scholarly journals INF-γ Plasma Level and Polymorphism Significance in Autastic Spectrum Disorder, A Controlled Study in Basrah

2020 ◽  
pp. 1-5
Author(s):  
Khulood Abdulrazaq Kaleel ◽  
◽  
Wijdan Nazar Ibraheim ◽  
Qussay Nfawa Thaqab Almaliki ◽  
◽  
...  

ASD are particularly heterogeneous developmental conditions. Many arguments clarified a central function for dysregulation of immune system in ASD and many ASD hazard genes encode the immune system elements along with other risk factors. There is also evidence of continuing dysregulation of immune system in people with ASD and in animal models of this condition. Objectives: This study was performed to investigate the relationship between the IFN-γ + 874 gene polymorphism and INF - γ plasma level with susceptibility to ASD Methods: Polymorphism detection analysis was performed on 194 subjects from Basra south Iraq. 94 patients with ASD, (78 (83%) males and 16 (17%) females), their age ranging from 2 to 13 years, and 100 children apparently healthy control group matching for the same age and sex The IFN-γ gene polymorphism (+874A/T) was genotyped through a specific sequence primer polymerase chain reaction (SSP-PCR). For all participant the plasma level of INF-γ was determined by ELISA KIT (Elabscience, USA, Catalog No: E-EL-H0108), followed the manufacturer instructions Results: showed sufficient differences in the plasma concentration of INF between children with autism and the none group: 24.87 pg/mm2 18.86 pg/ mm respectively, with significant increase in plasma concentration of IFN of male and female of autistic group as compare to control group. Results of iterative distribution of INF-γ+874 gene polymorphism showed heterogeneous results between autistic group and control group, as the T allele was scored in autistic group 23.4% in compared with A allele which scored 79.7%, while in control group the T allele was scored 67% in compared with A allele which was scored 85%. AA genotypes of IFN-γ+874 showed higher recurrence among autistic group in compared to control group,(76.5% vs 33% respectively), while TA genotypes of IFN-γ+874 showed lower recurrence in autistic group when compared to control group,(3.2% vs 52% respectively),and IFN-γ+874 TT genotypes scored 20.2% in autistic patients and 15% was scored in control group ASD susceptibility is associated with the T allele of +874 rs2430561 with increase plasma level of IFN-γ which may have role in the severity of behavioural changes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3847-3847 ◽  
Author(s):  
Yunfeng Cheng ◽  
Shanhua Zou ◽  
Feng Li

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against self-antigens and T-cell mediated cytotoxicity. Toll-like receptors (TLRs) are pattern recognition receptors important in mediating the immune response and their activation can lead to production of cytokines. Recent data suggest that TLR2 and TLR4 are crucial for the production of inflammatory cytokines and play central role in autoimmune diseases, yet little is known about their roles in ITP. Here we examined the gene expressions of TLR2 and TLR4 in ITP patients. We hypothesize that significant differences will exist between pre-treatment and post-treatment in ITP patients with similar changes reflected in the plasma concentration of cytokines. Total RNA was extracted from mononuclear cells obtained from 12 ITP patients and 15 healthy subjects. TLR2 and TLR4 mRNA expression levels were analyzed using a quantitative real-time PCR method and their protein expressions were validated by western blot. Plasma concentrations of cytokines IL-2, IFN-γ and TNF-α were measured by ELISA. Correlation analyses were carried out between the mRNA expression levels of TLR2 or TLR4 and the plasma levels of IL-2, IFN-γ and TNF-α. The gene expression of TLR2 and TLR4 were significantly increased in ITP patients comparing to healthy control group (p < 0.05 and p < 0.01, respectively). In addition their mRNA expression levels were decreased back into normal range after remission in 8 patients (p > 0.05, compared to healthy control group). Significantly positive correlations were found between the TLR2 mRNA expression level and the plasma concentration of IFN-γ or TNF-α (R = 0.75, p < 0.05; R = 0.83, p < 0.05, respectively). Changes in the gene expression of TLR4 and in the plasma concentration of IFN-γ or TNF-α were also significantly correlated (R = 0.82, p < 0.05; R = 0.88, p < 0.05, respectively). Directional changes in TLR2 / TLR4 and IFN-γ /TNF-α expression were concordant. However, there was no correlation found between TLR2 / TLR4 and IL-2. Differences in TLR2 and TLR4 expression strongly correlated with changes in IFN-γ and TNF-α suggest that the increased gene expressions of TLR2 and TLR4 in ITP patients may contribute to the pathophysiological progression of this disease by increasing the secretion of IFN-γ and TNF-α. Additional studies need to be performed to further clarify the role of TLRs -cytokines pathway in ITP.


Open Medicine ◽  
2010 ◽  
Vol 5 (1) ◽  
pp. 36-40 ◽  
Author(s):  
Chris Pruunsild ◽  
Kaire Heilman ◽  
Kersti Zilmer ◽  
Karin Uibo ◽  
Hille Liivamägi ◽  
...  

AbstractTo examine the plasma levels of MPO in oligoarthritis and polyarthritis subtypes of JIA in comparison with healthy age-matched controls. Thirty-eight JIA patients (25 girls and 13 boys) aged 9.1–11.8 years and 23 healthy controls (8 girls and 15 boys) participated in the study. Twenty-one patients had oligoarthritis (8 with extended oligoarthritis) and 17 had polyarthritis (among them three were seropositive). The plasma concentration of MPO was measured by the ELISA technique (OxisResearchTM, BIOXYTECH® MPO-EIATM, Portland, OR USA). The mean plasma concentration of MPO in the JIA group was significantly higher than in the control group (76.6±24.8 µg/L versus 62.7±15.6 µg/L; p=0.01). Patients with polyarthritis presented a significantly higher mean plasma MPO level than patients with oligoarthritis (81.3±25.6 µg/L and 62.1±27.1 µg/L, respectively; p=0.02). Different subtypes of JIA may have different MPO-related backgrounds. MPO is a new potent inflammatory marker. Patients with polyarthritis have higher mean plasma MPO levels than patients with oligoarthritis and may therefore have an enhanced risk for subclinical oxidative stress-related atherogenic promotion.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1236-1236
Author(s):  
Marco Aurelio Salvino ◽  
Marilda Souza Goncalves ◽  
Bruno A. V. Cerqueira ◽  
Larissa A Medeiros ◽  
Flavio Lins ◽  
...  

Abstract Introduction Idiopathic acquired aplastic anemia (AAA) is a rare and life-threatening disease, characterized by pancytopenia. Its immune-mediated physiopathology is not yet fully understood. However, important associations have been reported in AAA, which include the association with certain HLAs, the presence of a PNH clone in 40-50% of cases, occurrence of a hepatitis associated variant in about 5-10% of cases, the occurrence of interferon gamma (IFN-g) and tumor necrosis factor alpha (TNF-a) producing T cells in the peripheral blood and bone marrow cells. Not much is known about cytokine gene polymorphisms in AAA and its relationship with HLA alleles. The IFN-γ +874 A/T gene polymorphism, and specially the +874TT genotype, have been associated with elevated levels of IFN-γ production. The individuals can present 3 different phenotype (TT, TA or AA). Some groups have demonstrated that the TT (the IFN-gamma “hyper-producer type”) is possibly overrepresented in AA patients and correlates with susceptibility to the disease. In order to better understand the relationship between these immune parameters, we investigated the associations between IFN-g gene polymorphism in AAA patients and its relationship with the presence of HLADR15 (identified as of greater importance in our local patients). Materials and methods In this study we analyze the variations of the gene polymorphism at position +874 interferon in 30 consecutive patients with confirmed diagnosis of AAA,in 2012 and 2013, at the Federal University of the State of Bahia Hospital/Brazil. Diagnosis of AAA was confirmed by bone marrow biopsy. Patients also had their HLA typing and were tested for the IFN-gamma gene polymorphism at +874 T/A position using the ARMS methodology described by Pravica. As controls, 116 healthy individuals from the same population (Bahia/Brazil) were tested for these polymorphism. The analysis of the association between the gene polymorphism and the chances of developing AAA, and the polymorphism and the HLA-DR15, were performed using qui-square/exact fisher test. The results were expressed as OR. Results We have found genotypic frequency of the A allele in 65%(n=39/60) in the aplastic patients (control 64.2%, n = 232, OR 1.05, p=0.87). The T allele was found in 35%(n =21/60)of the cases (control 34.6%, OR 0.95, p=0.87). Thus, there was no difference between the genotypic frequency of the alleles among patients with aplasia and the control group. In addition, there was NO difference between the frequency of the phenotype (TT, AT or AA) between patients with AAA and control group, respectively 16,5%, 36,5%, 46% (AAA, n =30) versus 18.1% , 35.3%, 46.6% (n = 116 control) (p=n.s.). The association of the polymorphism was tested and compared to the HLA-DR15. There was NO association between the IFN-gamma gene polymorphisms and the presence of HLADR15 (p =,90). Conclusion In our brazilian cohort, the +874 T/A IFN-gamma gene polymorphism was Not associated with the onset of AAA. Also, there was No association between IFN-gamma gene polymorphism and the antigen HLA-DR15. TT phenotype, possibly the predisposing one for disease, was expressed only in 15% of patients with AAA. These findings corroborate the presence of a much more complex pathogenesis in AAA ,and that, regional differences in genetic and immune mechanisms may co-exist. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 8 (A) ◽  
pp. 70-75
Author(s):  
Roslinda Damanik ◽  
Elmeida Effendy ◽  
M. Surya Husada

BACKGROUND: Massive heritability occurs in schizophrenia. Gene identification which is defenceless against this disorder is difficult to be proven. The potential aspect of gen vulnerability in developing schizophrenic symptoms, for instance, is shown by several complex gene of tumor necrosis factor-alpha, interleukin (IL)-1, IL-6, and IL-10. AIMS: The aim of the study was to investigate the relationship of gene polymorphism of interferon-gamma (IFN-γ) +874 A/T and schizophrenia symptoms to Batak’s schizophrenic patients. METHODS: This study is a case–control study involved with 248 subjects from Prof. M. Ildrem Medan Hospital. The subjects were divided into two groups, the first group (124 subjects) was recruited as the case group, while the other 124 subjects were grouped as control cases with ages of 20–55 years of old. The case study group was hospitalized patients in the hospital, while the control group is those donors in the blood transfusion unit at Pirngadi General Hospital, Medan, Indonesia. IFN-γ +874 A/T gene polymorphism was examined by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Genotype AT frequencies from gen IFN-γ +874 A/T were found higher in case study than those from control groups, which were accounted for 43.5% and 41.1%, respectively, with p = 0.005, odds ratio (OR) = 2.83 95% confidence interval (CI) 1.36–5.86. The allele T was displayed higher in case group compared to control groups contributed for 46.0% and 33.5%, respectively, with p = 0.006, OR = 0.59 95% (CI) 0.41–0.85, (p = 0.006). CONCLUSIONS: There was a relationship between gen IFN-γ +874 A/T and schizophrenia on Batak ethnicity with schizophrenic disorder. The genotype AT contributes for increasing schizoprenic risk up to 2.83 times.


Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Arezou Sayad ◽  
Abolfazl Movafagh

Multiple sclerosis (MS) is a chronic neuroinflammatory demyelinating disease of the central nervous system. The cytokine genes are involved in autoimmune diseases such as MS. In this study, we report the influence of −330 interleukin-2 (IL2) gene polymorphism on its plasma levels in a group of Iranian MS patients. In this study 100 MS patients and 100 ethnically, age, and sex matched healthy controls were selected from Medical Genetics Department of Sarem Women Hospital. Blood samples of all individuals were collected in EDTA tubes. The restriction fragment length polymorphism PCR (RFLP) method was applied to determine various alleles and genotypes in these individuals. Plasma concentration of IL2 was measured in all the samples using human IL2 kit. The frequency of −330 T/T IL2 genotype was higher in MS patients compared to normal individuals. Accordingly, the plasma levels of IL2 were significantly higher (P<0.0001) in patients when compared to the control group. In conclusion, in case of MS patients the −330 T/T IL2 genotype is associated with higher plasma levels of IL2.


Author(s):  
D.C. Dominguez ◽  
J.T. Ellzey

Peroxisomes which participate in 1ipid metabolism have been shown to be altered in several metabolic disorders and toxic conditions. In alcoholic liver disease, the single lesion most frequently found is lipid accumu1ation in hepatocytes. However, the mechanisms for this 1ipid accumu1ation are not clear. The occurrence of modifications of liver peroxisomes due to excess alcohol consumption has not been subjected to a controlled study. We utilized a combination of cytochemica1 and morphometrictechniques to study the size and number of liver peroxisomes in rats fed an alcohol-supplemented diet compared to those of matched-paired control animals.Male Sprague-Daw1ey rats (400-500 g) received a liquid diet. The experimental group (N = 5/group) was fed a diet containing 30% ethanol-derived calories (EDC) and the control group was fed an isocaloric diet to 30% EDC. A pair feeding procedure was employed to control for caloric intake. Small pieces of liver randomly selected, were fixed in 2.3% -glutaraldehyde in 0.1 M sodium cacodylate buffer, pH 7.2, incubated in a DAB medium and postfixed with. 2% aqueous osmium tetroxide. EM photographs were taken from sections of 3 tissue blocks from each sample (7,200X) with a Zeiss EM10-A (60 kV). With the use of a point counting method and a digital planimeter the volume density (Vv) and numerical density (Nv) were determined.


1991 ◽  
Vol 66 (04) ◽  
pp. 426-429 ◽  
Author(s):  
Marcel Levi ◽  
Anthonie W A Lensing ◽  
Harry R Büller ◽  
Paolo Prandoni ◽  
Gerard Dooijewaard ◽  
...  

SummaryIn the present study 57 consecutive patients with a first episode of venographically proven deep vein thrombosis were investigated to evaluate the release of tissue-type plasminogen activator (t-PA) and of urokinase-type plasminogen activator (u-PA) in response to DDAVP stimulation as well as the resting plasminogen activator inhibitor (PAI) concentration, comparing this to the results obtained in 66 similar patients with a clinical suspicion of thrombosis but with a normal venogram. All assays were performed without knowledge of the patient's status.Four patients in the deep vein thrombosis-group (7%) had an absent u-PA antigen response upon DDAVP infusion, while a normal response was observed in all control subjects. Patients and controls showed similar increases in t-PA antigen level upon DDAVP. High resting PAI antigen levels were encountered in 5 patients in the deep vein thrombosis-group (9%) and in 6 subjects in the control group (9%).The results from this controlled study indicate that a defective release of u-PA may occur in patients with deep vein thrombosis and may have pathogenetic significance. Furthermore it is concluded that elevation of PAI levels cannot be considered as a specific risk factor for venous thrombosis.


1997 ◽  
Vol 77 (02) ◽  
pp. 248-251 ◽  
Author(s):  
Lena Norlund ◽  
Johan Holm ◽  
Bengt Zöller ◽  
Ann-Kristin Öhlin

SummaryEndothelial dysfunction and haemostatic imbalance are believed to be important aetiological factors in the development of acute coronary syndromes. Thrombomodulin (TM) is an integral membrane protein crucial for normal endothelial function and activation of the protein C anticoagulant pathway. We have investigated the importance of a common C/T dimorphism in the TM gene (nucleotide 1418) for development of premature myocardial infarction (MI). The C/T dimorphism predicts an Ala455 to Val replacement in the sixth EGF-like domain of TM. The dimorphism was investigated in 97 MI survivors and 159 healthy controls. The C allele was significantly more frequent among patients than controls (p = 0.035). The allele frequency for the C allele was 0.82 in the patients and 0.72 in the control group. The plasma concentration of TM was investigated among healthy controls but was not related to the C/T dimorphism. In conclusion, the association of the C allele with premature MI, suggests that the TM gene and the C/T dimorphism may be aetiological factors involved in the pathogenesis of MI. Possibly, the Ala455 to Val replacement may affect the function of the TM molecule and the activation of the protein C anticoagulant pathway.


2020 ◽  
Vol 75 (5) ◽  
pp. 490-499
Author(s):  
Yuri Y. Kiryachkov ◽  
Marina V. Petrova ◽  
Bagautdin G. Muslimov ◽  
Sergey A. Bosenko ◽  
Mikhail M. Gorlachev

Background.At the same time, the main effect of the use of this drug is the elimination of the autonomic nervous system dysfunction and sympatholysis. It seems important to search for a method of indications and selection of a dose of dexmedetomidine in intensive care.Aims to improve the clinical effectiveness of the electrophysiological navigation of the prolonged use of dexmedetomidine in patients with brain pathology of various origins.Methods.The study included 83 patients 2050 days after the traumatic brain injury, anoxic damage; consequences of acute disorders of cerebral. 37 patients comprised the 1st intervention group with a clinical course of dexmedetomidine (male 28; female 9; average age 49.62.3 years) and 46 patients comprised the 2nd control group without pharmacological correction with dexmedetomidine (male 23; female 23, average age 512.5 years). Criteria for the inclusion of prolonged infusion of the drug dexmedetomidine (Orion Pharma, Finland) are based on heart rate variability (HRV) indicators characteristic of sympathetic hyperactivity, the target task of titration of doses of dexmedetomidine served as the parameters for achieving normal HRV indicators, the appearance of parasympathetic hyperactivity served as the basis for reducing the dosage of the drug or stopping it of application. HRV parameters were recorded before dexmetomedine infusion-initially, on 13; 45; 910; 1520 days of drug administration.Results.The starting dose of dexmedetomidine with sympathetic hyperactivity in patients was 0.12 to 0.24 g.kg1.hr1(average dose 0.160.01; total 200 mg/day). According to digital data from HRV, the effective dose of dexmedetomidine ED50 was 0.260.03 g.kg1.hr1(total daily 353.835.1 g) and was achieved on day 910 using dexmedetomidine.Conclusions.The protective role of dexmedetomidine with correction of sympathetic hyperactivity based on electrophysiological navigation according to the HRV is reliable in the following indicators: The improvement of consciousness; a significant decrease in the incidence of distress lung syndrome; septic shock; mortality.


2020 ◽  
Vol 8 (3) ◽  
pp. 103-112
Author(s):  
Atefeh SADEGHI SHERMEH ◽  
Majid KHOSHMIRSAFA ◽  
Ali-Akbar DELBANDI ◽  
Payam TABARSI ◽  
Esmaeil MORTAZ ◽  
...  

Introduction: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the world health organization (WHO). Cytokines play important roles in the relationship between the immune system and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and function against TB. Material and Methods: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group. Results: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs (p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups (p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874. Conclusions: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility to DR-TB. However, further investigation is necessary. Keywords: Polymorphism, IFN-γ, IL-10, tuberculosis, drug-resistant tuberculosis


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