolic Syndrome (MetS). High-Sensitivity Troponin T (hs-TnT) is a specific marker of ischemic myocardial damage, whereas a minimal elevation of this biomarker has been found in adults with a high-risk for cardiovascular disease. We hypothesized that hs-TnT might be altered in obese children with and/or without the Mets. MATERIALS AND METHODS: Fifty-seven (34 males) obese and 25 non-obese (6 males) children were assessed at the Childhood Obesity Clinic of our department. Obesity was defined using the IOTF criteria. Metabolic syndrome was defined with the IDF criteria. Hs-TnT was measured using an electrochemiluminescence-based assay. RESULTS: The entire group of obese children had significantly higher hs-TnT concentrations [4.1 ± 3.4 ng/L] (p=0.029) than the non-obese ones [3.0 ± 0.2 ng/L), however, in both groups the levels of the cardiac biomarker were within the normal range. Comparison of the obese children with or without the MetS and the non-obese, revealed that those with the MetS had significantly higher hs-TnT (6.7±7.1 ng/L) than the obese without MetS (3.7 ± 2.1 ng/L) [p=0.044], and the non-obese [p=0.014]. Hs-TnT did not differ between the obese without MetS and the non-obese. CONCLUSIONS: Circulating concentrations of hs-TnT in obese children with the MetS are higher than those of the obese without the MetS and the non-obese, suggesting that it is obesity-related metabolic changes rather than obesity per se linked to increased hs-TnT in children.