Non-Infectious Complications in B-Lymphopenic Common Variable Immunodeficiency.

BACKGROUND AND OBJECTIVE: Common variable immunodeficiency (CVID) is considered the most symptomatic type of inborn errors of immunity in humans. Along with infectious complications, which have numerous consequences, non-infectious complications are also a major challenge among CVID patients. METHODS: All registered CVID patients in the national database were included in this retrospective cohort study. Patients were divided into two groups based on the presence of B-cell lymphopenia. Demographic characteristics, laboratory findings, non-infectious organ involvements, autoimmunity, and lymphoproliferative diseases were evaluated. RESULTS: Among 387 enrolled patients, 66.4% were diagnosed with non-infectious complications; however, 33.6% had only infectious presentations. Enteropathy, autoimmunity, and lymphoproliferative disorders were reported in 35.1%, 24.3%, and 21.4% of patients, respectively. Some complications, including autoimmunity and hepatosplenomegaly, were reported to be significantly higher among patients with B-cell lymphopenia. Among organ involvement, dermatologic, endocrine and musculoskeletal systems were predominantly affected in CVID patients with B-cell lymphopenia. Among autoimmune manifestations, the frequency of rheumatologic, hematologic, and gastrointestinal autoimmunity was reported to be higher compared to other types of autoimmunity independent from the B cell-lymphopenia. Furthermore, hematological cancers, particularly lymphoma, were slightly introduced as the most common type of malignancy. Meanwhile, the mortality rate was 24.5%, and respiratory failure and malignancies were reported as the most common cause of death in our patients without significant differences between the two groups. CONCLUSION: Considering that some of the non-infectious complications might be associated with B-cell lymphopenia, therefore, regular patient monitoring and follow-up along with proper medications (besides immunoglobulins replacement therapy) are highly recommended to prevent further sequels and increase the patients' quality of life.

Prenatal Exposure to L-Citrulline Has Positive Effects on Reflexive Motor Behavior in Newborn Mice.

L-citrulline (L-cit) is a nonessential amino acid that interacts with the veracity of neurotransmitters in the brain and might have a positive effect on fetal growth. However, there is no information about the possible effect of L-cit on reflexive motor behavior. Thus, this study aimed to determine the effects of prenatal exposure to L-cit on reflexive motor behavior in mice offspring. Forty pregnant female mice were allocated into four groups. In the control group, mice received water, while in groups 2-4, female mice orally gavage with L-cit (25, 50, and 100 mg/kg) at 5, 8, 11, 14, and 17 days of gestation (GD). Following delivery, pups were selected, and reflexive motor behaviors were determined using ambulation, hind-limb foot angle, surface righting, hind-limb strength, grip strength, front limb suspension, and negative geotaxis tests. Also, serum Nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were determined. Based on the findings, maternal exposure to L-cit improved ambulation score, hind-limb suspension score, grip strength, and front-limb suspension in offspring (P<0.05). Prenatal exposure to L-cit decreased surface righting, hind-limb foot angle, and negative geotaxis in offspring (P<0.05). L-cit decreased immobility time in forced swimming test (FST), tail suspension test (TST), and increased number of squares crossed in the open field test (OFT) and spending time on rotarod on postpartum mice (P<0.05). L-cit increased serum NO levels (P<0.05). L-cit decreased blood MDA and increased SOD and GPx levels in offspring (P<0.05). Findings revealed that L-cit improves postpartum behaviors in mice and reflexive motor in their pups.

Addition of milk to coffee beverages; the effect on functional, nutritional, and sensorial properties.

To date, there exists a debate on the effect of milk added to coffee infusions/beverages concerning the nutritional quality of coffee and the functional properties of its phenolic compounds. Yet, the full nutritional quality and functional properties of a coffee beverage without a significant negative impact on its sensorial profile are highly desired by the consumers. Negative/masking, positive, and neutral effects of milk on the antioxidant activity and bioavailability of coffee phenolics (particularly, chlorogenic acids) have been reported. Some potential factors including the type and amount of milk added, type of coffee beverage, the composition of both milk (protein and fat) and coffee (phenolic compounds), preparation method, assays used to measure antioxidant properties, and sampling size may account for the various reported findings. Interactions between phenolic compounds in coffee and milk proteins could account as the main responsible aspect for the reported masking/negative impact of milk on the antioxidant activity and bioaccessibility/bioavailability of coffee bioactives. However, considering the interactions between milk components and coffee phenolics, which result in the loss of their functionality, the role of milk fat globules and the milk fat globule membrane can also be crucial, but this has not been addressed in the literature so far.HighlightsIn most cases, milk is added to the coffee beverages in several various ways.Effect of milk on the nutritional/functional properties of coffee is controversial.Enough evidence suggests negative effects of milk addition on properties of coffee.Interactions of coffee phenolics and milk proteins could account as the main aspect.The role of milk fat globules and milk fat globule membrane may also be crucial.

Opportunities and challenges for the nanodelivery of green tea catechins in functional foods.

Green tea, the least processed tea product, is scientifically known for its rich antioxidant content originating from polyphenols, especially catechins. The most potent green tea catechin is epigallocatechin-3-gallate (EGCG), which is responsible for a wide range of health benefits including anticancer, antidiabetics, and anti-inflammatory properties. However, green tea catechins (GTCs) are very labile under both environmental and gastrointestinal conditions; their chemical stability and bioavailability primarily depend on the processing and formulation conditions. Nanocarriers can protect GTCs against such conditions, and consequently, can be applicable for designing nanodelivery systems suitable for GTCs. In this review, the latest findings about both opportunities and limitations for the nanodelivery of GTCs and their incorporation into various functional food products are discussed. The scientific findings so far confirm that nanodelivery of GTCs can be an efficient approach towards the enhancement of their health-promoting effects with a minimal dose, controlled and targeted release, lessening the dose-related toxicity, and the efficient incorporation into functional foods. However, further investigation is yet needed to fully explain the cellular mechanisms of action of GTCs on human health and to elucidate the effect of encapsulation on their bioefficacy using well-designed, systematic, long-term, and large-scale clinical interventions. There also exists a substantial concern regarding the safety of the manufactured nanoparticles, their absorption, and the associated release mechanisms.

Randomized Multiresolution Scanning in Focal and Fast E/MEG Sensing of Brain Activity with a Variable Depth.

We focus on electro-/magnetoencephalography imaging of the neural activity and, in particular, finding a robust estimate for the primary current distribution via the hierarchical Bayesian model (HBM). Our aim is to develop a reasonably fast maximum a posteriori (MAP) estimation technique which would be applicable for both superficial and deep areas without specific a priori knowledge of the number or location of the activity. To enable source distinguishability for any depth, we introduce a randomized multiresolution scanning (RAMUS) approach in which the MAP estimate of the brain activity is varied during the reconstruction process. RAMUS aims to provide a robust and accurate imaging outcome for the whole brain, while maintaining the computational cost on an appropriate level. The inverse gamma (IG) distribution is applied as the primary hyperprior in order to achieve an optimal performance for the deep part of the brain. In this proof-of-the-concept study, we consider the detection of simultaneous thalamic and somatosensory activity via numerically simulated data modeling the 14-20 ms post-stimulus somatosensory evoked potential and field response to electrical wrist stimulation. Both a spherical and realistic model are utilized to analyze the source reconstruction discrepancies. In the numerically examined case, RAMUS was observed to enhance the visibility of deep components and also marginalizing the random effects of the discretization and optimization without a remarkable computation cost. A robust and accurate MAP estimate for the primary current density was obtained in both superficial and deep parts of the brain.

Interleukin-23 receptor gene polymorphisms in Iranian patients with juvenile systemic lupus erythematosus

Introduction and objectives: Considering the possible roles of interleukin-23 receptor (IL-23R) gene in the pathogenesis of juvenile systemic lupus erythematosus (JSLE), the objective of this study was to elucidate whether polymorphisms of the IL23R are associated with susceptibility to JSLE in an Iranian population. Materials and methods: A case-control study on 62 patients with JSLE and 78 healthy controls was performed to investigate the associations of four single nucleotide polymorphisms (SNPs) in IL-23R gene, namely, rs7517847, rs10489629, rs11209026, and rs1343151, with susceptibility to JSLE, using real-time polymerase chain reaction Taqman genotyping technique. Results: Analysis of allele and genotype frequency of four selected SNPs revealed statistically significant positive association between homozygous variant of rs7517847 (TT) (P, 0.02) and T allele at the same position (P, 0.01) with JSLE vulnerability. There was no significant association between other evaluated SNPs and JSLE susceptibility. Conclusion: These findings suggest that particular IL-23R gene variants could affect individual susceptibility to JSLE

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Interleukin-23 receptor gene polymorphisms in Iranian patients with juvenile systemic lupus erythematosus.

INTRODUCTION AND OBJECTIVES: Considering the possible roles of interleukin-23 receptor (IL-23R) gene in the pathogenesis of juvenile systemic lupus erythematosus (JSLE), the objective of this study was to elucidate whether polymorphisms of the IL23R are associated with susceptibility to JSLE in an Iranian population. MATERIALS AND METHODS: A case-control study on 62 patients with JSLE and 78 healthy controls was performed to investigate the associations of four single nucleotide polymorphisms (SNPs) in IL-23R gene, namely, rs7517847, rs10489629, rs11209026, and rs1343151, with susceptibility to JSLE, using real-time polymerase chain reaction Taqman genotyping technique. RESULTS: Analysis of allele and genotype frequency of four selected SNPs revealed statistically significant positive association between homozygous variant of rs7517847 (TT) (P, 0.02) and T allele at the same position (P, 0.01) with JSLE vulnerability. There was no significant association between other evaluated SNPs and JSLE susceptibility. CONCLUSION: These findings suggest that particular IL-23R gene variants could affect individual susceptibility to JSLE.

Zeffiro User Interface for Electromagnetic Brain Imaging: a GPU Accelerated FEM Tool for Forward and Inverse Computations in Matlab.

This article introduces the Zeffiro interface (ZI) version 2.2 for brain imaging. ZI aims to provide a simple, accessible and multimodal open source platform for finite element method (FEM) based and graphics processing unit (GPU) accelerated forward and inverse computations in the Matlab environment. It allows one to (1) generate a given multi-compartment head model, (2) to evaluate a lead field matrix as well as (3) to invert and analyze a given set of measurements. GPU acceleration is applied in each of the processing stages (1)-(3). In its current configuration, ZI includes forward solvers for electro-/magnetoencephalography (EEG) and linearized electrical impedance tomography (EIT) as well as a set of inverse solvers based on the hierarchical Bayesian model (HBM). We report the results of EEG and EIT inversion tests performed with real and synthetic data, respectively, and demonstrate numerically how the inversion parameters affect the EEG inversion outcome in HBM. The GPU acceleration was found to be essential in the generation of the FE mesh and the LF matrix in order to achieve a reasonable computing time. The code package can be extended in the future based on the directions given in this article.

Gill lesions and mortality in common carp (Cyprinus carpio) with a dense bloom of Heterosigma-like algae in Khuzestan province.

BACKGROUND: Widespread common carp (Cyprinus carpio) mortalities have been recorded in Khuzestan province fish farms in recent years. In summer of 2017 two cases of harmful algal bloom were encountered that led to massive mortality in common carp in Khuzestan, Iran. AIMS: The aim of this study was to identify the possible etiologic agent of two mortalities with characteristic symptoms of gill lesions due to harmful algae. METHODS: Water samples were collected and 5 moribund fishes were examined by histophatologic, scanning electron microscopic and PCR examination. RESULTS: In wet smear preparations, a lot of algal cells and fragments, and sloughed, necrotic epithelial cells were observed between the lamellae. In histopathologic examination of gills, hyperplasia, necrosis and algal cells surrounded by hyperplastic cells were seen in tissue sections. No inflammatory cell aggregation was noticed. In scanning electron microscopic examination the algae was found attached to the gill surface (cell diameter: 8.5 ± 4.2 µm) with 2 equal flagella. CONCLUSION: Phytoplankton analysis using direct microscopy and electron microscopy, morphologically resembling Heterosigma was identified, however, in PCR tests, Heterosigma analysis showed negative results, therefore the causative agent was called "Heterosigma-like" algae.

Increased IRF4 expression in isolated B cells from common variable immunodeficiency (CVID) patients

Background: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by low serum levels of immunoglobulins (Igs) and recurrent infection. In most CVID patients, a defect in the differentiation of B cells into plasma cells has been observed. Several factors play an important role in the proliferation and differentiation of B cells, including IRF4 and XBP1 transcription factors. Methods: In the present study we investigated the expression of IRF4 and XBP1 in the B-cells of CVID and healthy controls (HCs). For this purpose, we assessed the expression of IRF4 and XBP1 at both mRNA and protein levels by real time-PCR and flow cytometry, respectively. Results: We found that IRF4 expression was significantly increased in CVID patients compared with controls. Although the XBP1 protein level was lower in patients in comparison to controls, this difference was not significant. Conclusion: Taken together, increased IRF4 expression could be involved in defective functions of B cells in CVID patients

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Increased IRF4 expression in isolated B cells from common variable immunodeficiency (CVID) patients.

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by low serum levels of immunoglobulins (Igs) and recurrent infection. In most CVID patients, a defect in the differentiation of B cells into plasma cells has been observed. Several factors play an important role in the proliferation and differentiation of B cells, including IRF4 and XBP1 transcription factors. METHODS: In the present study we investigated the expression of IRF4 and XBP1 in the B-cells of CVID and healthy controls (HCs). For this purpose, we assessed the expression of IRF4 and XBP1 at both mRNA and protein levels by real time-PCR and flow cytometry, respectively. RESULTS: We found that IRF4 expression was significantly increased in CVID patients compared with controls. Although the XBP1 protein level was lower in patients in comparison to controls, this difference was not significant. CONCLUSION: Taken together, increased IRF4 expression could be involved in defective functions of B cells in CVID patients.

Prevalence of metallo­beta­lactamase producing Acinetobacter baumannii isolated from intensive care unit in tertiary care hospitals.

INTRODUCTION: The emergence of Metallo-beta-lactamase (MBL)-producing Acinetobacter baumannii has become a global concern in nosocomial infections. The aim of this study is to determine the prevalence of MBL producing genes among clinical isolates of A. baumannii from hospitalized patients. METHODS: This study was performed from October 2015 to October 2016 at three teaching hospitals located in Isfahan, Iran. Totally, 100 A-baumannii isolates were collected from clinical specimens and identified as A-baumannii using standard microbiological methods. Antimicrobial susceptibility test was determined by disc diffusion method according to the CLSI. Furthermore, the determination of bla IMP-1, bla IMP-2, bla VIM-1, bla VIM-2and bla SIM-1 was detected by PCR. RESULTS: Totally, Sixty-eight percent (68%) of isolates of A. baumannii were recovered from tracheal aspirate. According to the antibiotic susceptibility pattern, the highest level of resistance was against ciprofloxacin (99%), while among tested antibiotics amikacin (10%) was found to be the most effective. 21%, 4%, 7% and 6% isolates carried bla IMP-1, bla IMP-2, bla VIM-1 and bla VIM-2 genes, respectively. Also, bla SIM-1 was not detected in any of the isolates. CONCLUSION: The results of this study showed high rate of the MBL producing A-baumannii isolates in our region and displayed that MBLs producing A-baumannii strains are emerging threats to ICUs.

Decline in peripheral blood NKG2D+CD3+CD56+ NKT cells in metastatic colorectal cancer patients.

OBJECTIVE: Colorectal cancer (CRC) is one of the main causes of cancer deaths in the world. This cancer can be divided into non-metastatic and metastatic CRC stages. CD3+CD56+ NKT cell subsets are a minor T cell subset in peripheral blood and conduct the killing of tumor cells in direct manner. Little is obvious about levels and surface markers of these cells such as NKG2D in different cancers, especially in CRC. METHODS: We included 15 non-metastatic (low-grade), 11 non-metastatic (high-grade), 10 metastatic colorectal cancer patients and 18 healthy controls. The percentages of CD3+CD56+ NKT cells and NKG2D+CD56+ NKT cells from samples were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs) of samples. RESULTS: We found that there was a significantly lower number of NKG2D+CD3+CD56+ cells in peripheral blood of patients with metastatic colorectal cancer compared with normal controls (77.53 ± 5.79 % vs 90.74 ± 9.84 %; p<0.01). CONCLUSION: The fact that frequency of NKG2D+CD56+ NKT cells was significantly lower in patients with metastatic colorectal cancer compared to healthy controls strengthens the hypothesis that NKT cells can play a substantial role in the protection against human colorectal cancer, and this opens up avenues for novel studies about elucidating the other aspects of tumor surveillance in CRC progression and immunotherapy (Tab. 2, Fig. 2, Ref. 46).

Association of NLRP3 single nucleotide polymorphisms with ulcerative colitis: A case-control study.

BACKGROUND: Ulcerative colitis (UC) is inflammatory bowel disease (IBD), characterized by chronic inflammation episodes within mucosal layer of the intestine mostly affecting colon and rectum. As the role of innate immunity in pathogenesis of disease and important role of NLRP3, the aim of this study is to investigate the association of NLRP3 SNPs with UC in Iranian patients. METHODS: Blood samples from 45 UC patients and 56 healthy subjects were tested for single nucleotide polymorphisms in rs10754558, rs3806265, rs4612666, and rs35829419 of NLRP3 gene, using real-time PCR method. RESULTS: Among the investigated SNPs, "GG" genotype of rs10754558 have been 2.48 times more common among UC patients (P=0.04), while "CG" genotype has indicated protective effect against UC, as more frequently found in healthy subjects. CONCLUSION: Despite no significant association between three investigated SNPs and disease, "GG" and "CG" genotypes of rs10754558 have been significantly associated with disease.

Prevalence of antibiotic resistance and genetic relatedness of Escherichia coli isolates in HIV and thalassemia patients in southeastern Iran.

The present study was carried out to evaluate the prevalence of antibiotic resistance genes in Escherichia coli isolates from HIV and thalassemia patients and to determine the phylogenetic group distribution and to genotype the isolates in southeastern Iran. This cross-sectional study was performed in E. coli isolates taken from fecal and urine samples of 43 HIV and 62 thalassemia patients. The E. coli isolates were examined for 13 antibiotic resistance genes and determine the phylogroups. The Rep-PCR DNA fingerprinting method was utilized to determine the genotype of the isolates. Among the 105 E. coli isolates, 66.7% isolates were positive for qnrS, 55.2% for dhfrI, 40.9% for sulI, 33.3% for sulII and 31.4% for blaTEM genes. A blaCTX-M-15 gene was detected in 20.9% isolates, aac(3)-I in 14.3% isolates and aadA in 12.4% isolates, whereas blaSHV and qnrB genes were identified in 10.5% and 8.6% isolates, respectively. Out of the isolates, only 2.8% isolates possessed the blaOXA-1 gene, and no IMP and VIM genes were detected. The significant phylogroup was A (37.2%), B2 (15.3%), B1 and unknown (each 14.3%), D (13.4%) and C, F and clade I (each 2%). Phylogroup A accounted for the highest antibiotic resistance. The results of Rep-PCR indicated that the isolates were closely related. These results showed a high prevalence of genes encoding antibiotic resistance in the E. coli isolates. The majority of E. coli isolates distributed among phylogroup A, whereas positive isolates for antibiotic resistance genes were disseminated among various phylogroups (A, B2, and D).

Imaging techniques: new avenues in cancer gene and cell therapy.

Cancer is one of the world's most concerning health problems and poses many challenges in the range of approaches associated with the treatment of cancer. Current understanding of this disease brings to the fore a number of novel therapies that can be useful in the treatment of cancer. Among them, gene and cell therapies have emerged as novel and effective approaches. One of the most important challenges for cancer gene and cell therapies is correct monitoring of the modified genes and cells. In fact, visual tracking of therapeutic cells, immune cells, stem cells and genetic vectors that contain therapeutic genes and the various drugs is important in cancer therapy. Similarly, molecular imaging, such as nanosystems, fluorescence, bioluminescence, positron emission tomography, single photon-emission computed tomography and magnetic resonance imaging, have also been found to be powerful tools in monitoring cancer patients who have received therapeutic cell and gene therapies or drug therapies. In this review, we focus on these therapies and their molecular imaging techniques in treating and monitoring the progress of the therapies on various types of cancer.

Immunomodulatory Effects of Adjuvants CPG, MPLA, and BCG on the Derp2-Induced Acute Asthma at Early Life in an Animal Model of BALB/c Mice.

The Th1- and Treg cell-related immune responses play key roles in the modulation of Th2 cell-related allergic disorders. The aim was to evaluate the effects of CPG, MPLA, and BCG on the number of Th1-, Th2-, and Treg cell-related parameters in an animal model of asthma. BALB/c mice were divided into five groups and immunized subcutaneously (SC) on days 1, 15, and 22 with allergen Derp2. Three groups of mice were pretreated SC on days 0, 14, and 21 with CPG, CPG + MPLA, or CPG + BCG. All mice were then challenged intranasally with Derp2 on days 28-37. Blood samples were collected from the retro-orbital sinus, on days 0, 23, and 40. The serum levels of IL-4, IFN-γ, IgE, and IgG2a were measured using ELISA technique. The blood number of Th1 and Treg cells was determined using flow cytometry. At the sensitization phase, the number of Th1 and the serum levels of IFN-γ and IgG2a were significantly increased in the Derp2-sensitized group pretreated with CPG plus MPLA, and the number of Treg cells was significantly elevated in Derp2-sensitized mice pretreated with CPG or CPG plus MPLA as compared with that in Derp2-sensitized control mice. At the challenge phase, the number of Th1 was significantly elevated in Derp2-sensitized mice pretreated with CPG plus MPLA, CPG plus BCG, or CPG; the count of Treg cells was significantly increased in Derp2-sensitized mice pretreated with CPG plus BCG group; and the levels of IFN-γ and IgG2a were significantly enhanced in the Derp2-sensitized group pretreated with CPG plus MPLA in comparison with those in Derp2-sensitized control mice. The scores of inflammation and mucus secretion in the lung were significantly decreased in the Derp2-sensitized group pretreated with CPG, BCG, and CPG plus MPLA in comparison with those in the Derp2-sensitized control group. These results showed that BCG, MPLA, and CPG modulate Th1-, Th2-, and Treg-related parameters and ameliorate lung inflammatory parameters in a mouse model of asthma.

Association of interleukin-1 family gene polymorphisms with juvenile idiopathic arthritis in Iranian population

BACKGROUND: Cytokines, including interleukin-1 (IL-1), seem to contribute towards the pathogenesis of juvenile idiopathic arthritis (JIA), so this study was designed to evaluate the associations of IL-1 gene cluster and IL-1 receptor (IL-1R) gene single nucleotide polymorphisms (SNPs) with JIA proneness in Iranian population. MATERIALS AND METHODS: Genomic DNA of 55 Iranian patients with JIA and 140 controls were extracted and typed for IL-1alpha gene at position −889, IL-1beta gene at positions −511 and +3962, IL-1R gene at position Pst-I 1970, and interleikin-1 receptor antagonist (IL-1Ra) gene at position Mspa-I 11100, using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls. RESULTS: The CC genotype of IL-1Ra at Mspa-I 11100 position was found to be more frequent in patients with JIA compared to healthy individuals (P=0.03), although the CT genotype at the same position was significantly higher in the control group in comparison with patients with JIA (P=0.02). No significant differences were observed between the two groups of case and control for IL-1alpha (−889 C/T), IL-1beta (−511 C/T and +3962 C/T) and IL-1R (Pst-1 1970 C/T). CONCLUSION: The results of the present investigation suggest that certain IL-1Ra gene variants are associated with individuals' susceptibility to JIA. Nevertheless, further studies are required to establish the results of the current study

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Association of tumour necrosis factor-alpha G/A -238 and G/A -308 single nucleotide polymorphisms with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disorder of unknown origin. As proinflammatory cytokines are known to contribute towards the pathogenesis of JIA, this case-control study was performed to examine the associations of certain single nucleotide polymorphisms (SNPs) of tumour necrosis factor-α (TNF-α) gene. Fifty-three patients with JIA participated in this study as patients group and compared with 137 healthy unrelated controls. Genotyping was performed for TNF-α gene at positions -308 and -238, using polymerase chain reaction with sequence-specific primers method. Results of the analysed data revealed a significant positive association for TNF-α gene at positions -308 and -238 for A allele in patients group compared with controls (P < 0.01). At the genotypic level, the frequency of TNF-α gene at positions -308 and -238 for GG genotype was discovered to be higher in the patients with JIA compared to the healthy controls (P < 0.01), while GA genotype at the same positions was observed to be less frequent in the case group than the controls (P < 0.01). At the haplotypic level, a significant positive association for TNF-α GG haplotype (positions -308, -238) together with a notable negative association for TNF-α AG and GA haplotypes at the same positions were detected in the patients group in comparison with the healthy individuals (P < 0.01). Cytokine gene polymorphisms might affect the development of JIA. Particular TNF-α gene variants could render individuals more susceptible to JIA..