Publications by authors named "Mehdi Shekarabi"

23 Publications

  • Page 1 of 1

Discovery of a potential biomarker for immunotherapy of melanoma: PLAC1 as an emerging target.

Immunopharmacol Immunotoxicol 2020 Dec 26;42(6):604-613. Epub 2020 Oct 26.

Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.

Background: Melanoma has increased in incidence worldwide prompting investigators to search for new biomarkers for targeted immunotherapy of this disease. Placenta specific 1 (PLAC1) is a new member of cancer-testis antigens with widespread expression in many types of cancer. Here, we aimed to study for the first time the expression pattern of PLAC1 in skin cancer samples including cutaneous melanoma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) in comparison to normal skin and nevus tissues and potential therapeutic effect of anti-PLAC1 antibody in melanoma cancer cell lines .

Materials And Methods: Polyclonal and monoclonal antibodies were applied for immunohistochemical profiling of PLAC1 expression using tissue microarray. The cytotoxic action of anti-PLAC1 antibody alone or as an antibody drug conjugate (with anti-neoplastic agent SN38) was investigated in melanoma cell lines.

Results: We observed that 100% (39 of 39) of melanoma tissues highly expressed PLAC1 with both cytoplasmic and surface expression pattern. Investigation of PLAC1 expression in BCC ( = 110) samples showed negative results. Cancer cells in SCC samples ( = 66) showed very weak staining. Normal skin tissues and nevus samples including congenital melanocytic nevus failed to express PLAC1. Anti-PLAC1-SN38 exerted a specific pattern of cytotoxicity in a dose- and time-dependent manner in melanoma cells expressing surface PLAC1.

Conclusions: Our findings re-inforce the concept of re-expression of embryonic/placental tissue antigens in cancer and highlight the possibility of melanoma targeted therapy by employing anti-PLAC1 antibodies. The data presented here should lead to the future research on targeted immunotherapy of patients with melanoma.
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http://dx.doi.org/10.1080/08923973.2020.1837865DOI Listing
December 2020

The effect of smoking on latent tuberculosis infection susceptibility in high risk individuals in Iran.

J Immunoassay Immunochem 2020 Sep 16;41(5):885-895. Epub 2020 Aug 16.

Department of Immunology, School of Medicine, Iran University of Medical Sciences , Tehran, Iran.

Tuberculosis has been declared as a global emergency. Latent tuberculosis infection (LTBI) is a state in which host immunity cannot completely eradicate . Cigarette smoke increases the risk of respiratory infections, such a TB, as it has adverse effects on respiratory immune function. In this cross-sectional study, which was performed from 2016 to 2017, 31 patients with newly diagnosed lung cancer, 63 Chronic obstructive pulmonary disease (COPD), 46 with problems in respiratory system, and 40 healthy subjects were studied. Demographic data of all subjects were recorded a questionnaire. IGRAs (Interferon-γ release assays) were used to determine LTBI. We showed that smoking has significant odds ratio for COPD patients (OR: 4.58, 95% CI: 1.93-10.87). Also, the concordance of smoking with COPD (OR: 22, 95% CI: 2.7-179.2), lung cancer (OR: 10, 95% CI: 1.03-97), and other respiratory diseases (OR: 4.54, 95% CI: 1.93-10.87) is a significant risk factor for the presence of LTBI whereas the existence of LTBI in the study groups did not show any significant odds ratio. This study is the first to analyze the relationship between smoking in patients with respiratory diseases and LTBI susceptibility in Iran by IGRAs, which proposes cigarette smoking as a powerful risk factor for LTBI.
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http://dx.doi.org/10.1080/15321819.2020.1806075DOI Listing
September 2020

Role of autophagy in the pathogenesis of rheumatoid arthritis: Latest evidence and therapeutic approaches.

Life Sci 2020 Aug 5;254:117734. Epub 2020 May 5.

Halal Research Center of IRI, FDA, Tehran, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Autophagy is considered as an important intracellular mechanism that degrades cytoplasmic components to furnish additional energy. It has cytoprotective effects through the degradation of intracellular pathogens, damaged organelles, and protein aggregates. On the other hand, there are reports of an association between autophagy and autoimmune diseases. Indeed, it has been evident that autophagy is dysregulated in various autoimmune diseases including rheumatoid arthritis (RA). Autophagy is implicated in the maturation survival and proliferation of various immune and non-immune cells, which play pivotal roles in RA pathogenesis. Additionally, autophagy seems to be involved in citrullination and presentation of citrullinated peptides to T lymphocyte cells. Presentation of citrullinated peptides through MHC compartments to the T cells leads to immune response and chronic inflammation. Evidence suggests that autophagy could be implicated in apoptosis resistance of RA fibroblast-like synoviocyte (RA FLS), osteoclastogenesis, and finally severe bone and cartilage destruction. Since autophagy could be an important phenomenon in RA pathogenesis, we summarized the roles of autophagy in citrullination, osteoclastogenesis, RA FLS cells survival, apoptosis resistance of cells, lymphocyte homeostasis and its clinical outcomes in RA disease.
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http://dx.doi.org/10.1016/j.lfs.2020.117734DOI Listing
August 2020

Evaluating the Immunoreactivity of Ailanthus Altissima (The Tree of Heaven) Pollen Extract in Atopic Patients.

Iran J Allergy Asthma Immunol 2020 Apr 16;19(2):132-138. Epub 2020 Apr 16.

Department of Immunology, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.

IgE-mediated hypersensitivity reaction to pollens is a common health problem in atopic patients. In this regard, the assessment of the allergenicity of highly pollinating plants would be demanding. Based on the increment of Ailanthus altissima (A. altissima) tree in some parts of Iran and considering its probable role in respiratory allergy, in this study, we aimed to investigate its IgE-immunoreactivity and in diagnostic applications. One hundred and twenty-five allergic rhinitis patients who were diagnosed as high IgE responders and demonstrated seasonal rhinitis or rhinoconjunctivitis, as well as 20 healthy controls (HCs) with no allergic symptoms, were enrolled in this study. Total protein extract was prepared from A. altissima pollens and subjected to quality control experiments and finally used in ELISA and western blotting studies. Approximately 24% of the atopic patients (30 from 125) showed positive immunoreactivity to A. altissima extract. The median (IQR) of absorbance (450 nm) of the specific IgE against A. altissima pollen extract in HCs and positive groups were 0.33 (0.28-0.42) and 0.59 (0.36-0.79), respectively (p<0.001). Receiver operating characteristics (ROC) curve analysis of the specific ELISA results, revealed a cut-off value of 0.46 and a sensitivity of 70% and specificity of 100%. Western blotting with the sera positive cases revealed that the main immunoreactive proteins range from 10 to 70 kDa. This study revealed that some of A. altissima pollen proteins ranging from 10 to 70 kDa show IgE-reactivity in atopic patients and may play a role in their allergic reaction symptoms.
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http://dx.doi.org/10.18502/ijaai.v19i2.2763DOI Listing
April 2020

Assessment of miR-181b-5p, miR-23a-3p, BCL-2, and IL-6 in Peripheral Blood Mononuclear Cells of Autistic Patients; Likelihood of Reliable Biomarkers.

Iran J Allergy Asthma Immunol 2020 Feb 1;19(1):74-83. Epub 2020 Feb 1.

Department of Regenerative Medicine, Royan Institute for Stem Cell Biology and Technology, Tehran, Iran.

Autism is a neurodevelopmental disorder that is recognized by stereotypic and repetitive behaviors after 2 years of old. Dysregulation of the immune system, especially inflammation which is mostly regulated by IL-6, imposes a deficit in CNS development. Along with this crucial biomarker, researchers have proposed BCL-2, micro RNA-23a-3p (miR-23a-3p), miR-181b-5p as other probable biomarkers involved in inflammation and apoptosis. The aim of the study was to evaluate the alteration in the expression of these biomarkers in a group of autism spectrum disorder (ASD) children. Peripheral blood mononuclear cells (PBMCs) were obtained from 37 autistic patients. After RNA extraction with precipitation method, the Syber green qReal-time Polymerase Chain Reaction (PCR) was performed in order to evaluate the possible alteration in the expression of IL-6, BCL-2, miR-181b-5p, and miR-23a-3p. The results were compared with healthy controls. IL-6 was significantly upregulated in ASD patients (p=0.003). On the other hand, miR-23a was upregulated and BCL-2 downregulated in ASD patients but the changes were not significant. In initial evaluations, expression changes of miR-181b-5p were not statistically significant. However, when Patients were divided into two groups of upregulated and downregulated, re-evaluation showed that both up- (p=0.005) and down-regulation (p=0.004) (i.e. changes regardless of the direction) of miR-181b were significant in autistic children. IL-6 and miR-181b-5p can have proper diagnostic values and are reliable biomarkers with high sensitivity and specificity. On the other hand, PBMC can be utilized for such studies and also evaluation of patients' condition instead of brain tissue as it is less accessible.
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http://dx.doi.org/10.18502/ijaai.v19i1.2420DOI Listing
February 2020

IL-10 induces TGF-β secretion, TGF-β receptor II upregulation, and IgA secretion in B cells.

Eur Cytokine Netw 2019 09;30(3):107-113

Tehran University of Medical Sciences, Pediatrics Center of Excellence, Children's Medical Center, Research Center for Immunodeficiencies, Tehran, Iran.

Interleukin-10 (IL-10) is a pleiotropic cytokine, which has both regulatory and stimulatory effects on different immune cell types. Different studies have reported the importance of IL-10 and Transforming growth factor-beta (TGF-β) in the regulation of B cell class switching the production of immunoglobulin A (IgA); however, the underlying mechanisms remain to be fully elucidated. The objective of this study was to investigate the TGF-β response during B stimulation of human B cells by IL-10. Pan B cells of healthy donors were negatively purified by a magnetic cell separation technique. B cells were cultured with multimeric CD40 ligand (mCD40L) and IL-10 for two and seven days. After harvesting in specific days, TGF-β receptor II and surface IgA expression was determined by flow cytometry, while IgA and TGF-β secretion was assessed by enzyme-linked immunosorbent assay. B cells endogenously expressed TGF-β receptor II and after 48 hours cultivation with mCD40L or mCD40L plus IL-10, both the expression of this receptor and the production of TGF-β were significantly increased. Notably, TGF-β levels following stimulation with mCD40L and IL-10 were higher than those produced by B cells stimulated with mCD40L alone. Furthermore, at day 7 and following IL-10 stimulation, there was a significant rise in the amount of IgA secretion by class-switched plasma cells, which was higher than stimulation with mCD40L alone. Our findings suggest that IL-10 can modulate TGF-β production and TGF-β receptor expression in mCD40-activated human B lymphocytes.
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http://dx.doi.org/10.1684/ecn.2019.0434DOI Listing
September 2019

The pattern of antiviral protein expression induced by interferon λ1 in peripheral blood mononuclear cells of patients with chronic hepatitis C virus infection.

Arch Virol 2020 Mar 11;165(3):583-592. Epub 2020 Jan 11.

Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.

Interferon lambda was discovered in recent years to be an antiviral agent, and research on different aspects of this antiviral factor in viral infection and investigations of its effectiveness are also progressing. The immunological effects of interferon lambda on different cell populations is not precisely known, which may be due to its use of a heterodimeric receptor consisting of IL-10R2 and IFN-λR1, which are not broadly expressed in all types of cells. In the present study, signaling by interferon lambda and its effect on the expression of hepatitis C virus (HCV) proteins were measured, and the expression pattern of some antiviral proteins and IL-10 levels were investigated in peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from 50 patients with chronic genotype 1a HCV infection and 10 healthy individuals as controls. The PBMCs were treated with various doses of interferon lambda at different times of cultivation. Real-time PCR was used for relative quantification of Mxa, PKR, OAS, ISG15 and HCV core mRNAs. Expression of the NS5A protein was measured by flow cytometry, and IL-10 production was assessed by ELISA. A significant increase in the expression of mRNA encoding antiviral proteins and a decrease in the expression of mRNAs encoding the HCV core protein were observed when cells were treated with interferon lambda in an intermittent manner. The expression of HCV NS5A protein and interleukin 10 levels were also lower than in the control group. It was shown that the maximum antiviral effect of interferon lambda in PBMCs is dependent on the dose and treatment time.
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http://dx.doi.org/10.1007/s00705-019-04438-zDOI Listing
March 2020

The Heterogeneous Pathogenesis of Selective Immunoglobulin A Deficiency.

Int Arch Allergy Immunol 2019 15;179(3):231-246. Epub 2019 May 15.

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran,

Selective immunoglobulin A deficiency (SIgAD) is the most prevalent type of primary immunodeficiency disorder. The phenotypic feature of SIgAD is related to a defect in B lymphocyte differentiation into plasma cell-producing immunoglobulin A (IgA). In this review, we summarize the recent advances in this regard. Genetic (including major histocompatibility complex [MHC] and non-MHC genes), immunologic (including B and T lymphocyte subsets abnormality), cytokines/chemokines and their related receptors, apoptosis and microbiota defects are reviewed. The mechanisms leading to SIgAD are most likely multifactorial and it can be speculated that several pathways controlling B cells functions or regulating epigenetic of the IGHA gene encoding constant region of IgA heavy chain and long-term survival of IgA switched memory B cells and plasma cells may be defective in different SIgAD patients.
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http://dx.doi.org/10.1159/000499044DOI Listing
August 2019

Serum levels of adiponectin and vitamin D correlate with activity of Rheumatoid Arthritis.

Mol Biol Rep 2019 Apr 27;46(2):2505-2512. Epub 2019 Mar 27.

Department of Rheumatology, Iran University of Medical Sciences, Tehran, Iran.

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which numerous cells and mediators affect inflammatory conditions and disease severity. To compare the serum levels of adiponectin, vitamin D, copper, and zinc in patients with RA and to investigate the relationship between these parameters and RA severity. Ninety patients with RA and 30 healthy controls participated in this cross-sectional case-control study between November 2016 and April 2017; according to the ACR/EULAR criteria for RA. Serum levels of adiponectin were determined by ELISA; copper and zinc by colorimetric spectrophotometry; and vitamin D by HPLC. Kruskal-Wallis and Spearman tests were performed using SPSS software and data were depicted by GraphPad Prism software. Compared with healthy controls, the serum level of adiponectin was significantly increased, whereas vitamin D was significantly decreased in patients with RA. Adiponectin and vitamin D levels were inversely correlated in RA subgroups (P < 0.001, r = - 0.410). Adiponectin and vitamin D correlated with RA severity. Furthermore, no significant difference was found in copper and zinc levels between RA groups and controls. The definitive roles of adiponectin, vitamin D, copper, and zinc are not completely determined in RA development. Based on disease activity, these parameters can modulate inflammatory conditions, thus they have the potential to be used as promising therapeutic biomarkers to follow up the severity of disease, as well as the progression and treatment success in patients with RA.
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http://dx.doi.org/10.1007/s11033-019-04682-1DOI Listing
April 2019

Differential serostatus of Epstein-Barr virus in Iranian MS patients with various clinical patterns.

Med J Islam Repub Iran 2018 27;32:118. Epub 2018 Nov 27.

Department of Neurosciences, Tehran University of Medical Sciences, Tehran, Iran.

Epidemiological evidence suggests a role of Epstein-Barr virus (EBV) in triggering the pathogenesis of Multiple Sclerosis (MS). The aim of this study was to assess the EBV-specific antibodies in MS patients with various clinical patterns and their association with the production of IFN-γ, IL-12, and IL-4 cytokines compared with healthy individuals. We measured EBNA-1 IgG, VCA IgG, and production of IFN-γ, IL-12 and IL-4 cytokines in patients with different clinical patterns and healthy controls using ELISA method. There was a higher titer of anti-EBV antibodies in MS patients compared to healthy controls. SPMS patients generated higher EBNA-1 levels than those with RRMS and PPMS patients whereas; the level of VCA IgG was higher in the RRMS patients than PPMS. In PPMS patients, a significant increase was found in IFN-γ and IL-12 cytokines compared to other subtypes, whereas IL-4 cytokine had a decreased level compared to RRMS patients. Higher anti-EBV antibodies are associated with increased IL-12 cytokine in RRMS patients. However, no significant correlation was found between these antibodies and other secreted cytokines. EBV infection is one of the strong risk factors for MS. Acting on these factors could be useful to decrease the incidence and disease exacerbation of MS. Study of the antibody levels to EBV virus could be useful for evaluating MS risk score in each clinical subtypes.
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http://dx.doi.org/10.14196/mjiri.32.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387825PMC
November 2018

Characterization of CD4+ and CD8+ T Cell Subsets and Interferon Regulatory Factor 4 (IRF4) in MS Patients Treated with Fingolimod (FTY-720): A Follow-up Study.

Iran J Allergy Asthma Immunol 2018 Aug 12;17(4):346-360. Epub 2018 Aug 12.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Fingolimod is a novel immunomodulatory drug used in patients with relapsing multiple sclerosis (MS) which reversibly inhibits egress of lymphocytes from lymph nodes. In this longitudinal study, the frequency of Interferon- gamma (IFN-γ)+, IL4+, IL17+ and IL10+ CD4+ and CD8+ T cell subsets were measured in Fingolimod treated patients before and after 12 months'(12M) therapy using flow cytometry and compared to those of naive, Betaferon treated MS patients and healthy individuals. Additionally, the level of transcription factor IRF4 and IL-6, IL-23, TGF-β1 cytokines, required for differentiation of IL-17+ T cells, were assessed by RT-PCR and ELISA, respectively. In Fingolimod treated MS patients, we observed a significant decrease in the percentage of IFN-γ+/IL17+ CD4+ and CD8+ T cell subsets. In contrast, Fingolimod increased IL10+ CD4+ T cells. We also showed that IFN-γ+IL17+ co-producing CD8+ T cells were reduced in patients under fingolimod therapy. furthermore, Fingolimod could reduce the expression level of IRF4 in patients while IL6 was increased in the supernatant of cultured peripheral blood mononuclear cells. Our data showed that Fingolimod treatment alters CD4+ and CD8+ T cell subsets and reduces expression of IRF-4, which affects the proportion of pathogenic memory T cells in peripheral blood.
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http://dx.doi.org/10.18502/ijaai.v17i4.94DOI Listing
August 2018

Elevated expression of miR-21 and miR-155 in peripheral blood mononuclear cells as potential biomarkers for lupus nephritis.

Int J Rheum Dis 2019 Mar 5;22(3):458-467. Epub 2018 Nov 5.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Aim: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). There is a great interest in using microRNAs (miRNAs) as diagnostic and prognostic biomarkers in autoimmune diseases.

Materials And Methods: This study evaluated miR-16, miR-21, miR-141, miR-146a, and miR-155 expression levels in peripheral blood mononuclear cells (PBMCs) of 55 female SLE patients with absent, inactive, or active nephritis, and 30 healthy controls (HCs) using quantitative polymerase chain reaction.

Results: MiR-21 and miR-155 levels were significantly greater in the active nephritis group than in the absent, inactive or HC groups. Moreover, receiver operating characteristic and logistic regression analyses revealed miR-21 and miR-155 were significant risk factors for LN.

Conclusion: Overexpression of miR-21 and miR-155 in PBMCs may participate in LN pathophysiology and these miRNAs could be used as biomarkers for the condition.
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http://dx.doi.org/10.1111/1756-185X.13410DOI Listing
March 2019

Frequency of CD4 and CD8 T cells in Iranian chronic rhinosinusitis patients.

Allergy Asthma Clin Immunol 2018 5;14:47. Epub 2018 Jul 5.

1Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Chronic Rhinosinusitis (CRS) is a persistent inflammatory disease affecting paranasal sinuses. CRS is categorized into two distinct subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Although several immune cells are involved in the CRS pathogenesis, the role of T cells is not fully understood. The objective of the present study was to evaluate the frequency of CD4 and CD8 T cells and macrophages in the sinonasal mucosa of CRS patients, as well as to investigate the specific transcription factors for Th1, Th2, Th17, and Treg cells.

Methods: In this study, 15 healthy controls, 12 CRSsNP, and 23 CRSwNP patients participated. CD4, CD8, and CD68 cells were investigated in the sinonasal tissues using immunohistochemistry. The expression of transcription factors related to Th subsets (T-bet, GATA3, Ror-γt, and FoxP3) was evaluated using real-time PCR. Furthermore, CRSwNP patients were defined as eosinophilic when eosinophils consisted of more than 10% of total inflammatory cells. The Kruskal-Wallis, Mann-Whitney, and Spearman tests were used in statistical analyses.

Results: The median (range) age of the studied groups was: 32 (14-67) for CRSwNP, 28 (10-43) for CRSsNP, and 27 (17-44) for controls. The number of eosinophils in CRSwNP patients was higher than two other groups, whereas neutrophils were elevated in both CRSwNP and CRSsNP groups in comparison to controls. The frequency of CD4 and CD8 T cells, macrophages, and total inflammatory cells were significantly increased in CRSwNP and CRSsNP patients compared with controls. The mRNA expression of GATA3 was increased in CRSwNP patients while mRNA expression of Ror-γt was elevated in CRSsNP patients. No significant difference was observed in T-bet mRNA expression among three groups. Both CRSwNP and CRSsNP patients showed decreased FoxP3 mRNA expression in comparison to controls.

Conclusion: The frequency of CD4 and CD8 T cells was elevated in CRS patients. In addition, we demonstrated Th2 dominance in CRSwNP patients and Th17 dominance in CRSsNP patients, implicating different mechanisms may underlie the disease. Better CRS classification and targeted therapeutic strategies may be achievable by determining the pattern of infiltrating inflammatory cells. Therefore, further experimental investigations on T cells are needed.
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http://dx.doi.org/10.1186/s13223-018-0270-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034261PMC
July 2018

The Relationship between insulin variable number of tandem repeats (INS-VNTR) -23 A/T and cytotoxic Tlymphocyte associated protein-4 (CTLA-4) +49 A/G polymorphisms with islet autoantibodies in persons with diabetes.

Med J Islam Repub Iran 2017 12;31:83. Epub 2017 Dec 12.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran & Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran.

Both genetic and environmental factors are important in pathogenesis of diabetes. Non HLA (Human Leukocyte Antigen) genes such as INS-VNTR and CTLA-4 in addition of HLA genes have influence on genetic susceptibility for diabetes mellitus. In this study the association of +49 A/G CTLA-4 and -23 A/T INS-VNTR polymorphisms with diabetes and their association with islet autoantibodies were investigated. Thirty four autoantibody positive adult persons with diabetes mellitus and 39 persons with Type 1diabetes mellitus (T1DM), 40 autoantibody negative Type 2 diabetes mellitus (T2DM) patients and 40 healthy controls were studied using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique. The frequencies of -23 A/T INS-VNTR genotypes were not significantly different among study groups. It was shown that the distribution of the +49A/G CTLA-4 allele and genotype frequencies did not differ between T1DM patients, autoantibody positive adult patients and controls. With increasing CTLA-4 G allele and GG/AG genotypes, the frequency of Glutamic Acid Decarboxylase Autoantibody (GADA), Islet Cell Autoantibody (ICA) and Islet Antigen 2 Antibody (IA2A) positive patients were increased. Our results suggest that susceptibility allele A of -23A/T INS-VNTR does not have any role in the pathogenesis of diabetes in our patients and susceptibility allele G of +49 A/G CTLA-4 if not, has a small role in pathogenesis of diabetes in T1DM and autoantibody positive adult patients and in spite of significant increase in autoantibody negative T2DM group it does not have any role in disease pathogenesis.
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http://dx.doi.org/10.18869/mjiri.31.83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014810PMC
December 2017

Effects of Oral Probiotic Feeding on Toll-Like Receptor Gene Expression of the Chicken's Cecal Tonsil.

Rep Biochem Mol Biol 2018 Apr;6(2):151-157

Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background: It was proposed that probiotics may influence immune system through direct or indirect exposure. Direct exposure is mostly mediated by surface receptors. Toll-like receptors (TLRs) are conserved molecular sensors which could be triggered via some pathogen associated structures, hence, modulate the immune responses. This study was conducted to elucidate the impact of lactobacillus acidophilus as a common probiotic on the expression level of TLRs in the chicken's cecal tonsil.

Methods: Thirty one-day-old chicken were selected and separated into three groups as probiotic-fed, dairy-fed and control. In addition to commercial powder supply, each chicken in the probiotic-fed group received 109 CFU/Kg of L. acidophilus daily. While, chickens in the dairy-fed group were provided with commercial powder feed and sterile dairy milk. After 14 and 21 days of oral feeding the cecal tonsil was removed and the expression of TLR2, TLR4 and TLR5 were examined by real-time PCR.

Results: At the age of 14-day, there was a slight upregulation in the expression levels of TLR2 (118.9%), TLR4 (129.6%) and TLR5 (123.7%) of the cecal tonsil in the probiotic-fed group; however, these alterations were not statistically significant. At the age of 21-day, a non-significant downregulation was observed in TLR expression level of both dairy-fed (TLR2, 85%; TLR4, 79.5%; and TLR5, 86.5%) and probiotic-fed (TLR2, 88.8%; TLR4, 81%; and TLR5, 87.2%) groups in comparison to controls.

Conclusion: The findings revealed that although the probiotic supplementation could be useful but it did not significantly affect innate immunity state through alteration of TLRs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941120PMC
April 2018

Otitis Media with Effusion in Children and the Impact of Risk Factors on Serum Cytokine Levels.

Iran J Otorhinolaryngol 2017 Mar;29(91):75-81

ENT and Head and Neck Research Center and Department   , Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences,Tehran,Iran.

Introduction: To evaluate the role of allergic-type and infectious-type cytokines in children with chronic otitis media with effusion (OME).

Materials And Methods: We investigated serum levels of interleukins (IL)-4, IL-5, and IL-13, along with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), by enzyme-linked immunosorbent assay (ELISA) in 35 children with OME and 28 healthy controls.

Results: Children with OME had significantly higher levels of IL-5 in comparison with the control group, ranging from 1 pg/ml in cases to 0.04 pg/ml in controls (P=0.009). However, after adjusting for confounding variables, there was no significant difference in serum levels of IL-13, IL-4, IFN-γ, or TNF-α between the two groups (P=0.287, P=0.627, P=0.793, and P=0.217, respectively).

Conclusions: The findings of this study suggest that in comparison with the control group, serum IL-5 levels were elevated in OME cases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380392PMC
March 2017

Th1 and Th2 cytokine gene expression in atopic and nonatopic patients with nasal polyposis.

Ear Nose Throat J 2015 Jun;94(6):228-35

ENT Research Center, Iran University of Medical Science, Tehran, Iran.

The pathogenesis of nasal polyps has been debated for many years. The lymphocytes that infiltrate nasal polyps have been identified as predominantly memory T cells in an activated state, and these cells produce a mixed cytokine pattern of T1 helper (Th1) and T2 helper (Th2) cells. We conducted a prospective study to compare the expression levels of some Th1 and Th2 cytokines in atopic and nonatopic patients. Our study population consisted of 75 adults-42 men and 33 women (mean age: 38 yr)-with nasal polyposis. Patients with an allergy were distinguished from those without an allergy on the basis of the history, the results of skin-prick testing, and measurement of total IgE serum concentrations. Based on these criteria, patients were divided into two groups: atopic (n = 38) and nonatopic (n = 37). Levels of cytokine gene expression in the atopic patients were compared with those of the nonatopic patients by real-time polymerase chain reaction. Statistical analysis found no significant differences in the rate of interleukin (IL) 10 and IL-12 gene expression between the allergic and nonallergic patients. On the other hand, rates of interferon gamma and IL-4 gene expression were significantly higher in the atopic patients (p = 0.03 and p = 0.02, respectively). Our research suggests that an imbalance of Th1 and Th2 cells plays an important role in the pathophysiology of nasal polyps. Although nasal polyposis is a multifactorial disease associated with several different etiologic factors, chronic persistent inflammation is undoubtedly a major factor, regardless of the specific etiology.
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http://dx.doi.org/10.1177/014556131509400608DOI Listing
June 2015

Study of NGEP expression in androgen sensitive prostate cancer cells: A potential target for immunotherapy.

Med J Islam Repub Iran 2015 13;29:159. Epub 2015 Jan 13.

Professor, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran, Department of Medical Biotechnology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran & Food and Drug Laboratory, Fardis, Alborz, Iran.

Background: Prostate cancer is one of the leading causes of cancer deaths among men. New gene expressed in prostate (NGEP), is a prostate-specific gene expressed only in normal prostate and prostate cancer tissue. Because of its selective expression in prostate cancer cell surface, NGEP is a potential immunotherapeutic target. To target the NGEP in prostate cancer, it is essential to investigate its expression in prostate cancer cells.

Methods: In the present study, we investigated NGEP expression in LNCaP and DU145 cells by real time and RT-PCR, flow cytometric and immunocytochemical analyses.

Results: Real time and RT-PCR analyses of NGEP expression showed that NGEP was expressed in the LNCaP cells but not in DU145 cells. The detection of NGEP protein by flow cytometric and immunocytochemistry analyses indicated that NGEP protein was weakly expressed only in LNCaP cell membrane.

Conclusion: Our results demonstrate that LNCaP cell line is more suitable than DU145 for NGEP expression studies; however, its low-level expression is a limiting issue. NGEP expression may be increased by androgen supplementation of LNCaP cell culture medium.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431361PMC
May 2015

Study of NGEP expression pattern in cancerous tissues provides novel insights into prognostic marker in prostate cancer.

Biomark Med 2015 ;9(4):391-401

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Aim: The aim of this study was to produce a novel polyclonal antibody against extracellular domain of NGEP protein and explore its role in prognosis of prostate cancer.

Materials & Methods: Polyclonal antibodies against two peptides (NGEP-p1 and NGEP-p2) derived extracellular domains of NGEP were prepared and the intensity and distribution of NGEP expression analyzed in large series of prostate tissue specimens.

Results: We found a significant inverse correlation between NGEP expression and prognostic features such as Gleason score, pathologic tumor stage and prostate-specific antigen level using anti-NGEP-p2 antibody.

Conclusion: The results indicate that the high level of expression could be associated with good prognosis in prostate cancer. However, additional studies are required to evaluate NGEP as an independent prognostic factor for prostate carcinoma.
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http://dx.doi.org/10.2217/bmm.14.106DOI Listing
January 2016

Reduced expression of NGEP is associated with high-grade prostate cancers: a tissue microarray analysis.

Cancer Immunol Immunother 2013 Oct 17;62(10):1609-18. Epub 2013 Aug 17.

Immunology Research Centre, Iran University of Medical Sciences, Tehran, Iran.

New gene expressed in prostate (NGEP) is a newly diagnosed prostate-specific gene that is expressed only in normal prostate and prostate cancer cells. Discovery of tissue-specific markers may promote the development of novel targets for immunotherapy of prostate cancer. In the present study, the staining pattern and clinical significance of NGEP were evaluated in a series of prostate tissues composed of 123 prostate cancer, 19 high-grade prostatic intraepithelial neoplasia and 44 samples of benign prostate tissue included in tissue microarrays using immunohistochemistry. Our study demonstrated that NGEP localized mainly in the apical and lateral membranes and was also partially distributed in the cytoplasm of epithelial cells of normal prostate tissue. All of the examined prostate tissues expressed NGEP with a variety of intensities; the level of expression was significantly more in the benign prostate tissues compared to malignant prostate samples (P value <0.001). Among prostate adenocarcinoma samples, a significant and inverse correlation was observed between the intensity of NGEP expression and increased Gleason score (P = 0.007). Taken together, we found that NGEP protein is widely expressed in low-grade to high-grade prostate adenocarcinomas as well as benign prostate tissues, and the intensity of expression is inversely proportional to the level of malignancy. NGEP could be an attractive target for immune-based therapy of prostate cancer patients as an alternative to the conventional therapies particularly in indolent patients.
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http://dx.doi.org/10.1007/s00262-013-1463-1DOI Listing
October 2013

Septic versus inflammatory arthritis: discriminating the ability of serum inflammatory markers.

Rheumatol Int 2013 Feb 25;33(2):319-24. Epub 2012 Mar 25.

Infectious Disease Department, Pediatric Infectious Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Early diagnosis of septic arthritis is very important. Few studies showed diagnostic accuracy of serum inflammatory markers in septic arthritis. The aim of our study was to compare the serum and synovial fluid markers [procalcitonin, serum IL-6, TNF-α, C-reactive protein, erythrocyte sedimentation rate, synovial fluid white blood cell counts and PMN percentage] in septic and inflammatory arthritis. Seventy-five patients, including 25 and 50 septic and non-septic arthritis, were enrolled in the study. The serum and synovial fluid markers [procalcitonin, serum IL-6, TNF-α, C-reactive protein, erythrocyte sedimentation rate, synovial fluid white blood cell counts, and PMN percentage] were compared in septic and inflammatory arthritis. Patients with septic arthritis had significantly elevated levels of procalcitonin, serum TNF-α, C-reactive protein, erythrocyte sedimentation rate, synovial fluid white blood cell counts, and PMN percentage in comparison with the inflammatory arthritis group (P < 0.00). Serum IL-6 level does not differ among the two groups. In a receiver operating characteristic curve analysis, synovial fluid WBC counts, PMN percentage, TNF-α, ESR, and serum PCT preformed best in distinguishing between septic and non-septic arthritis. Our study suggests that PCT can be used to diagnose the septic arthritis, but more studies warranted in order to determine the specificity and sensitivity of the test.
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http://dx.doi.org/10.1007/s00296-012-2363-yDOI Listing
February 2013

Comparing the performance of QuantiFERON-TB Gold and Mantoux test in detecting latent tuberculosis infection among Iranian health care workers.

Int J Occup Med Environ Health 2011 Dec 16;24(4):359-66. Epub 2011 Nov 16.

Antimicrobial Resistance Research Center, Infectious Diseases Department, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: The risk of transmission of Mycobacterium tuberculosis from patients with tuberculosis to health care workers (HCWs) has been well documented but little is known about the prevalence of latent tuberculosis infection (LTBI) in Iranian HCWs. The aim of this study was to determine the prevalence of LTBI among HCWs by using IFNgamma-release assay and compare the results with those of tuberculin skin test (TST).

Methods: Two hundred HCWs were evaluated with both TST and QuantiFERON-TB Gold In Tube test (QFT-GIT). The obtained data were analyzed by SPSS v.16 Software.

Results: The participants were 73 males and 127 females with the mean age of 34.36±8.26 years. TST was positive in 105 cases (52.5%) and the QFT results were positive in 17 cases (8.5%). There was poor agreement between the two tests (53%, κ = 0.115). Induration diameter of TST ≥ 10 mm and working duration ≥ 10 years were independent predictors for positive QFT (p = 0.004).

Conclusions: Due to the fact that BCG vaccination has been administered routinely to all HCWs in Iran, specific tests should be introduced for high risk groups. QFT thus seems to be more effective for LTBI diagnosis than TST among HCWs with BCG immunization history.
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http://dx.doi.org/10.2478/s13382-011-0046-7DOI Listing
December 2011

Characterization of Molecular Evolution in Multi-Drug Resistant of Mycobacterium tuberculosis by rpoB Gene in Patient with Active Pulmonary Tuberculosis from Iranian Isolates.

Int J Biomed Sci 2009 Dec;5(4):326-35

Department of Microbiology and Biology, Islamic Azad University, Parand Branch, Tehran, Iran; ; Department of Clinical Microbiology, Masoud Laboratory, Tehran, Iran;

This is the first genetic biodiversity study of Mycobacterium tuberculosis in Iran. Thus, we investigated the genetic patterns of strains isolated in the first survey of anti-tuberculosis drug-resistance by rpoB gene as part of the Global Project of Anti-tuberculosis Drug Resistance Surveillance (IAU, Iran). A 411-bp fragment of the rpoB gene, containing the sequence of the 81-bp rpoB fragment, was amplified by PCR and the rpoB gene fragments of tuberculosis strains were sequenced using the Amersham auto sequencer. For analysing tree evolution used method UPGMA and Neighbour-Joining. Clinical isolates (34/163) were analyzed by using sequencing gene rpoB and genotyped by program MEGA. The results were compared with the international database. Multi-drug resistant (MDR) was 14% in never treated patients and 8% in previously treated patients. Mutations in rpoB gene and katG genes were detected in 95% and 84% of the MDR strains, respectively. Two clusters were found to be identical by the four different analysis methods, presumably representing cases of recent transmission of MDR tuberculosis. The other strains are divided into 2 groups: group A - similar to the standard and Eastern strains (China, Taiwan) and group B - strains of another genotype. They are grouped separately on the dendrogram and became prevalent in Iran (they are called Iranian residential strains). This study gives a first overview of the M. tuberculosis strains circulating in Iran during the first survey of anti-tuberculosis drug-resistance. It may aid in the creation of a national database that will be a valuable support for further studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614805PMC
December 2009