scholarly journals Reduced serum levels of pro-inflammatory chemokines in Fragile X Syndrome

2020 ◽  
Author(s):  
Anke Van Dijck ◽  
Susana Barbosa ◽  
Patricia Bermudez-Martin ◽  
Olfa Khalfallah ◽  
Cyprien Gilet ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Robust Regression ◽  
Fragile X ◽  
Serum Levels ◽  
Unsupervised Clustering ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Clustering Method ◽  
Inflammatory Chemokines ◽  
Healthy Control

Abstract Background: Fragile X syndrome (FXS) is the most frequent cause of inherited intellectual disability and the most commonly identified monogenic cause of autism. Recent studies have shown that long-term pathological consequences of FXS are not solely confined to the central nervous system (CNS) but rather extend to other physiological dysfunctions in peripheral organs. To gain insights into possible immune dysfunctions in FXS, we profiled a large panel of immune-related biomarkers in the serum of FXS patients and healthy controls. Methods: We have used a sensitive and robust Electro Chemi Luminescence (ECL)-based immunoassay to measure the levels of 52 cytokines in the serum of n=25 FXS patients and n=29 healthy controls. We then used univariate statistics and multivariate analysis, as well as an advanced unsupervised clustering method, to identify combinations of immune-related biomarkers that could discriminate FXS patients from healthy individuals. Results: While the majority of the tested cytokines were present at similar levels in FXS patients and healthy individuals, nine chemokines, CCL2, CCL3, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26 and CXCL10, were present at much lower levels in FXS patients. Using robust regression, we show that six of these biomarkers (CCL2, CCL3, CCL11, CCL22, CCL26 and CXCL10) were negatively associated with FXS diagnosis. Finally, applying the K-sparse unsupervised clustering method to the biomarker dataset allowed for the identification of two subsets of individuals, which essentially matched the FXS and healthy control categories. Conclusions: Our data show that FXS patients exhibit reduced serum levels of several chemokines. This paves the way for further study of immune phenotypes in FXS patients.

scholarly journals Reduced serum levels of pro-inflammatory chemokines in Fragile X Syndrome

2019 ◽  
Author(s):  
Anke Van Dijck ◽  
Susana Barbosa ◽  
Patricia Bermudez-Martin ◽  
Olfa Khalfallah ◽  
Cyprien Gilet ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Robust Regression ◽  
Fragile X ◽  
Serum Levels ◽  
Unsupervised Clustering ◽  
Healthy Controls ◽  
Clustering Methods ◽  
Healthy Individuals ◽  
Clustering Method ◽  
Diagnosis And Prognosis

Abstract Background: Fragile X syndrome (FXS) is the most frequent cause of inherited intellectual disability and the most commonly identified monogenic cause of autism. Recent studies have shown that long-term pathological consequences of FXS are not solely confined to the central nervous system (CNS) but rather extend to other physiological dysfunctions in peripheral organs. To gain insights into possible immune dysfunctions in FXS, we profiled a large panel of immune-related biomarkers in the serum of FXS patients and healthy controls. Methods: We have used a sensitive and robust Electro Chemi Luminescence (ECL)-based immunoassay to measure the levels of 52 cytokines in the serum of n=25 FXS patients and n=29 healthy controls. We then used univariate statistics and multivariate analysis, as well as an advanced unsupervised clustering method, to identify combinations of immune-related biomarkers that could discriminate FXS patients from healthy individuals. Results: While the majority of the tested cytokines were present at similar levels in FXS patients and healthy individuals, nine chemokines, CCL2, CCL3, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26 and CXCL10, were present at much lower levels in FXS patients. Using robust regression, we show that six of these biomarkers (CCL2, CCL3, CCL11, CCL22, CCL26 and CXCL10) were negatively associated with FXS diagnosis. Finally, applying the K-sparse unsupervised clustering method to the biomarker dataset allowed for the identification of two subsets of individuals, which essentially matched the FXS and healthy control categories. Conclusions: Our data show that FXS patients exhibit reduced serum levels of several chemokines and may therefore exhibit impaired immune responses. The present study also highlights the power of unsupervised clustering methods to identify combinations of biomarkers for diagnosis and prognosis in medicine.

scholarly journals Reduced serum levels of pro-inflammatory chemokines in Fragile X Syndrome

2019 ◽  
Author(s):  
Anke Van Dijck ◽  
Susana Barbosa ◽  
Patricia Bermudez-Martin ◽  
Olfa Khalfallah ◽  
Cyprien Gilet ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Fragile X ◽  
Serum Levels ◽  
Unsupervised Clustering ◽  
Healthy Controls ◽  
Clustering Methods ◽  
Healthy Individuals ◽  
Clustering Method ◽  
Diagnosis And Prognosis ◽  
Inflammatory Chemokines

Abstract Background: Fragile X syndrome (FXS) is the most frequent cause of inherited intellectual disability and the most commonly identified monogenic cause of autism. Recent studies have shown that long-term pathological consequences of FXS are not solely confined to the central nervous system (CNS) but rather extend to other physiological dysfunctions in peripheral organs. To gain insights into possible immune dysfunctions in FXS, we profiled a large panel of immune-related biomarkers in the serum of FXS patients and healthy controls. Methods: We have used a sensitive and robust ElectroChemiLuminescence (ECL)-based immunoassay to measure the levels of 52 cytokines in the serum of n=25 FXS patients and n=29 healthy controls. We then used univariate statistics and multivariate analysis, as well as an advanced unsupervised clustering method, to identify combinations of immune-related biomarkers that could discriminate FXS patients from healthy individuals. Results: While the majority of the tested cytokines were present at similar levels in FXS patients and healthy individuals, nine chemokines, CCL2, CCL3, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26 and CXCL10, were present at much lower levels in FXS patients. Applying the K-sparse unsupervised clustering method to the biomarker dataset allowed for the identification of two subsets of individuals, which essentially matched the FXS and healthy control categories. Conclusions: Our data suggest that FXS patients exhibit reduced serum levels of several chemokines and may therefore exhibit impaired immune responses. The present study also highlights the power of unsupervised clustering methods to identify combinations of biomarkers for diagnosis and prognosis in medicine.

scholarly journals Reduced serum levels of pro-inflammatory chemokines in fragile X syndrome

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Anke Van Dijck ◽  
Susana Barbosa ◽  
Patricia Bermudez-Martin ◽  
Olfa Khalfallah ◽  
Cyprien Gilet ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Fragile X ◽  
Serum Levels ◽  
Inflammatory Chemokines

scholarly journals Antibodies to Der p 1 and Der p 2 in allergic patients

2021 ◽  
Vol 49 (2) ◽  
pp. 46-52
Author(s):  
Renata Harumi Cruz ◽  
Leandro Hideki Ynoue ◽  
Carolina Sanchez Aranda ◽  
Dirceu Solé ◽  
Antonio Condino Neto
Keyword(s):  
Serum Levels ◽  
Specific Ige ◽  
Protective Mechanism ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Th2 Response ◽  
Iga Antibodies ◽  
Der P 1 ◽  
Der P 2

Introduction and objectives: Atopic individuals are characterized by increased IgE production and Th2 response if exposed to certain antigens. It is known that the mother transfers antimite antibodies to the fetus and newborn, IgG thru the placenta, and IgA thru breastfeeding, but it is not clear whether there is a protective mechanism mediated by them concerning the development of future allergies. This study aimed to compare the levels of IgA, IgG, and IgE antibodies specific to Der p 1 and Der p 2 between atopic and healthy individuals.Methods: Serum samples of 98 patients and 44 healthy controls were subjected to quantification for specific IgE, IgG, and IgA antibodies against Der p 1 and Der p 2 by ImmunoCap® and ELISA, and subjected to statistical analysis as indicated.Results: Atopic patients had higher serum levels of IgE, IgG, and IgA specific to Der p 1 and Der p 2. The correlation was more robust between IgE and IgG antibodies.Conclusions: Allergic patients produce higher levels of antibodies against Der p 1 and Der p 2 compared with healthy individuals. The mechanisms involved still require detailed studies.

scholarly journals Shortened platelet half-life in multiple myeloma

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 514-520
Author(s):  
E Fritz ◽  
H Ludwig ◽  
W Scheithauer ◽  
H Sinzinger
Keyword(s):  
Multiple Myeloma ◽  
Half Life ◽  
Serum Levels ◽  
Statistical Correlation ◽  
Control Group ◽  
Healthy Controls ◽  
Platelet Factor ◽  
Healthy Control

Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half- life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained-- intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.

scholarly journals Genotoxicity in Patients on Long-term Proton Pump Inhibitor Therapy in Korea: A Nested Case-control, Prospective, Pilot Study

2020 ◽  
Vol 20 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Youn I Choi ◽  
Jun-Won Chung ◽  
Dong Kyun Park ◽  
Kyoung Oh Kim ◽  
Kwang An Kwon ◽  
...  
Keyword(s):  
Pilot Study ◽  
Medical History ◽  
Proton Pump ◽  
Serum Levels ◽  
Self Report ◽  
Healthy Controls ◽  
Control Subjects ◽  
Increased Risk ◽  
Healthy Control

Background/Aims: Although proton pump inhibitors (PPIs) remain a mainstay for the suppression of gastric acid secretion, long-term PPI use is associated with side effects. However, the genotoxicity associated with long-term PPI use is unclear.Materials and Methods: This prospective observational pilot study enrolled patients who had been on PPIs for >1 year and healthy controls from July 2015 to August 2016. The subjects completed self-report questionnaires pertaining to their drug and medical history, and only those with no medical history and a ≥2-year wash-out period (for drugs other than PPIs) were included. We collected peripheral-blood lymphocytes from long-term PPI users and healthy controls and analyzed the genotoxicity by using the cytokinesis-block micronucleus cytome assay; we also determined the fasting serum levels of pyridoxine, folate, cobalamin, and homocysteine.Results: Ten long-term PPI users and 40 healthy control subjects were enrolled. The median serum pyridoxine, folate, cobalamin, and homocysteine levels were not significantly different between the groups. The median frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (Nbuds) per 1,000 binucleated cells, in long-term PPI users and healthy controls, were 30.3 and 16.3 (<i>P</i><0.005), 2.5 and 1.8 (<i>P</i><0.005), and 9.3 and 5.0 (<i>P</i><0.005), respectively. Even after adjustment for confounding factors, the OR of the MNi, NPBs, and Nbuds for long-term PPI users compared with healthy control subjects were 14.1 (<i>P</i><0.001), 2.0 (<i>P</i>=0.001), and 1.3 (<i>P</i>=0.3), respectively.Conclusions: Long-term PPI use was significantly associated with an increased risk of genotoxicity after adjustment for age, sex, body mass index, medical history, drug history, and the serum levels of vitamins.

scholarly journals Value of immune factors for monitoring risk of lung cancer in patients with interstitial lung disease

2019 ◽  
Vol 47 (7) ◽  
pp. 3344-3353
Author(s):  
Ning Li ◽  
Haisheng Hu ◽  
Ge Wu ◽  
Baoqing Sun
Keyword(s):  
Lung Cancer ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Serum Levels ◽  
Scaling Analysis ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Reactive Protein ◽  
Increased Risk ◽  
Immune Factors

Objective Patients with interstitial lung disease (ILD) are at increased risk of developing lung cancer. We aimed to investigate the clinical significance of serum immune factors in this progression. Methods We retrospectively screened a hospital database from January 2012 to December 2016 for patients with lung cancer and ILD. We measured serum levels of C3, C4, IgA, IgG, IgM, C-reactive protein (CRP), ceruloplasmin (CER), and rheumatoid factor in these patients and in healthy controls. Results We analyzed data for 262 patients with lung cancer, 220 with ILD, and 57 healthy controls. CER levels were significantly higher in patients with lung cancer (0.35 ± 0.10 g/L) compared with both ILD patients (0.31 ± 0.25 g/L) and healthy individuals (0.25 ± 0.04 g/L). C3 and C4 levels were both significantly higher in healthy individuals compared with patients with lung cancer (C3: 1.70 ± 0.29 vs 1.04 ± 0.26 g/L, C4: 0.27 ± 0.24 vs 0.24 ± 0.09 g/L) and ILD (C3: 1.70 ± 0.29 vs 0.97 ± 0.25 g/L, C4: 0.27 ± 0.24 vs 0.21 ± 0.09 g/L). Optimal scaling analysis demonstrated that lung cancer was closely associated with CRP, CER, C3, and C4. Conclusions Increased levels of CRP and CER and decreased levels of C3 and C4 may identify patients with ILD at high risk of developing lung cancer.

scholarly journals Urine-Derived Epithelial Cell Lines: A New Tool to Model Fragile X Syndrome (FXS)

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2240
Author(s):  
Marwa Zafarullah ◽  
Mittal Jasoliya ◽  
Flora Tassone
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Fragile X Syndrome ◽  
Cell Lines ◽  
Behavioral Problems ◽  
Cell Model ◽  
Fragile X ◽  
Healthy Controls ◽  
Full Mutation ◽  
Epithelial Cell Lines

Fragile X syndrome (FXS) is an X-linked neurodevelopmental condition associated with intellectual disability and behavioral problems due to the lack of the Fragile X mental retardation protein (FMRP), which plays a crucial role in synaptic plasticity and memory. A desirable in vitro cell model to study FXS would be one that can be generated by simple isolation and culture method from a collection of a non-invasive donor specimen. Currently, the various donor-specific cells can be isolated mainly from peripheral blood and skin biopsy. However, they are somewhat invasive methods for establishing cell lines from the primary subject material. In this study, we characterized a cost-effective and straightforward method to derive epithelial cell lines from urine samples collected from participants with FXS and healthy controls (TD). The urine-derived cells expressed epithelial cell surface markers via fluorescence-activated cell sorting (FACS). We observed inter, and the intra-tissue CGG mosaicism in the PBMCs and the urine-derived cells from participants with FXS potentially related to the observed variations in the phenotypic and clinical presentation FXS. We characterized these urine-derived epithelial cells for FMR1 mRNA and FMRP expression and observed some expression in the lines derived from full mutation mosaic participants. Further, FMRP expression was localized in the cytoplasm of the urine-derived epithelial cells of healthy controls. Deficient FMRP expression was also observed in mosaic males, while, as expected, no expression was observed in cells derived from participants with a hypermethylated full mutation.

scholarly journals Distinct effects of over-general autobiographical memory on suicidal ideation among depressed and healthy people

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wen Jiang ◽  
Guangtao Hu ◽  
Jingxuan Zhang ◽  
Ken Chen ◽  
Dongni Fan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Suicidal Ideation ◽  
Autobiographical Memory ◽  
Childhood Trauma ◽  
Study Data ◽  
Path Model ◽  
Control Group ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Healthy Control

Abstract Background Childhood trauma and over-general autobiographical memory (OGM) are crucial risk factors of suicide. This study aimed to investigate whether suicidal ideation was predicted by one’s childhood trauma and OGM and the mechanism of OGM underlying suicidal ideation in depression patients and healthy controls. Methods A total of 180 depression patients and 176 matched healthy individuals were recruited in this study. Data were analyzed using descriptive statistics, and Pearson’s correlation coefficient was obtained. Path analysis was conducted to test a meditational model. The multigroup comparison was applied to find differences between groups. Results Significant differences were detected between depression patients and healthy controls with respect to childhood trauma, OGM, suicidal ideation, and suicidal behavior. OGM was positively correlated with both current and worst-point suicidal ideation in the depression group and significantly correlated with worst-point suicidal ideation in the healthy control group. The path model showed that childhood trauma had a direct impact on the current suicidal ideation directly, and an indirect influence through OGM and worst-point suicidal ideation. Multigroup analysis further demonstrated that OGM affected and mediated the current suicidal ideation due to childhood trauma in depression patients, whereas only worst-point suicidal ideation was affected in healthy controls. Conclusions The OGM mediates suicidal ideation in depression patients, but only affects the worst-point suicidal ideation in the healthy controls. As it is one of the major risk factors of suicidal ideation in depression, amelioration of OGM might be an useful method to reduce or prevent suicidal ideation in depression patients.

scholarly journals Extracellular Vesicle-Based Detection of Pancreatic Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yesim Verel-Yilmaz ◽  
Juan Pablo Fernández ◽  
Agnes Schäfer ◽  
Sheila Nevermann ◽  
Lena Cook ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Roc Curves ◽  
Serum Levels ◽  
Extracellular Vesicle ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Healthy Controls ◽  
Precursor Lesions ◽  
Healthy Individuals ◽  
Serum Samples

Due to a grim prognosis, there is an urgent need to detect pancreatic ductal adenocarcinoma (PDAC) prior to metastasis. However, reliable diagnostic imaging methods or biomarkers for PDAC or its precursor lesions are still scarce. ADAM8, a metalloprotease-disintegrin, is highly expressed in PDAC tissue and negatively correlates with patient survival. The aim of our study was to determine the ability of ADAM8-positive extracellular vesicles (EVs) and cargo microRNAs (miRNAs) to discriminate precursor lesions or PDAC from healthy controls. In order to investigate enrichment of ADAM8 on EVs, these were isolated from serum of patients with PDAC (n = 52), precursor lesions (n = 7) and healthy individuals (n = 20). Nanoparticle Tracking Analysis and electron microscopy indicated successful preparation of EVs that were analyzed for ADAM8 by FACS. Additionally, EV cargo analyses of miRNAs from the same serum samples revealed the presence of miR-720 and miR-451 by qPCR and was validated in 20 additional PDAC samples. Statistical analyses included Wilcoxon rank test and ROC curves. FACS analysis detected significant enrichment of ADAM8 in EVs from patients with PDAC or precursor lesions compared to healthy individuals (p = 0.0005). ADAM8-dependent co-variates, miR-451 and miR-720 were also diagnostic, as patients with PDAC had significantly higher serum levels of miR-451 and lower serum levels of miR-720 than healthy controls and reached high sensitivity and specificity (AUC = 0.93 and 1.00, respectively) to discriminate PDAC from healthy control. Thus, detection of ADAM8-positive EVs and related cargo miR-720 and miR-451 may constitute a specific biomarker set for screening individuals at risk for PDAC.

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