Association between Neonatal Whole Blood Iron Content and Cytokines, Adipokines, and Other Immune Response Proteins.
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ABSTRACT:
SUBMITTER: Thorsen SU
PROVIDER: S-EPMC6470999 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:(1) Background: Zinc is an essential micronutrient and zinc deficiency is associated with immune dysfunction. The neonatal immune system is immature, and therefore an optimal neonatal zinc status may be important. The aim of this study was to investigate the possible association between neonatal whole blood (WB)-Zinc content and several immune markers. (2) Methods: In total, 398 healthy newborns (199 who later developed type 1 diabetes and 199 controls) from the Danish Newborn Screening Biobank had neonatal dried blood spots (NDBS) analyzed for WB-Zinc content and (i) cytokines: Interleukin (IL)-1?, IL-4, IL-6, IL-8, IL-10, IL-12 (p70), interferon gamma, tumor necrosis factor alpha, and transforming growth factor beta; (ii) adipokines: leptin and adiponectin; (iii) other immune response proteins: C-reactive protein (CRP), and mannose-binding lectin (MBL), and soluble triggering receptors expressed on myeloid cells1 (sTREM-1). WB-Zinc content was determined using laser ablation inductively coupled plasma mass spectrometry. For each analyte, the relative change in mean level was modelled by a robust log-normal model regression. (3) Results: No association was found between WB-Zinc content and all the immune response markers in either the unadjusted or adjusted models overall or when stratifying by case status. (4) Conclusions: In healthy Danish neonates, WB-Zinc content was not associated with cytokines, adipokines, CRP, MBL or sTREM, which does not indicate a strong immunological function of neonatal zinc status.
| S-EPMC6769600 | biostudies-literature
Project description:BackgroundCord blood leptin and adiponectin are adipokines known to be associated with birth weight and overall infant adiposity. However, few studies have investigated their associations with abdominal adiposity in neonates. We examined maternal factors associated with cord blood leptin and adiponectin, and the association of these adipokines with neonatal adiposity and abdominal fat distribution measured by magnetic resonance imaging (MRI) in an Asian mother-offspring cohort.MethodsGrowing Up in Singapore Towards healthy Outcomes (GUSTO), is a prospective mother-offspring birth cohort study in Singapore. Cord blood plasma leptin and adiponectin concentrations were measured using Luminex and Enzyme-Linked Immunosorbent Assay respectively in 816 infants. A total of 271 neonates underwent MRI within the first 2-weeks after delivery. Abdominal superficial (sSAT), deep subcutaneous (dSAT), and intra-abdominal (IAT) adipose tissue compartment volumes were quantified from MRI images. Multivariable regression analyses were performed.ResultsIndian or Malay ethnicity, female sex, and gestational age were positively associated with cord blood leptin and adiponectin concentrations. Maternal gestational diabetes (GDM) positively associated with cord blood leptin concentrations but inversely associated with cord blood adiponectin concentrations. Maternal pre-pregnancy body mass index (BMI) showed a positive relationship with cord blood leptin but not with adiponectin concentrations. Each SD increase in cord blood leptin was associated with higher neonatal sSAT, dSAT and IAT; differences in SD (95% CI): 0.258 (0.142, 0.374), 0.386 (0.254, 0.517) and 0.250 (0.118, 0.383), respectively. Similarly, each SD increase in cord blood adiponectin was associated with higher neonatal sSAT and dSAT; differences in SD (95% CI): 0.185 (0.096, 0.274) and 0.173 (0.067, 0.278), respectively. The association between cord blood adiponectin and neonatal adiposity was observed in neonates of obese mothers only.ConclusionsCord blood leptin and adiponectin concentrations were associated with ethnicity, maternal BMI and GDM, sex and gestational age. Both adipokines showed positive association with neonatal abdominal adiposity.
| S-EPMC8873009 | biostudies-literature
Project description:BACKGROUND:The human plasma proteome is important for many biological processes and targets for diagnostics and therapy. It is therefore of great interest to understand the interplay of genetic and environmental factors to determine the specific protein levels in individuals and to gain a deeper insight of the importance of genetic architecture related to the individual variability of plasma levels of proteins during adult life. METHODS:We have combined whole-genome sequencing, multiplex plasma protein profiling, and extensive clinical phenotyping in a longitudinal 2-year wellness study of 101 healthy individuals with repeated sampling. Analyses of genetic and non-genetic associations related to the variability of blood levels of proteins in these individuals were performed. RESULTS:The analyses showed that each individual has a unique protein profile, and we report on the intra-individual as well as inter-individual variation for 794 plasma proteins. A genome-wide association study (GWAS) using 7.3 million genetic variants identified by whole-genome sequencing revealed 144 independent variants across 107 proteins that showed strong association (P?<?6?×?10-11) between genetics and the inter-individual variability on protein levels. Many proteins not reported before were identified (67 out of 107) with individual plasma level affected by genetics. Our longitudinal analysis further demonstrates that these levels are stable during the 2-year study period. The variability of protein profiles as a consequence of environmental factors was also analyzed with focus on the effects of weight loss and infections. CONCLUSIONS:We show that the adult blood levels of many proteins are determined at birth by genetics, which is important for efforts aimed to understand the relationship between plasma proteome profiles and human biology and disease.
| S-EPMC7310558 | biostudies-literature
Project description:BackgroundUnderstanding the effect of blood donation and iron supplementation on iron balance will inform strategies to manage donor iron status.Study design and methodsA total of 215 donors were randomized to receive ferrous gluconate daily (37.5 mg iron) or no iron for 24 weeks after blood donation. Iron stores were assessed using ferritin and soluble transferrin receptor. Hemoglobin (Hb) iron was calculated from total body Hb. Total body iron (TBI) was estimated by summing iron stores and Hb iron.ResultsAt 24 weeks, TBI in donors taking iron increased by 281.0 mg (95% confidence interval [CI], 223.4-338.6 mg) compared to before donation, while TBI in donors not on iron decreased by 74.1 mg (95% CI, -112.3 to -35.9; p < 0.0001, iron vs. no iron). TBI increased rapidly after blood donation with iron supplementation, especially in iron-depleted donors. Supplementation increased TBI compared to controls during the first 8 weeks after donation: 367.8 mg (95% CI, 293.5-442.1) versus -24.1 mg (95% CI, -82.5 to 34.3) for donors with a baseline ferritin level of not more than 26 ng/mL and 167.8 mg (95% CI, 116.5-219.2) versus -68.1 mg (95% CI, -136.7 to 0.5) for donors with a baseline ferritin level of more than 26 ng/mL. A total of 88% of the benefit of iron supplementation occurred during the first 8 weeks after blood donation.ConclusionDonors on iron supplementation replaced donated iron while donors not on iron did not. Eight weeks of iron supplementation provided nearly all of the measured improvement in TBI. Daily iron supplementation after blood donation allows blood donors to recover the iron loss from blood donation and prevents sustained iron deficiency.
| S-EPMC4980154 | biostudies-literature
Project description:This is a study of 114 newborns aimed at identifying associations of cord blood methylation profiles with measures of newborn adiposity. Neonatal adiposity is a risk factor for childhood obesity. Investigating contributors to neonata adiposity is important for understanding early life obesity risk. Epigenetic changes of metabolic genes in cord blood may contribute to excessive neonatal adiposity and subsequent childhood obesity. This study aims to evaluate the association of cord blood DNA methylation patterns with markers of neonatal adiposity
2019-04-16 | GSE129841 | GEO
Project description:Adipose tissue (AT) plays a central role in the maintenance of whole-body energy homeostasis through release of adipokines. High-fat Western diet (HFWD)-consumption contributes to obesity, disruption of adipocyte metabolism, chronic systemic inflammation, and metabolic dysfunction (MetDys). MetDys is associated with impaired lung function, pulmonary hypertension, and asthma. Thirty-five percent of adults in the U.S. have MetDys, yet the impact of MetDys on susceptibility to occupational hazards is unknown. The aim of this study was to determine the potential of HFWD-consumption to alter inhaled crystalline silica dust-induced metabolic responses. Six-wk old male F344 rats were fed a HFWD (45 kcal % fat, sucrose 22.2 % by weight) or standard rat chow (STD, controls), and exposed to silica-inhalation (6 h/d, 5 d/wk, 39 d; Min-U-Sil 5®, 15 mg/m3) or filtered air. Indices of MetDys and systemic inflammation were measured at 0, 4, and 8 wk following cessation of silica exposure. At 8 wk post-exposure, silica reduced serum leptin and adiponectin levels, and increased arterial pulse frequency. HFWD-consumption induced weight gain, altered adipokines, liver, kidney, and pancreatic function, and increased tail artery blood flow. At 8 wk in HFWD + SIL-treated animals, the levels of serum pro-inflammatory cytokines (IFN-γ, CXCL-1, TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-10 and IL-13) were increased compared to STD + SIL but were less than HFWD + AIR-induced levels. In conclusion, consumption of a HFWD altered silica-induced metabolic responses and silica exposure disrupted AT endocrine function. These findings demonstrate previously unknown interactions between HFWD-consumption and occupational silica exposure.
| S-EPMC8683385 | biostudies-literature
Project description:Differentiating tuberculosis (TB) from pneumonia remains a challenge. We evaluated the cytokine profiles of whole blood cells from patients with TB (n = 38) or pneumonia (n = 30) and from healthy individuals (n = 30) before and after stimulating cells with ESAT-6 or lipopolysaccharide (LPS). When the percent change in the levels of gamma interferon (IFN-gamma) after stimulation with ESAT-6 was used in receiver operating characteristics (ROC) analysis (a graphic method to determine the diagnostic accuracy of a test) to identify a patient with TB, the area under the curve (AUC) was 90.4%, and a cutoff point of a 3.59% change produced a corresponding sensitivity, specificity, and accuracy of over 80%. When the change in IFN-gamma after stimulation of blood cells with LPS was used to identify a patient with pneumonia, the AUC reached 89.1%, and a cutoff point of 3.59% produced a sensitivity, specificity, and accuracy of approximately 80% each. When the change in interleukin-12 (IL-12) after stimulation of blood cells with LPS was selected to define a patient with pneumonia, the AUC was 85.2%, and a cutoff point of 2.08% gave a sensitivity, specificity, and accuracy of 80.0%, 78.9%, and 79.4%, respectively. We conclude that the percent change in IFN-gamma after stimulation of whole blood cells with ESAT-6 may differentiate patients with TB from patients with pneumonia. The percent change in IFN-gamma and IL-12 after LPS stimulation of whole blood cells could differentiate patients with pneumonia from patients with TB.
| S-EPMC2863376 | biostudies-literature
Project description:Although Parkinson's Disease (PD) is typically described in terms of motor symptoms, depression is a common feature. We explored whether depression influences blood-based genome-wide DNA methylation (DNAm) in 692 subjects from a population-based PD case-control study, using both a history of clinically diagnosed depression and current depressive symptoms measured by the geriatric depression scale (GDS). While PD patients in general had more immune activation and more accelerated epigenetic immune system aging than controls, the patients experiencing current depressive symptoms (GDS≥5) showed even higher levels of both markers than patients without current depressive symptoms (GDS<5). For PD patients with a history of clinical depression compared to those without, we found no differences in immune cell composition. However, a history of clinical depression among patients was associated with differentially methylated CpGs. Epigenome-wide association analysis (EWAS) revealed 35 CpGs associated at an FDR≤0.05 (569 CpGs at FDR≤0.10, 1718 CpGs at FDR≤0.15). Gene set enrichment analysis implicated immune system pathways, including immunoregulatory interactions between lymphoid and non-lymphoid cells (p-adj = 0.003) and cytokine-cytokine receptor interaction (p-adj = 0.004). Based on functional genomics, 25 (71%) of the FDR≤0.05 CpGs were associated with genetic variation at 45 different methylation quantitative trait loci (meQTL). Twenty-six of the meQTLs were also expression QTLs (eQTLs) associated with the abundance of 53 transcripts in blood and 22 transcripts in brain (substantia nigra, putamen basal ganglia, or frontal cortex). Notably, cg15199181 was strongly related to rs823114 (SNP-CpG p-value = 3.27E-310), a SNP identified in a PD meta-GWAS and related to differential expression of PM20D1, RAB29, SLC41A1, and NUCKS1. The entire set of genes detected through functional genomics was most strongly overrepresented for interferon-gamma-mediated signaling pathway (enrichment ratio = 18.8, FDR = 4.4e-03) and T cell receptor signaling pathway (enrichment ratio = 13.2, FDR = 4.4e-03). Overall, the current study provides evidence of immune system involvement in depression among Parkinson's patients.
| S-EPMC9618774 | biostudies-literature
Project description:BackgroundAnti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play important roles in the development of rheumatoid arthritis (RA). T cell immunoglobulin and mucin-domain containing-3 (TIM-3) is an immune-checkpoint molecule involved in inhibitory signaling. Galectin-9 (Gal-9) mediated ligation of TIM-3 induces the amelioration of autoimmune diseases. TIM-3 is expressed in synovial osteoclasts and involved in the rheumatoid bone destruction. The aim of this study was to investigate the relationships between inflammatory cytokines and immune-checkpoint molecules in RA patients.MethodsSerum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), soluble TIM-3 (sTIM-3) and Gal-9 were determined by ELISA. Patients were stratified into two groups based on ACPA titers: low-medium ACPA (ACPA <200 U/mL) and high ACPA (ACPA ≥200 U/mL). Serum levels of cytokines or immune-checkpoint molecules were evaluated between RA patients with low-medium ACPA titers and high ACPA titers.ResultsElevated serum levels of inflammatory cytokines were correlated with DAS28-ESR in RA patients. Although serum levels of sTIM-3 were elevated in RA patients, significant correlations between sTIM-3 and cytokines (IL-6 or TNF-α) were observed exclusively in RA patients with low-medium ACPA titers (<200 U/mL). Serum levels of IL-6 and TNF-α levels were significantly correlated with elevated Gal-9 levels regardless of ACPA status. A significant correlation between IL-6 and Gal-9 was observed in RA patients without advanced joint damage. Conversely, a significant correlation between TNF-α and Gal-9 was observed in RA patients with advanced joint damage.ConclusionsOur data indicated that there are positive correlations between circulating inflammatory cytokines and checkpoint molecules in RA patients and these interactions can be modulated by ACPA status or joint damage stage.
| S-EPMC8601500 | biostudies-literature
Project description:BackgroundBiological parameters are useful tools for understanding and monitoring complicated disease processes. In this study, we attempted to identify proteins associated with active pulmonary tuberculosis (TB) using a proteomic approach.MethodsTo assess TB-associated changes in the composition of human proteins, whole blood supernatants were collected from patients with active TB and healthy control subjects. Two-dimensional difference gel electrophoresis (2D-DIGE) was performed to analyze proteins with high molecular weights (approximately >20 kDa). Baseline protein levels were initially compared between patients with active TB and control subjects. Possible changes of protein patterns in active TB were also compared ex vivo between whole blood samples incubated with Mycobacterium tuberculosis (Mtb)-specific antigens (stimulated condition) and under unstimulated conditions. Immunoblot and enzyme-linked immunosorbent assays (ELISA) were performed to confirm differences in identified proteins.ResultsUnder the baseline condition, we found that the levels of retinol-binding protein 4 (RBP4), fetuin-A (also called ?-HS-glycoprotein), and vitamin D-binding protein differed between patients with active TB and control subjects on 2D gels. Immunoblotting results confirmed differential expression of RBP4 and fetuin-A. ELISA results further confirmed significantly lower levels of these two proteins in samples from patients with active TB than in control subjects (P < 0.0001). Mtb-specific antigen stimulation ex vivo altered clusterin expression in whole blood samples collected from patients with active TB.ConclusionsWe identified TB-associated proteins in whole blood supernatants. The dynamics of protein expression during disease progression may improve our understanding of the pathogenesis of TB.
| S-EPMC3072329 | biostudies-literature