[Show abstract][Hide abstract] ABSTRACT: The role of transforming growth factor (TGF)-β1, interferon (IFN)-γ, interleukin (IL)-2, IL-3, and IL-6 in the pathogenesis of Alzheimer's Disease (AD) has long been reported in literature. In this case-control study, the concentrations of these cytokines in altered T lymphocytes, as well as serum vitamin B12, have been compared in terms of factors such as, age, the clinical course and the patients' disease risk. 40 patients who met the DSM-IV-TR criteria of AD were selected and an age- and gender-matched control group was recruited. The participants' cognitive performance was measured according to the Mini Mental State Examination (MMSE), the Global Deterioration Scale (GDS) and Clinical Dementia Ratio (CDR). The levels of cytokines were measured in supernatants of lymphocytes culture, using assays of ELISA and atomic absorption. Higher levels of IL-6 and IFN-γ were found more in the altered T lymphocytes of the AD patients rather than in the control individuals. Furthermore, a marginal significant difference was found between the TGF-β levels of the two study groups. Regression analysis of CDR score and cytokines showed the inverse significant correlation between CDR score and IFN-γ levels. Furthermore, the relation between MMSE scores and IFN-γ was significant, meaning that by increasing MMSE score, IFN-γ level was significantly increased. This study suggests that the levels of IL-6 and IFN-γ are significantly increased in altered T lymphocytes of AD patients, as compared to those who are not inflicted with AD, and that they are related to the patient's age. Also, IFN-γ is related to the severity stage of the AD.
Full-text · Article · Dec 2014 · Iranian journal of allergy, asthma, and immunology
[Show abstract][Hide abstract] ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a third leading cause of death.
In this case control study, we prepared 5 cc bloods from the antecubital vein of 100 COPD patients and 40 healthy individuals as control group. Vascular endothelial growth factor (VEGF) expression protein level was measured by ELISA in both groups.
We found that concentration of VEGF in blood serum of patients with COPD (189.9±16pg/ml) was significantly higher than the control group (16.4±3.48pg/ml) (p<0.001). While VEGF serum level in emphysematous patients wasn't significantly different with control group (p=0.07). Furthermore VEGF serum level in COPD patients was proportionally increased with severity of disease (p<0.001). Besides all COPD patients, regardless of their smoking status, were experienced significantly higher levels of VEGF than healthy ones (p=0.001; z=4.3).
Our results suggest VEGF serum concentration as the sensitive index for severity and activity of COPD and its prognosis.
Preview · Article · Aug 2014 · Medical journal of the Islamic Republic of Iran
[Show abstract][Hide abstract] ABSTRACT: Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections and increased susceptibility to malignancies, lymphoproliferative and autoimmune conditions. National registries of PID disorders provide epidemiological data and increase the awareness of medical personnel as well as health care providers.
This study presents the demographic data and clinical manifestations of Iranian PID patients who were diagnosed from March 2006 till the March of 2013 and were registered in Iranian PID Registry (IPIDR) after its second report of 2006.
A total number of 731 new PID patients (455 male and 276 female) from 14 medical centers were enrolled in the current study. Predominantly antibody deficiencies were the most common subcategory of PID (32.3 %) and were followed by combined immunodeficiencies (22.3 %), congenital defects of phagocyte number, function, or both (17.4 %), well-defined syndromes with immunodeficiency (17.2 %), autoinflammatory disorders (5.2 %), diseases of immune dysregulation (2.6 %), defects in innate immunity (1.6 %), and complement deficiencies (1.4 %). Severe combined immunodeficiency was the most common disorder (21.1 %). Other prevalent disorders were common variable immunodeficiency (14.9 %), hyper IgE syndrome (7.7 %), and selective IgA deficiency (7.5 %).
Registration of Iranian PID patients increased the awareness of medical community of Iran and developed diagnostic and therapeutic techniques across more parts of the country. Further efforts must be taken by increasing the coverage of IPIDR via electronically registration and gradual referral system in order to provide better estimation of PID in Iran and reduce the number of undiagnosed cases.
Full-text · Article · Mar 2014 · Journal of Clinical Immunology
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the impact of thromboangiitis obliterans (TAO) sera on activation of primary cultures of human umbilical vein endothelial cells (HUVECs) as a model for vascular endothelial cells.
Study subjects included 21 TAO patients as the case group and 20 healthy smokers and 17 healthy non-smokers as control groups. Case and control groups were matched based on their age, socioeconomic status and smoking habit. HUVECs were incubated with the sera of case and control groups and gene expression of intercellular adhesion molecule (ICAM-1) and vascular adhesion molecule (VCAM-1) were evaluated by real-time polymerase chain reaction, TaqMan method.
The expression of ICAM-1 and VCAM-1 were significantly higher in HUVECs after incubation with TAO sera compared to control groups (P < 0.05). VCAM-1 had a significant correlation with duration of smoking (P < 0.001, R = 0.672), while the expression of ICAM-1 had a significant correlation with the number of cigarettes smoked daily (P = 0.04, R = 0.421).
Sera from TAO patients could activate HUVECs. This same activation might occur in vivo by the responsible cytokines, in particular those released from activated platelets, free oxygen radicals, and possibly low levels of nitric oxide (NO) of the sera of TAO patients, as a consequences of chronic cigarette smoking and of endothelial NO synthase polymorphism. Therefore, plasma exchange might be helpful in acute phase of the disease for saving the limbs and administration the combinations of exogenous NO with anti-oxidants might be helpful in long-term management of TAO patients to reduce the risk and rate of amputation.
Full-text · Article · Jan 2014 · International Journal of Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: Preeclampsia is the most common serious disorder during pregnancy and studies show several immune-related processes in its pathophysiology. The role of cytokines and their expression remains controversial in this field. One of the cytokines of interest in recent studies has been TNF-α, which has been shown to have a higher level in maternal plasma of preeclamptic women.
This study was designed to evaluate the role of TNF-α polymorphism at position -238 in the risk of developing preeclampsia during pregnancy.
One hundred fifty three preeclamptic cases and 140 healthy pregnant women were retrieved from two major hospitals of Mashhad, Iran. Methods a case-control study were designed. Anyone with a history of inflammatory disease, hypertension, or chronic kidney disease was excluded. DNA was extracted from peripheral blood leukocytes. Both groups were genotyped for the polymorphism of the TNF-α gene at position -238 by the RFLP method with Ava II enzyme. Allele and genotype frequencies were compared using one-way ANOVA and the Fisher's exact test.
There were significant differences between the two groups in TNF-α genotype at position -238 (P < 0.001). In the preeclamptic group, the frequency of the AA genotype was higher (P < 0.001) and the frequency of the GG genotype was lower (P < 0.001). The overall prevalence of the A allele at position -238 was higher in preeclamptic cases (P < 0.001).
In this study group, TNF-α -238 polymorphism was shown to be different in preeclamptic and non-preeclamptic pregnant women. The AA genotype and the A allele may carry an increased risk for developing of preeclampsia.
[Show abstract][Hide abstract] ABSTRACT: Background: Allergen immunotherapy involves the administration of gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure. This study evaluated the clinical efficacy of immunotherapy with extracts of common aeroallergens North-East of Iran in asthma and allergic rhinitis. Material and Methods: In this prospective study 156 cases were chosen randomley. The mean age of patients was 37 years (range 5-65 years). The patients with mild to moderate asthma and allergic rhinitis and history of atopy were selected for immunotherapy when they showed no effective response to medical treatment.Immunotherapy materials were made from common aeroallergens in north-eastern region of Iran by Dome Hollister US company. Immunotherapy schedule for injection of the extract with vial dilution of 1:10000pg was one injection every week for ten weeks and one injection with dilution of 1:1000pg every other week for the other ten weeks and one injection monthly from dilution of 1:100pg for two years. Results: One hundred twenty (77%) of cases had allergic rhinitis 29(18.5%) cases had allergic asthma and 7(4.5%) cases were mixed. Mean age of patients were 37 years old. 48(30.8%) cases were male. Analysis of efficacy of treatment showed that immunotherapy significantlyimproved the signs and symptoms of all the groups. In allergic rhinitis group 84(70%) cases completely improved, 22(18.4%) patients moderately responded and no response to immunotherapy was observed in 14(11.6%) patients. In allergic asthma group, 22(75%) cases completely improved 4(13.6%) cases moderately responded and no response to immunotherapy was detected in 3(11.4%) cases. In mixed group, 3(42.8%) cases completely improved, 3(42.8%) cases moderately responded and no response was observed in 1(14.4%) case. Conclusion: Specific allergen immunotherapy for patients with allergic persistent mild to moderate asthma and moderate to severe allergic rhinitis without good response to medical treatment is highly recommended. It is recommended as effective treatment in such patients.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the expression of the cytokines, chemokines and effective molecules of peripheral blood mononuclear cells (PBMCs) that play a role in neovascularization in thromboangiitis obliterans (TAO). Lymphocytes from TAO patients (n = 20) and control subjects (healthy smokers [n = 16] and non-smokers [n = 17]) were evaluated using realtime polymerase chain reaction in order to examine the mRNA expression of CXCL1 and interleukin 8 (IL-8; inducers of collateral development by recruitment of circulating progenitor cells [CPCs]), endothelial cell growth factor A (VEGF-A) and inducible nitric oxide synthase (iNOS; inducers of angiogenesis) and interferon gamma (IFN-γ) and vascular endothelial growth factor receptor 1 (VEGFR-1; inhibitors of angiogenesis). CXCL1 expression was significantly higher in the TAO patients than control subjects. The expressions of IL-8, VEGFR-1 and IFN-γ were significantly higher in the TAO patients and smokers than in non-smokers. However, no differences in iNOS and VEGF-A expression were noted. In conclusion, PBMCs from TAO patients expressed cytokines that potentially recruit CPCs and promote arteriogenesis. However, TAO patients typically have low CPC levels, perhaps due to high oxidative stress. Further studies are recommended in order to investigate the efficacy of antioxidant therapy on the outcome of TAO before administration of angiogenic factors.
[Show abstract][Hide abstract] ABSTRACT: Human T lymphotropic virus type I (HTLV-I) is a retrovirus which is associated with adult T cells leukaemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a minority of HTLV-I-infected individuals. It is not clear why a minority of HTLV-I-infected individuals develop HAM/TSP and majority remains lifelong carriers. It seems that the interaction between the virus and the immune response plays an important role in HTLV-I-associated diseases. Although the role of the immune response in HTLV-I pathogenesis is not fully understood, however it seems that the efficacy of the immune response which is involved in controlling or limiting of viral persistence determines the outcome of HTLV-I-associated diseases. Here we discuss the role of innate and adaptive immune response and also the risk factors contribute to the observed differences between HAM/TSP patients and asymptomatic HTLV-I carriers.
Preview · Article · Mar 2013 · Iranian Journal of Basic Medical Science
[Show abstract][Hide abstract] ABSTRACT: Objective(s): Since each unit of Intravenous Immunoglobulin (IVIG) is obtained from different blood donors, blood-borne viral diseases is of high importance. We aimed at investigating the prevalence of various viral infections: Human T-cell Lymphotropic Virus Type 1 (HTLV-I), Hepatitis B (HBV), Hepatitis C (HCV), and Human Immunodeficiency Virus (HIV) among patients referred for IVIG therapy section in Mashhad University of Medical Sciences, Mashhad, Iran.
Materials and Methods: A prospective study was conducted on 130 IVIG recipients admitted to different wards of our Medical Centre: Immunology, Hematology, and Neurology, in 2010. After filling the informed consent form, a 5 cc blood sample was initially taken from each patient. Viral infections including HTLV-I Ab, HIV-Ab, HBsAg, HBc-Ab, and HBV-Ab were assessed using the ELISA technique before and after six three months treatment.
Results: Test results for HTLV-I Ab, HBsAg, HBc Ab, HIV Ab, and HCV Ab were negative in all cases before IVIG therapy. After receiving IVIG, two female cases with CIDP showed positive results for HBV Ab (0.8%) and HBS Ag (0.8%) with ELISA and only one patient confirmed with PCR. There was not any significant relation between HBV Ag (P=0.14) and HBC Ab with type of disorder (P=0.66).
Conclusion: This study showed that HTLV-I viral replication and the other investigated viral transmissions do not occur in plasma; therefore, the IVIG products are safe.
Preview · Article · Mar 2013 · Iranian Journal of Basic Medical Science
[Show abstract][Hide abstract] ABSTRACT: Objective(s): The aim of this study was to investigate the association between HLA class I alleles (HLA-A*02, HLA-A*24, HLA-Cw*08, HLA-B5401) and proviral load in HTLV-I associated myelopathy/tropical spastic paraperesis (HAM/TSP) patients in Iranian population.
Materials and Methods: 20 new cases of HAM/TSP patients and 30 HTLV-I infected healthy carriers were recruited. Peripheral blood samples were collected. Peripheral blood mononuclear cells (PBMCs) were isolated. DNA was extracted from PBMC.HTLV-I proviral load was calculated by Taqman quantitative real time polymerase chain reaction (qRT-PCR). PCR sequence-speciﬁc primer (PCR-SSP) reactions were performed to detect HLA-A, HLA-B and, HLA-Cw alleles.
Results: There was no signiﬁcant difference in sex and age between asymptomatic and HAM/TSP group. The Mann-Whitney U test was used to compare proviral load between HAM/TSP patients and healthy carrier. Provirus load of HAM/TSP patients was signiﬁcantly higher than that of HCs (P=0.003, Mann–Whitney U test).Odd ratio was calculated to determine association between class I alleles including (HLA-A*02, HLA-A*24, HLA-Cw*08) and risk of HAM/TSP development. We couldn’t find any association between these class I alleles and risk of HAM/TSP development in our study. In our survey HLA-A*02, HLA-A24, HLA-Cw*08 didn’t have protective effect on proviral load (P=0.075, P=0.060 and 0.650 Mann–Whitney U test respectively).
Conclusion: In conclusion, certain HLA alleles with protective effect in one population may have not similar effect in other population. This may be because of pathogen polymorphism or host genetic heterogeneity and allele frequency in desired population.
Full-text · Article · Mar 2013 · Iranian Journal of Basic Medical Science
[Show abstract][Hide abstract] ABSTRACT: Chronic Idiopathic Urticaria is defined as recurrent hives occurring for at least 6 weeks. In the majority of cases, there is no identifiable underlying etiology despite extensive evaluation. A subset of these patients is classified as having autoimmune urticaria defined by the presence of a functional IgG antibody to the α subunit of the high-affinity IgE receptor (FceRIa) or to IgE. The aim of this study was to evaluate the effects of the drug atorvastatin in patients with chronic urticaria compared to the placebo.In this single-blind study, 50 patients suffering from chronic urticaria (15-45 years old) were selected and divided into two groups by simple randomization method. The first group was treated with atorvastatin and antihistamines and the second group (control group) was treated with placebo and antihistamines for 3 months. Urticaria severity was measured by score index, before and after the treatment course: ASST (Autologous serum skin test) was performed for all patients and sera were collected to measure cytokines. In cases, IL-5 decreased and IL-10 increased after treatment compared to the time point before treatment (p<0.05). All patients with severe utricaria according our scoring, had positive ASST.The patients with severe urticaria identified by urticaria score and ASST positivity had chronic idiopathic urticaria. By prescribing the Atorvastatin plus antihistamines in severe and resistant forms of urticaria, the use of more toxic medications like cytotoxic drugs may be avoided.
Full-text · Article · Sep 2012 · Iranian journal of allergy, asthma, and immunology
[Show abstract][Hide abstract] ABSTRACT: Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory myelopathy. The pathophysiology of HAM/TSP is not yet fully understood; therefore, effective therapy remains a challenging issue. This study was designed to evaluate the efficacy of interferon-alpha (IFN-α) in HAM/TSP patients in the Northeast of Iran. Forty-nine patients with a definite diagnosis of HAM/TSP were enrolled in this clinical trial. For six months, the patients received three million international units of subcutaneous IFN-α-2b per each injection. The dose regimen was daily injection for the first month, three times administration per week for the months 2 and 3, twice weekly injection for the months 4 and 5 and weekly injection for the sixth month. The clinical and laboratory responses were evaluated based on neurologic examinations and immunovirological markers. IFN-α had significant but temporary effect on the motor and urinary functions of the patients. Comparing to the baseline values, proviral load was significantly decreased one month after treatment in responders (495.20±306.87 to 262.69±219.24 p=0.02) and non-responders (624.86±261.90 to 428.28±259.88 p=0.03). Anti-HTLV-1 antibody titers were significantly decreased among responders (1152.1±200.5 to 511.6±98.2 p=0.009) and non-responders (1280.1±368.1 to 537.6±187 p=0.007). Flow cytometry showed no significant changes in CD4, CD8, CD4CD25 and CD16CD56 counts with IFN-α. The positive impact of IFN-α was observed during the treatment period with significant effects on some clinical aspects of HAM/TSP.
No preview · Article · Jun 2012 · Journal of neuroimmunology
[Show abstract][Hide abstract] ABSTRACT: Human T-lymphotropic virus type 1 (HTLV-I) is an important global health problem in the world mainly in the endemic areas of HTLV-I infection. It was previously reported that Mashhad, in northeastern Iran, is a new endemic region of HTLV-I. The aim of this study was to examine the prevalence and phylogenetic analysis of HTLV-I in Sabzevar, located in the southeast of Mashhad. In this cross-sectional study 1445 individuals were selected by multistage cluster sampling. Serum samples were screened for anti-HTLV-I antibody using enzyme-linked immunosorbent assay (ELISA); all of the ELISA-positive samples were confirmed by polymerase chain reaction (PCR). Long terminal repeat (LTR) sequencing was carried out to determine the type of HTLV-I in Sabzevar. In the primary screening by ELISA, 26/1445 (1.8%) of those sampled were reactive for HTLV-I antibody. Twenty-four out of 26 samples were confirmed HTLV-I infection by PCR (24/1445). The overall prevalence of HTLV-I infection in Sabzevar is 1.66%. The prevalence of the virus infection in men and women was 2.42% (11/455) and 1.31% (13/989), respectively. Seroprevalence was associated with age, increasing significantly among those older than 30 years (p=0.015), and a history of surgery (p=0.002), imprisonment (p=0.018), and hospitalization (p=0.005). Three out of 24 positive HTLV-I samples were selected for sequencing and phylogenetic analysis of LTR. The results showed that HTLV-I in Sabzevar belonged to the cosmopolitan subtype. The present study showed Sabzevar is a new endemic area for HTLV-I infection. Our study emphasizes that systemic HTLV-I screening of blood donors in Sabzevar and other cities in Khorasan province is important and should be taken into account.
No preview · Article · Jan 2012 · AIDS research and human retroviruses
[Show abstract][Hide abstract] ABSTRACT: Invariant natural killer cells (iNKT) are an important immunoregulatory T cell subset. Currently several flow cytometry-based approaches exist for the identification of iNKT cells, which rely on using the 6B11 monoclonal antibody or a combination of anti-Valpha24 and anti-Vbeta11 antibodies.
The aim of this study was to compare the ability of two flow cytometry-based methods for detecting the frequency of circulating iNKT cells.
The frequency of iNKT cells was detected in the peripheral blood of 37 healthy adult donors by flow cytometry using the 6B11 antibody or a combination of anti-Valpha24 and anti-Vbeta11 antibodies.
The frequency of iNKT cells detected by 6B11 antibody or by combination of anti-Valpha24 and anti-Vbeta11 antibodies was significantly different (0.54% vs. 0.31%, respectively, p<0.001) but the values were highly correlated (Spearman r = 0.742, p<0.0001).
The results of this study indicate that different combinations of mAbs detect different frequencies of peripheral blood iNKT cells and a consensus in the field needs to be established to allow better assessment of iNKT-related studies and suggest using different methods for accurate identification of iNKT cells.
Full-text · Article · Mar 2010 · Iranian journal of immunology: IJI
[Show abstract][Hide abstract] ABSTRACT: Invariant natural killer T cells (iNKT) are a small subset of T lymphocytes which are involved in a wide variety of immune responses. Human studies have reported a wide variation in the number of circulating iNKT cell among healthy donors as well as in some immunologic disorders while there is no or little data about the factors which affect the pool of circulating iNKT cells in human. Given the importance of iNKT cells in immunologic responses and variation in the number and phenotype of iNKT cells, the aim of this study was to evaluate the frequency of circulating iNKT cells in a cohort of healthy Iranian adults.
The number of circulating iNKT cells was measured among PBMC in a group of healthy Iranian adults by flow cytometry. iNKT cells were identified by using 6B11 monoclonal antibody or by coexpression of TCR Valpha24 and Vbeta11 chain.
The mean frequency of 6B11-iNKT cells and Valpha24-Vbeta11 iNKT cells among T lymphocytes, were 0.54% and 0.31%, respectively. Forty-five percent of 6B11-iNKT cells were CD4 positive, and there was a weak but significant inverse correlation between total 6B11-iNKT cells and their CD4-positive subset. There was no significant difference in the frequency of iNKT cells between males and females.
Results of this study show that the frequency of iNKT cells is fairly high among the Iranian population and suggest matching of study population for age, sex, and ethnic background in iNKT-related research. More studies are necessary to understand the factors that can affect the variation in the number of iNKT cells in healthy humans.
Full-text · Article · Jan 2009 · Cytometry Part B Clinical Cytometry
[Show abstract][Hide abstract] ABSTRACT: Background and Aims: Combined factor V and VIII deficiency (CF5F8D) is a rare hemorrhagic disorder. Treatment of patients with blood products has been associated with infections with blood-borne viruses. Due to absence of any survey on status of blood borne viruses in individuals with CF5F8D, we tried to address this question.Methods: Among 25 known cases, 24 individuals were assessed for hepatitis B and C viruses (HBV & HCV), human T lymphotropic virus type one (HTLV-I) and human immunodeficiency virus type1/2 (HIV1/2) using enzyme linked immunosorbent assay method.Results: In the group under survey, 2 cases (8.3%) were positive for anti-HCV. There was no infection with HBV, HTLV-I and HIV.Conclusions: Hepatitis C is a major health problem in CF5F8D, as in hemophiliacs, and may need more attention from manufacturers of blood products and more careful pre-transfusion screening of blood products for anti-HCV.
Full-text · Article · Jun 2008 · Hepatitis Monthly
[Show abstract][Hide abstract] ABSTRACT: Immune and inflammatory responses mediated by cytokines, play important roles in the pathophysiology of asthma. These responses are associated with overexpression of Th2 cytokines such as IL-4 and IL-13. These two cytokines use common receptors for signaling that lead to identical immunological effects and regulation of the Th1/Th2 balance. The aim of this study was to determine whether patients with allergic asthma display overexpression of IL-4 and IL-13 genes. Using RT-PCR, we examined the expression of IL-4 and IL-13 genes in twenty asthmatic cases and twenty normal individuals. Total levels of serum IgE and IL-4 were also determined by ELISA method. Expression of IL-13 gene in 70% of patients with allergic asthma was higher than controls (P=0.01). There was no correlation between the expression of IL-13 gene and total level of serum IgE (P=0.07). Expression of IL-4 gene was detected in 30% of the patients and none of the normal individuals as determined by RT-PCR (P=0.01). Mean of serum IgE levels in patients and controls were 84.9 IU/ml and 62.2 IU/ml, respectively. Level of serum IgE was more than 100 IU/ml in 30% of patients (P=0.03). Mean of serum IL-4 levels in patients and controls were 15.73 pg/ml and 13.07 pg/ml, respectively. There was a relation between levels of serum IgE and IL-4 in 73% of cases. The results showed that there was a correlation between the expression of IL-4 gene and the level of serum IL-4. Levels of serum IgE and IL-4 were considerably higher in asthmatics than non-asthmatic controls.
Full-text · Article · Jul 2007 · Iranian journal of allergy, asthma, and immunology