Metabolomic Analysis of plasma samples from Non-Allergic Subjects and Profilin-Allergic Patients overexposed to Grass Pollen
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Blood
PROVIDER: ST000980 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:BackgroundAllergies are on the rise globally, with an enormous impact on affected individuals' quality of life as well as health care resources. They cause a wide range of symptoms, from slightly inconvenient to potentially fatal immune reactions. While allergies have been described and classified phenomenologically, there is an unmet need for easily accessible biomarkers to stratify the severity of clinical symptoms. Furthermore, biomarkers marking the success of specific immunotherapy are urgently needed.ObjectivesPlasma extracellular vesicles (pEV) play a role in coordinating the immune response and may be useful future biomarkers. A pilot study on differences in pEV content was carried out between patients with type I allergy, suffering from rhinoconjunctivitis with or without asthma, and voluntary non-allergic donors.MethodsWe examined pEV from 38 individuals (22 patients with allergies and 16 controls) for 38 chemokines, cytokines, and soluble factors using high-throughput data mining approaches.ResultsPatients with allergies had a distinct biomarker pattern, with 7 upregulated (TNF-alpha, IL-4, IL-5, IL-6, IL-17F, CCL2, and CCL17) and 3 downregulated immune mediators (IL-11, IL-27, and CCL20) in pEV compared to controls. This reduced set of 10 factors was able to discriminate controls and allergic patients better than the total array.ConclusionsThe content of pEV showed potential as a target for biomarker research in allergies. Plasma EV, which are readily measurable via blood test, may come to play an important role in allergy diagnosis. In this proof-of-principle study, it could be shown that pEV's discriminate patients with allergies from controls. Further studies investigating whether the content of pEVs may predict the severity of allergic symptoms or even the induction of tolerance to allergens are needed.
| S-EPMC8487953 | biostudies-literature
Project description:PurposeThe prevalence of "ocal allergic rhinitis" within individuals suffering from perennial rhinitis remains uncertain, and patients usually are diagnosed with non-allergic rhinitis. The aim of this study was to evaluate the prevalence of a potential "local allergic rhinitis" in subjects suffering from non-allergic rhinitis in a non-selected group of young students.Methods131 students (age 25.0 ± 5.1 years) with a possible allergic rhinitis and 25 non-allergic controls without rhinitis symptoms (age 22.0 ± 2.0 years) were recruited by public postings. 97 of 131 students with rhinitis were tested positive (≥3 mm) to prick testing with 17 frequent allergens at visit 1. Twenty-four 24 subjects with a house dust mite allergy, 21 subjects with a non-allergic rhinitis, and 18 non-allergic controls were further investigated at visit 2. Blood samples were taken, and nasal secretion was examined. In addition, all groups performed a nasal provocation test with house dust mite (HDM).ResultsIn serum and nasal secretion, total IgE and house dust mite specific IgE significantly differed between HDM positive subjects and controls. However, no differences between non-allergic subjects and control subjects were quantifiable. Neither a nasal provocation test nor a nasal IgE to HDM allergens showed a measurable positive response in any of the non-allergic rhinitis subjects as well as the healthy controls, whilst being positive in 13 subjects with HDM allergy.ConclusionsNasal IgE is present in subjects with HDM allergy, but not in non-allergic rhinitis. In the investigated non-selected population, exclusive local production of IgE is absent. By implication, therefore, our findings challenge the emerging concept of local allergic rhinitis.Study identifier at ClinicalTrials.gov: NCT02810535.
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Project description:Severe thrombocytopenia can be a determinant factor in the morbidity of Plasmodium vivax (Pv), the most widespread human malaria. Although immune mechanisms may drive Pv-induced severe thrombocytopenia (PvST), the current data on the cytokine landscape in PvST is scarce, and often conflicting. The analysis of the bidirectional circuit of inflammatory mediators and miRNAs would lead to a better understanding of the mechanisms underlying PvST.
2021-03-15 | GSE162304 | GEO
Project description:IntroductionMast cells are the primary effector cells of allergy. This study aimed at characterizing human peripheral blood-derived mast cells (PBdMC) from peanut allergic and non-allergic subjects by investigating whether the molecular and stimulus-response profile of PBdMC discriminate between peanut allergic and healthy individuals.MethodsPBdMC were generated from eight peanut allergic and 10 non-allergic subjects. The molecular profile (cell surface receptor expression) was assessed using flow cytometry. The stimulus-response profile (histamine release induced by secretagogues, secretion of cytokines/chemokines and changes in miRNA expression following anti-IgE activation) was carried out with histamine release test, luminex multiplex assay and miRNA arrays.ResultsExpression of activating receptors (FcϵRI, CD48, CD88, CD117, and C3aR) on PBdMC was not different among peanut allergic and non-allergic subjects. Likewise, inhibitory receptors (CD32, CD200R, CD300a, and siglec-8) displayed comparable levels of expression. Both groups of PBdMC were unresponsive to substance P, compound 48/80 and C5a but released comparable levels of histamine when stimulated with anti-IgE and C3a. Interestingly, among the secreted cytokines/chemokines (IL-8, IL-10, IL-13, IL-23, IL-31, IL-37, MCP-1, VEGF, GM-CSF) PBdMC from peanut allergic subjects showed a different secretion pattern of IL-31 compared to non-allergic subjects. Investigating miRNA expression from resting or activated PBdMC revealed no significantly difference between peanut allergic and non-allergic subjects.ConclusionThe molecular and stimulus-response profile revealed that PBdMC from peanut allergic subjects differently express IL-31 compared to non-allergic subjects. However, since only one altered parameter was found among 893 investigated, it is still questionable if the pathophysiological mechanisms of peanut allergy are revealed in PBdMC.
| S-EPMC6247235 | biostudies-literature
Project description:The assessment of kidney function within the first year following transplantation is crucial for predicting long-term graft survival. This study aimed to develop a robust and accurate model using metabolite profiles to predict early long-term outcomes in patient groups at the highest risk of early graft loss. A group of 61 kidney transplant recipients underwent thorough monitoring during a one-year follow-up period, which included a one-week hospital stay and follow-up assessments at three and six months. Based on their 12-month follow-up serum creatinine levels: Group 2 had levels exceeding 1.5 mg/dl, while Group 1 had levels below 1.5 mg/dl. Metabolites were detected by mass spectrometer and first pre-processed. Univariate and multivariate statistical analyses were employed to identify significant differences between the two groups. Nineteen metabolites were found to differ significantly in the 1st week, and seventeen metabolites in the 3rd month (adjusted p-value < 0.05, quality control (QC) < 30, a fold change (FC) > 1.1 or a FC < 0.91, Variable Influence on Projection (VIP) > 1). However, no significant differences were observed in the 6th month. These distinctive metabolites mainly belonged to lipid, fatty acid, and amino acid categories. Ten models were constructed using a backward conditional approach, with the best performance seen in model 5 for Group 2 at the 1st-week mark (AUC 0.900) and model 3 at the 3rd-month mark (AUC 0.924). In conclusion, the models developed in the early stages may offer potential benefits in the management of kidney transplant patients.
| S-EPMC10791079 | biostudies-literature
Project description:IntroductionVitiligo pathogenesis is complicated, and several possibilities were suggested. However, it is well-known that the metabolism of pigments plays a significant role in the pathogenicity of the disease.ObjectivesWe explored the role of amino acids in vitiligo using targeted metabolomics.MethodsThe amino acid profile was studied in plasma using liquid chromatography. First, 22 amino acids were derivatized and precisely determined. Next, the concentrations of the amino acids and the molar ratios were calculated in 31 patients and 34 healthy individuals.ResultsThe differential concentrations of amino acids were analyzed and eight amino acids, i.e., cysteine, arginine, lysine, ornithine, proline, glutamic acid, histidine, and glycine were observed differentially. The ratios of cysteine, glutamic acid, and proline increased significantly in Vitiligo patients, whereas arginine, lysine, ornithine, glycine, and histidine decreased significantly compared to healthy individuals. Considering the percentage of skin area, we also showed that glutamic acid significantly has a higher amount in patients with less than 25% involvement compared to others. Finally, cysteine and lysine are considered promising candidates for diagnosing and developing the disorder with high accuracy (0.96).ConclusionThe findings are consistent with the previously illustrated mechanism of Vitiligo, such as production deficiency in melanin and an increase in immune activity and oxidative stress. Furthermore, new evidence was provided by using amino acids profile toward the pathogenicity of the disorder.
| S-EPMC8464575 | biostudies-literature
Project description:IntroductionMultiple myeloma (MM), a malignant plasma cell disorder, is still an incurable disease. Thus, the identification of novel therapeutic targets is of utmost importance. Here, we evaluated the peripheral blood-based metabolic profile of patients with MM.Material & methodsPeripheral blood plasma levels of 188 endogenous metabolites, including amino acids, biogenic amines, acylcarnitines, glycerophospholipids, sphingomyelins, and hexoses were determined in patients with plasma cell dyscrasias: monoclonal gammopathy of undetermined significance, a precursor stage of MM (MGUS, n = 15), newly diagnosed MM, (NDMM, n = 32), relapsed/refractory MM (RRMM, n = 19) and in 25 healthy controls by mass spectrometry.ResultsPatients with NDMM, RRMM and MGUS have a substantially different metabolomic profile than healthy controls. The amount of eight plasma metabolites significantly differs between the NDMM and MGUS group: free carnitine, acetylcarnitine, glutamate, asymmetric dimethylarginine (ADMA) and four phosphatidylcholine (PC) species. In addition, the levels of octadecanoylcarnitine, ADMA and six PCs were significantly different between RRMM and MGUS patients. 13 different concentrations of metabolites were found between RRMM and NDMM patients (free carnitine, acetylcarnitine, creatinine, five LysoPCs and PCs). Pathway analyses revealed a distinct metabolic profile with significant alterations in amino acid, lipid, and energy metabolism in healthy volunteers compared to MGUS/MM patients.ConclusionWe identified different metabolic profiles in MGUS und MM patients in comparison to healthy controls. Thus, different metabolic processes, potentially the immunoregulation by indoleamine 2,3 dioxygenase-1 (IDO), which is involved in cancer development and progression supporting inflammatory processes in the tumor microenvironment and glutaminolysis, can serve as novel promising therapeutic targets in MM.
| S-EPMC6086450 | biostudies-literature
Project description:Nonclassic apparent mineralocorticoid excess (NC-AME) is proposed as a novel clinical condition with a mild phenotypic spectrum that ranges from normotension to severe hypertension. This condition is mainly characterized by a high serum cortisol to cortisone ratio (F/E) and concomitant low cortisone (E), however further metabolic changes in NC-AME have not been studied. A cross-sectional study was performed in a primary-care cohort of 396 Chilean subjects, which were classified in two groups: NC-AME (n = 28) and healthy controls (n = 27). A discovery study based in untargeted metabolomics assay in serum samples from both groups was performed by UPLC-Q-TOF/MS. Global metabolomic variations were assayed by principal component analysis and further compared by orthogonal partial least-squares discriminant analysis (OPLS-DA). NC-AME subjects exhibited higher values of blood pressure, fractional excretion of potassium, and lower plasma renin activity and urinary sodium to potassium ratio. Metabolomic analyses showed 36 differentially regulated metabolites between NC-AME and control subjects. A ROC curve analyses identified eight metabolites with high discriminatory capacity between NC-AME and control subjects. Moreover, gamma-L-glutamyl-L-methionine sulfoxide and 5-sulfoxymethylfurfural, exhibited significant association with cortisone, which are potential biomarkers of NC-AME, however further assays should elucidate its biological role in setup and progression of this phenotype.
| S-EPMC8387493 | biostudies-literature
Project description:BackgroundMajor depressive disorder (MDD) is a neuropsychiatric disorder caused by multiple factors. Although there are clear guidelines for the diagnosis of MDD, the direct and objective diagnostic methods remain inadequate thus far.MethodsThis study aims to discover peripheral biomarkers in patients with MDD and promote the diagnosis of MDD. Plasma samples of healthy controls (HCs, n = 52) and patients with MDD (n = 38) were collected, and then, metabolism analysis was performed using ultrahigh-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Heatmap analysis was performed to identify the different metabolites. Meanwhile, receiver operating characteristic (ROC) curves of these differential metabolites were generated.ResultsSix differential metabolites were found by LC-MS/MS analysis. Three of these were increased, including L-aspartic acid (Asp), diethanolamine, and alanine. Three were decreased, including O-acetyl-L-carnitine (LAC), cystine, and fumarate. In addition, LAC, Asp, fumarate, and alanine showed large areas under the curve (AUCs) by ROC analysis.ConclusionThe study explored differences in peripheral blood between depressed patients and HCs. These results indicated that differential metabolites with large AUCs may have the potential to be promising biomarkers for the diagnosis of MDD.
| S-EPMC8899025 | biostudies-literature
Project description:Overweight and obesity have high prevalence worldwide and assessing the metabolomic profile is a useful approach to study their related metabolic processes. In this study, we assessed the metabolomic profile of 1391 subjects affected by overweight and obesity, enrolled in the frame of the SPHERE study, using a validated LC-MS/MS targeted metabolomic approach determining a total of 188 endogenous metabolites. Multivariable censored linear regression Tobit models, correcting for age, sex, and smoking habits, showed that 83 metabolites were significantly influenced by body mass index (BMI). Among compounds with the highest association, aromatic and branched chain amino acids (in particular tyrosine, valine, isoleucine, and phenylalanine) increased with the increment of BMI, while some glycerophospholipids decreased, in particular some lysophosphatidylcholines (as lysoPC a C18:2) and several acylalkylphosphatidylcholines (as PC ae C36:2, PC ae C34:3, PC ae C34:2, and PC ae C40:6). The results of this investigation show that several endogenous metabolites are influenced by BMI, confirming the evidence with the strength of a large number of subjects, highlighting differences among subjects with different classes of obesity and showing unreported associations between BMI and different phosphatidylcholines.
| S-EPMC8064361 | biostudies-literature