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behrouz nikbin

  • Ali Tootee, Behrouz Nikbin, Ensieh Nasli Esfahani, Babak Arjmand, Hamidreza Aghayan, Mostafa Qorbani, Aziz Ghahari, Bagher Larijani*
    Background

    In patients with diabetes, transplantation of stem cells increases C-peptide levels and induces insulin independence for some period. Today, this positive therapeutic outcome is widely attributed to the well-documented immunomodulatory properties of stem cells. The aim of this study was to report alternations (the trend of increase or decrease) in different lymphocyte populations in a stem cell clinical trial performed in our institute.  

    Methods

    Recorded data of a clinical trial conducted on 72 patients with type 1 diabetes who had received fetal stem cell transplantation several years ago and were regularly monitored before and after the procedure in 1, 3, 6, 12, 24 months were analyzed. In these regular follow-up visits, insulin demand, HbA1c, C-peptide, and alternation to B cell and T cell populations were analyzed and recorded. For the purpose of the current study, patients were retrospectively divided into 2 groups, namely, those with the positive response to treatment and patients without such response. Temporary positive therapeutic response was defined by 2 different indicators, namely, plasma C-peptide levels and insulin dose-adjusted A1C (IDAA1c), which was calculated as A1C (percent) + (4 × insulin dose (units per kilogram per 24 h). Data analysis was performed by means of SPSS Version 18.  

    Results

    Besides the short-term therapeutic effect, we observed remarkably significant alternations to the populations of B and T lymphocytes in the recipients. When patients were retrospectively assigned to 2 different groups of patients with a positive therapeutic response (based on C-peptide changes) and those without it, it was observed that alternations to different populations of B-cells and T-cells were significantly different in these 2 groups.  

    Conclusion

    Our results demonstrated that transplantation of stem cells leads to significant positive therapeutic outcomes in one group of patients who showed totally distinct patterns of alternation to different groups of lymphocytes.

    Keywords: Stem Cells, Type 1 Diabetes, Immune System, Lymphocytes
  • Kamal Abdolmohammadi, Tayebeh Mahmoudi, Shahrzad Nojehdehi, Lobat Tayebi, SeyedMahmoud Hashemi, Farshid Noorbakhsh, Alireza Abdollahi, Masoud Soleimani, Behrouz Nikbin, MohammadHossein Nicknam*
    Purpose

    Acute pancreatitis (AP) is an inflammatory disorder distinguished by tissue injury and inflammation of the pancreas. Using paracrine potential of mesenchymal stem cells (MSCs) provides a useful clinical approach in treating inflammatory diseases. We investigated the therapeutic effects of adipose-derived MSC conditioned medium (CM) and hypoxia preconditioned adipose-derived MSC conditioned medium (HCM) in cerulein-induced AP in mice.

    Methods

    AP was induced in C57BL/6 mice by intraperitoneal injection of cerulein (75 μg/ kg/h × 7 times). One hour following the last injection of cerulein, mice were treated with intraperitoneal injection of CM and HCM (500 µL/mice/30 min × 3 times). Twelve hours following the treatment, serum levels of amylase and lipase were measured. In addition, pancreas pathological changes, immunohistochemical examinations for evaluation of IL-6 expression and pancreatic myeloperoxidase (MPO) enzyme activity were analyzed.

    Results

    The in vitro results of the morphological, differentiation and immunophenotyping analyses confirmed that hypoxia preconditioned MSCs (HP-MSCs) conserve MSCs characteristics after preconditioning. However, HP-MSCs significantly expressed high mRNA level of hypoxia inducible factor 1-α and higher level of total protein. The in vivo findings of the current study showed that CM and HCM significantly reduced the amylase & lipase activity, the severity of pancreas tissue injury and the expression of IL-6 and MPO enzyme activity compared with the AP group. However, no significant difference between CM and HCM groups was demonstrated.

    Conclusion

    Use of CM and HCM can attenuate cerulein-induced AP and decrease inflammation in the pancreas tissue in AP mice.

    Keywords: Inflammation Acute pancreatitis, Cerulein, Mesenchymal stem cell, Conditioned medium, Preconditioning
  • Mahdi Aminikhah, Mir Saeed Yekaninejad, M.Hosein Nicknam, Farideh Khosravi, Mehrnaz Naroei Nejad, Bita Ansaripour, Batol Moradi, Behrouz Nikbin, Aliakbar Amirzargar *
    Background
    The high polymorphism in the human leukocyte antigen (HLA) genes can be used as an identity of individuals to compare with other populations. This extreme polymorphism in the HLA system is accountable for the differences in alleles and haplotypes among ethnic groups, populations, and the inhabitants of many regions.
    Objective
    To define the frequency of HLA alleles and haplotypes among the Sistanis, Sistani/Zaboli population in Iran.
    Methods
    In this study, genotyping of class I (A, B, C) and class II HLA (DRB1, DQA1, DQB1) loci were determined in 90 unrelated Iraninan Sistani people and the results were compared with 474,892 HLA chromosomes from a diverse worldwide population.
    Results
    The highest frequently observed alleles in this study were A*02:01, B*35:01, C*12:03, C*06:02, DRB1*11, DQA1*05:05, and DQB1*03:01. Furthermore, the most frequent 3-locus haplotypes were A*02:01-B*50:01*C*06:02, DRB1*11-DQB1*03:01-DQA1*05:05, and A*02:01-B*50:01-DRB1*07. The most occurring 4-locus haplotypes were A*02:01-B*50:01-C*06:02-DRB1*07 and A*02:01-B*50:01-DRB1*07-DQB1*02:01. A*02:01-B*50:01-C*06:02-DRB1*07-DQB1*02:01 and A*02:01-B*50:01-C*06:02-DRB1*07-DQB1*02:01-DQA1*02:01 were determined to be the predominant 5- and 6-locus haplotypes, respectively. The heat maps and multiple correspondence analyses based on the frequency of HLA alleles showed that Sistanis share a common genetic inheritance with other Iranian ethnic groups such as the people from Yazd and Fars except some differences with Baluchis, Iranian Jews, Lurs of Kohgiluyeh/Buyerahmad, and Arabs of Fars, which may arise from the admixture of these groups or with foreign subgroups over centuries, and also a close relatedness with some European populations.
    Conclusion
    These data could be useful for finding better donor matches for organ transplantation among Sistanis or other related Iranian ethnic groups, epidemiological studies of HLA-associated diseases, handling HLA genomics and mapping the migration pattern of different ethnic group.
    Keywords: Allele Frequency, Haplotype Frequency, Human Leukocyte Antigen, Population Relationship
  • Behrouz Nikbin, Mohammad Hossein Nicknam, Hossein Hadinedoushan, Bita Ansaripour, Batol Moradi, Mirsaeed Yekaninejad, Mahdi Aminikhah, Mohammad Mehdi Ranjbar, Ali Akbar Amirzargar
    The major histocompatibility complex (MHC) genes are the most polymorphic loci in the human genome and have been widely studied in various populations and ethnic groups. Investigations into the HLA genes and proteins have been useful tool for anthropological, transplantation and disease association studies. The polymorphism of the HLA class I (A, B, C) and class II (DRB1, DQA1, DQB1) genes were investigated in 90 unrelated Iranian individuals from Yazd province located in the center of Iran using sequence-specific primers (PCR-SSP). Allele and haplotype frequencies, expected/observed heterozygosity, unbiased expected heterozygosity, number of effective alleles, deviations from Hardy-Weinberg (HW) equilibrium and genetic diversity were computed. A total of 23, 48, 23, 24, 13 and 16 alleles for HLA-A, -B,-C, -DRB1, -DQA and -DQB loci were determined, respectively in the population study. The most frequent allele identified in this study were A*02:01 (18.889%), HLA-B* 51:01 (12.778%), HLA-C* 12:03 (17.033%), HLADRB* 11 (24.4%), HLA-DQA* 05:05 (20.55%) and HLA-DQB*03:01 (22.8%).Furthermore, the most frequent 3-locus haplotypes were DRB*11-DQA*05:01-DQB*03:01 (21.1%), HLAA*02:01- B *50:01- DRB*07:01 (4.9%) and A*26:01 –B* 38:01 –C*12:03(5%). The most 4-locus haplotype were A*11:01 –B* 52:01 –C*12:03 –DRB!*15(2.5%) and A*02:01 –B* 50:01 – DRB1*07:01 –DQB1*02:01(4.5%). The heterozygosity of the study population was confirmed the expected value and not deviated from Hardy-Weinberg equilibrium for all loci (p>0.05). Our study shows a close relatedness between Yazd population and other ethnic group of Iran despite some differences, which may be due to admixture of each one of these groups with each other or foreigner subpopulations during centuries. Moreover, the results of this study suggest that the Iranian population from Yazd province is in close vicinity with the Caucasians populations and far from the Korean and Japanese populations.
    Keywords: Human Leukocyte Antigen (HLA), Polymorphism, Class I, II, Yazd Province
  • Ensieh Nasli Esfahani, Ardeshir Ghavamzadeh, Nika Mojahedyazdi, Seyyedjafar Hashemian, Kamran Alimoghadam, Nar­Jes Aghel, Behrouz Nikbin, Bagher Larijani
    Background
    The aim of the present clinical trial was to investigate the efficacy of autologous bone marrow mesenchymal stem cells (BM-MSCs) in glycemic control of diabetic patients without using any immunosuppressive drugs over a nine-month period.
    Method
    Twenty-three patients with T1DM, at 5 to 30 years of age and in both sexes, participated in this study. This trial consisted of two phases; in the end of the first phase (three month after the transplantation), if the patient still needed exogenous insulin to control his/her glycemic state, the second phase of study was performed. In both phases, 100 milliliter of mixed mesenchymal stem cells and normal saline containing 2×10⁶ autologous cells/kg for each patient was delivered to patients through cubital vein. All patients were evaluated at 1, 3, 6 and 9 months after the procedure.
    Result
    Twenty-one patients underwent a second injection. Nine patients (39%) responded positively and 14 patients (61%) responded negatively based on their HbA1c levels and insulin requirements in both injections. Two patients became insulin-free during two rounds of injections. In responder patients, mean levels of C-peptide and HbA1c as well as prescribed insulin dosage significantly decreased compared to baseline measures (P=0.002, P=0.007 and P<0.001). In the second phase, responder patients did not show significant reduction in C-peptide levels compared to the baseline of the second phase. Mean levels of HbA1c and prescribed insulin dosage significantly decreased in comparison to the beginning of the study (P<0.05).
    Conclusion
    Transplantation of BM-MSC can be viewed as a promising, simple, safe, and efficient therapeutic modality for T1DM.
    Keywords: Hematopoietic stem cell transplantation, Diabetes mellitus type 1, Autologous
  • Ensieh Nasli Esfahani, Ardeshir Ghavamzadeh, Nika Mojahedyazdi, Seyyedjafar Hashemian, Kamran Alimoghadam, Nar­Jes Aghel, Behrouz Nikbin, Bagher Larijani
    Background
    The aim of the present clinical trial was to investigate the efficacy of autologous bone marrow mesenchymal stem cells (BM-MSCs) in glycemic control of diabetic patients without using any immunosuppressive drugs over a nine-month period.
    Method
    Twenty-three patients with T1DM, at 5 to 30 years of age and in both sexes, participated in this study. This trial consisted of two phases; in the end of the first phase (three month after the transplantation), if the patient still needed exogenous insulin to control his/her glycemic state, the second phase of study was performed. In both phases, 100 milliliter of mixed mesenchymal stem cells and normal saline containing 2×10⁶ autologous cells/kg for each patient was delivered to patients through cubital vein. All patients were evaluated at 1, 3, 6 and 9 months after the procedure.
    Result
    Twenty-one patients underwent a second injection. Nine patients (39%) responded positively and 14 patients (61%) responded negatively based on their HbA1c levels and insulin requirements in both injections. Two patients became insulin-free during two rounds of injections. In responder patients, mean levels of C-peptide and HbA1c as well as prescribed insulin dosage significantly decreased compared to baseline measures (P=0.002, P=0.007 and P<0.001). In the second phase, responder patients did not show significant reduction in C-peptide levels compared to the baseline of the second phase. Mean levels of HbA1c and prescribed insulin dosage significantly decreased in comparison to the beginning of the study (P<0.05).
    Conclusion
    Transplantation of BM-MSC can be viewed as a promising, simple, safe, and efficient therapeutic modality for T1DM.
    Keywords: Hematopoietic stem cell transplantation, Diabetes mellitus type 1, Autologous
  • Yadollah Shakiba, Susan Koopah, Ahmad Reza Jamshidi, Ali Akbar Amirzargar, Ahmad Massoud, Amir Kiani, Mohammad Hossein Nicknam, Bahareh Nazari, Behrouz Nikbin
    In this study we determined the frequency, sensitivity and specificity of anti cyclic citrullinated peptides (anti-CCP) IgG antibody, total rheumatoid factor (RF-T), and RF isotypes in Iranian patients with rheumatoid arthritis (RA) and their association with age, clinical and serological parameters.Anti-CCP and RF-T and RF isotypes level were measured in 418 patients and 399 healthy controls by enzyme-linked immunosurbant assay (ELISA). Additionally, serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), visual analog scale (VAS) and disease activity score (DAS28) were evaluated in RA patients.The anti-CCP was positive in 53.1% of RA patients and 4.7% of controls. The frequency of RF-T was 61.87% and 17.66% in RA patients and controls respectively. The prevalence of RF isotypes in RA patients was 46.52% for RF-IgM, 23.47% for RF-IgA and 21.74% for RF-IgG. 31.39% of RA patients were RF-IgM positive without RF-IgA and RF-IgG and 21.9% were positive for all three RF classes. The anti-CCP positive patients showed increased number of swollen joints. On the other hand, RF-T positive patients exhibited a longer disease duration, lower age of onset and also higher ESR, CRP level and increased swollen joints. RF-T titer was significantly higher in RA patients with active disease compared to remission, low and moderate active groups. The sensitivity and specificity were 53.1, 95.3 for anti-CCP antibody and 61.8, 82.3 for RF-T.Our results support that anti-CCP and RF titer maybe valuable in estimation of disease activity and other inflammatory parameters in RA patients.
    Keywords: Anti, CCP, C, Reactive Protein, Disease Activity, Rheumatoid Arthritis, Rheumatoid Factor
  • Mohammad Ali Sahraian, Mandana Mohyeddin Bonab, Sanaz Ahmadi Karvigh, Sepideh Yazdanbakhsh, Behrouz Nikbin, Jamshid Lotfi
    Background
    Mesenchymal stem cell therapy has been used in multiple sclerosis (MS) in order to modulate the course of the disease in previous studies. One of the major concerns in such cases is long term safety or efficacy of this type of therapy..
    Objectives
    This study was conducted to report the clinical status of five patients with secondary progressive multiple sclerosis and one patient with neuromyelitis optica, five years after an autologous intrathecal mesenchymal stem cell (MSC) injection..Patients and
    Methods
    The patients (three male, three female) had a progressive course nonresponsive to the conventional immunomodulatory treatments with Expanded Disability Status Scale (EDSS) score of 3.5 to 6. They received the MCSs after discontinuing other treatments. They were examined annually to assess the disease activity and possible complications..
    Results
    Two patients had no change in their EDSS scores. One was diagnosed to have Devic’s disease decreased one score in the EDSS, but experienced four relapses during these five years. Three patients had an increase in EDSS scores by 1-2 scores after five years. Two experienced relapses after injection. There was no significant adverse reaction, infection, or neoplasm during this period of follow up..
    Conclusions
    Intrathecal mesenchymal stem cell therapy for MS is generally safe and did not result in any adverse reaction like malignancy for a relatively long period of time. At least half of the patients had no change in their EDSS and the remaining patients had a delay in disease progress..
    Keywords: Multiple Sclerosis, Stem Cells, Mesenchymal Stem Cell Transplantation, Tissue Therapy
  • Banafsheh Nazari, Aliakbar Amirzargar, Behrouz Nikbin, Mohsen Nafar, Pedram Ahmadpour, Behzad Einollahi, Mahboob Lesan Pezeshki, Seyyed Mohammad Reza Khatami, Bita Ansaripour, Hassan Nikuinejad
    There are limited clinical investigations identifying the percentage of T helper 1 (Th1) and T regulatory (Treg) cells in stable as well as rejected kidney allografts, a concept which needs to be more studied. The aim of our study was to compare the percentage of CD4+ IFN-γ+ cells, the number of IFN-γ secreting cells and the amount of FoxP3 expression in patients with or without stable graft function, to determine the roles of these immunological factors in stable and rejected renal allografts.In this prospective study, 3 months after transplantation 30 patients who received renal transplants from unrelated living donors were enrolled and divided into two groups, 20 patients with stable graft function and 10 patients with biopsy proven acute rejection.The percentage of Th1 CD4+ IFN-γ+ cells was determined on PBMC by flow cytometry and the number of IFN-γ secreting cells by ELISPOT method. Furthermore, FoxP3 expression of PBMCs was measured by Real Time PCR method. The results of these assessments in both groups were statistically analyzed by SPSS 14.0. Our results showed that the percentage of Th1 CD4+ IFN-γ+ cells and the number of IFN-γ secreting cells were significantly higher in the patients with acute rejection in comparison to the stable graft function group (p<0.001). In addition, the level of FoxP3 gene expression was higher in the group with stable graft compared to the acute rejection group.The higher percentage of CD4+ IFN-γ+Th1 subset and number of IFN-γ secreting cells and also the lower expression of Foxp3 could prone the patients to acute rejection episode post transplantation. By these preliminary data, it is suggested that monitoring of Th1 cells post transplantation, as an immunologic marker could perdict the possibility of rejection episodes.
    Keywords: Graft Rejection, Interferon, gamma, Kidney Transplantation, Th1 Cells
  • Bagher Larijani, Ensieh Nasli Esfahani, Peyvand Amini, Behrouz Nikbin, Kamran Alimoghaddam, Somayeh Amiri, Reza Malekzadeh, Nika Mojahed Yazdi, Maryam Ghodsi, Yahya Dowlati, Mohammad Ali Sahraian, Ardeshir Ghavamzadeh
    Stem cells are undifferentiated cells with the ability of proliferation, regeneration, conversion to differentiated cells and producing various tissues. Stem cells are divided into two categories of embryonic and adult. In another categorization stem cells are divided to Totipotent, Multipotent and Unipotent cells.So far usage of stem cells in treatment of various blood diseases has been studied (such as lymphoblastic leukemia, myeloid leukemia, thalassemia, multiple myeloma and cycle cell anemia). In this paper the goal is evaluation of cell therapy in treatment of Parkinson''s disease, Amyotrophic lateral sclerosis, Alzheimer, Stroke, Spinal Cord Injury, Multiple Sclerosis, Radiation Induced Intestinal Injury, Inflammatory Bowel Disease, Liver Disease, Duchenne Muscular Dystrophy, Diabetes, Heart Disease, Bone Disease, Renal Disease, Chronic Wounds, Graft-Versus-Host Disease, Sepsis and Respiratory diseases. It should be mentioned that some disease that are the target of cell therapy are discussed in this article.
  • Farinaz J. Ghods, Ghasem Solgi, Ali Akbar Amirzargar, Behrouz Nikbin, Ahad J. Ghods
    Introduction. Mannose-binding lectin (MBL) constitutes defense against infections when adaptive immune response is compromised. Elevation in serum MBL levels has been shown in patients with kidney failure. We compared serum MBL levels before and after kidney transplant and evaluated association of MBL deficiency with infectious complications in kidney transplant recipients. Materials and Methods. This study was performed in 71 kidney transplant recipients and 48 healthy controls. In 36 recipients (group 1), serum MBL levels were tested before and on days 7 and 14 after transplantation. They were followed up for 6 months. In 35 recipients (group 2), serum MBL was measured during their posttransplant follow-up visits. In both groups, frequencies of clinically significant infections and acute rejection were compared between those with low MBL (< 500 ng/mL) and normal/high MBL (≥ 500 ng/mL). Results. Serum MBL levels (1744 ± 905 ng/mL) were not higher in group 1 before transplantation than in controls. One and 2 weeks after transplantation, MBL levels decreased to 1699 ± 1030 ng/mL and 1562 ± 1020 ng/mL, respectively. Five patients who had low serum MBL levels experienced more frequent episodes of infections (P =. 008) and CMV disease (P <. 001). Ten patients in group 2 with low MBL levels had more frequent episodes of CMV disease (P =. 01). Conclusions. These findings suggest a potential role for MBL in defense against developing posttransplant CMV disease and that low serum MBL levels in kidney transplant recipients be considered an indicator of the need for CMV prophylaxis.
  • Masoud Movahedi, Mostafa Moin, Mohammad Gharagozlou, Asghar Aghamohammadi, Saied Dianat, Batoul Moradi, Mohammad Hossein Nicknam, Behrouz Nikbin, Aliakbar Amirzargar
    Asthma is a complex and multifactorial disorder. Several studies have reported association between different HLA- DQB1 and HLA- DRB1 alleles and allergic asthma. The aim of the present study was to investigate the association of HLA-class II alleles and haplotypes, with total serum IgE and the results of the skin prick test in Iranian children with allergic asthma. A total of 112 patients with allergic asthma symptoms (75 males and 37 females) were selected randomly from the pediatric hospital. In some patients total serum IgE and prick test were determined. Data of this study shows that HLA-DRB1*12 significantly increased in asthmatic patients (4.5% vs. 0%, P-value=0.04). HLA-DQB1*0603 and 0604 alleles were significantly higher in asthmatics than those in normal controls (10% vs. 0%, P-value= 0.0001; and 9.3% vs. 3.7%, P-value= 0.04, respectively). The statistical significance was relinquished after p value correction for all alleles except for HLA-DQB1*0602 (Pc=0.03) and HLA-DQB1*0603 (Pc=0.0015). Conversely, HLA-DQB1*0501 and 0602 were decreased in asthmatics compared to normal controls (7.5% vs. 13.5%, P-value= 0.05; and 4% vs. 12.5%, P-value= 0.002, respectively). The mean of total IgE in patients was 483 IU, and it was significantly high about 1140 IU in asthmatic patients with positive skin prick test to house dust. The most frequent alleles in asthmatic patients with the total IgE>200 IU/mL were HLA-DRB1*11and 1401, HLA-DQA1*0505, HLA-DQB1*0301 and in patients with total IgE<200 IU/mL were HLA-DRB1*0301, 07 and 1301, HLADQA1*0201 and 0301, HLA-DQB1*0201.These data suggests that HLA-DRB1, DQA1 & DQB1 alleles and haplotypes might be implicated in susceptibility to allergy and asthma and serum IgE production. As asthma and atopy are multifactorial disorders, probably HLA genes are involved in the regulation of immune specific responses to common allergen.
  • Hossein Mortazavi, Ali Akbar Amirzargar, Mahin Valikhani, Zahra Hallaji, Maryam Daneshpazhouh, Mohammad Javad Nazemi Tabrizi, Hassan Seirafi, Behrouz Nikbin, Farideh Khosravi, Siyavash Toosi, Cheida Chams, Davatchi
    Background
    In addition to humoral immunity associated with anti-desmoglein antibodies, cellular immunity and mediators including cytokines are involved in the pathogenesis of pemphigus vulgaris. In this study we evaluated the level of IL-2, IFN-γ, TNF-α, IL-4, and IL-10 in the sera of patients with pemphigus vulgaris before and after treatment.
    Methods
    A total number of 71 new patients with pemphigus vulgaris were included in the study. The above mentioned cytokines were measured in patients with a mild disease (20 bullae or less) and a severe disease (60 bullae or more) using ELISA method before and 4 weeks after treatment with 2 mg/kg/day prednisolone and 2mg/kg/day azathioprine. We also measured IL-4 and IL-10 in 69 mildly and 70 severely affected patients only at the beginning of the study. All patients had muco-cutaneous phenotype. Patients with a mild disease had mild mucosal involvement and patients with a severe disease had moderate to severe mucosal involvement. Serum levels of IL-2 and IFN-γ were also measured in 27 normal controls.
    Results
    In the total study population, the level of IL-2 decreased from 103.9 pg/ml to 82.79 pg/ml after treatment (p=0.05). Comparing cytokines between 2 groups (severe and mild), the level of IL-2 before treatment showed significantly lower figures in severe patients (147.27 versus 67.38, p=0.04). On the other hand, IFN-γ after treatment was significantly higher in severe patients (0.75 versus 0.42, p=0.04).
    Conclusion
    Mean level of IL-2 is lower in severe pemphigus vulgaris patients than that of mild disease. This finding indicates that, in pemphigus vulgaris, IL-2 level negatively correlates with the severity of the disease and widespread underlying autoimmune process. The data also suggests that the level of IFN-γ directly correlates with the severity of the disease.
  • Hossein Ali Khazaei, Nima Rezaei, Asghar Aghamohammadi, Ali Akbar Amirzargar, Khadidjeh Mollaei Ghasemi, Ibrahim Mirimoghaddam, Behrouz Nikbin
    Abstract: This study was performed to determine the genetic diversity of HLA class I and II alleles among two ethnic groups in Southeastern Iran. HLA profiles were determined in 71 Iranian populations (41 Zaboli and 30 Baloch). The frequencies of HLA-A02 (p=0.017), -Cw4 (p=0.003), and -DR8 (p=0.025) in the Zaboli populations were significantly higher than that in Baloch ethnic group. In contrast, the frequency of HLA-A23 allele was more frequent in Baloch than Zaboli (p=0.020). This report represents an important resource for investigators in the fields of transplantation immunology and population genetics from widely dispersed areas of Iran.
  • Farideh Khosravi, Aliakbar Amirzargar, Abdolfatah Sarafnejad, Mohammad Hossein Nicknam, Kamran Alimoghadam, Saied Dianat, Ghasem Solgi, Behrouz Nikbin
    Previous studies demonstrated significant differences in a number of HLA allele frequencies in leukemia patients and normal subjects. In this study, we have analyzed HLA class II alleles and haplotypes in 110 leukemia patients (60 acute myelogenous leukemia “AML”, 50 chronic myelogenous leukemia”CML”) and 180 unrelated normal subjects. Blood samples were collected from all of the patients and control subjects. DNA was extracted by salting out method and HLA typing was performed using PCR-SSP method. Significant positive association with AML was obtained for HLA-DRB1*11allele (35% vs. 24.7%, P=0.033). Two alleles including HLA-DRB4 and –DQB1*0303 were significantly less frequent in AML patients than in controls. HLA-DQB1*0303 allele was never observed in CML patients compared with allele frequency in controls (4.2%). According to haplotype analysis, HLA-DRB1*0101/DQA1*0104/-DQB1*0501 frequencies were significantly higher and –DRB1*16/-DQA1*01021/-DQB1*0501 frequencies were significantly lower in CML patients than in controls. In conclusion it is suggested that HLA-DRB1*16 allele and HLA-DRB1*15/-DQA1*0103/-DQB1*06011 and –DRB1*16/-DQA1*01021/-DQB1*0501 haplotypes predispose individuals to AML and HLA-DRB4 allele predispose to CML. Future studies are needed to confirm these results and establish the role of these associations in AML and CML.
  • Mandana Mohyeddin Bonab, Sepideh Yazdanbakhsh, Jamshid Lotfi, Kamran Alimoghaddom, Fatemeh Talebian, Farnaz Hooshmand, Ardeshir Ghavamzadeh, Behrouz Nikbin
    Background
    Mesenchymal stem cells (MSCs) with their potential to differentiate into mesodermal and non-mesodermal lineages have several immunomodulatory characteris-tics. These properties make them promising tools in cell and gene therapy.
    Objective
    To evaluate the potential therapeutic applications of autologous MSC in improving clinical manifestations of MS patients.
    Methods
    Ten patients were included in this pi-lot study. All had progressive disease that had not responded to disease modifying agents including Mitoxantrone. Their Expanded Disability Status Scale (EDSS) score ranged from 3.5 to 6. Patients were injected intrathecally with culture expanded MSCs. They were followed with monthly neurological assessment and a MRI scan at the end of the first year.
    Results
    During 13 to 26 months of follow up (mean: 19 months), the EDSS of one patient improved from 5 to 2.5 score. Four patients showed no change in EDSS. Five patients’ EDSS increased from 0.5 to 2.5. In the functional system assess-ment, six patients showed some degree of improvement in their sensory, pyramidal, and cerebellar functions. One showed no difference in clinical assessment and three deterio-rated. The result of MRI assessment after 12 months was as following: seven patients with no difference, two showed an extra plaque, and one patient showed decrease in the number of plaques.
    Conclusion
    This preliminary report emphasizes on the feasibility of autologous MSC for treatment of MS patients. However, in order to draw a definitive conclusion a larger sample size is required.
  • مریم کشاورز، فریده خسروی، بهروز نیک بین، ملکتاج هنرمند، عبدالفتاح صراف نژاد
    هدف
    نفروز یا نفروز لیپوئیدیک باعث هشتاد درصد از موارد نشانگان نفروتیک کودکان می باشد که با عوارض کلیوی تشخیص داده می شود. پروتئینوری از عوارض اصلی آسیب به سد گلومرولی کلیه است و نقش IgE در ایجاد آسیب های گلومرولی ممکن به نظر می رسد. در این تحقیق میزان IgE سرمی کودکان مبتلا به نفروز هنگام حمله یا عود بیماری، هنگام درمان استروئیدی و بعد از درمان استروئیدی تعیین شد تا نقش احتمالی IgE در بروز نفروز بررسی گردد.
    مواد و روش ها
    مطالعه بر روی کودکان حساس به درمان استروئیدی انجام گرفت و برای اندازه گیری میزان IgE، از روش الایزای ساندویچی با دقت 5Iu/ml استفاده گردید.
    نتایج
    میانگین IgE سرم مبتلایان هنگام حمله یا عود بیماری 8/274Iu/ml با انحراف معیار 6/14 می باشد. هنگام درمان استروئیدی میانگین IgE سرم 59/176Iu/ml با انحراف معیار 82/14 می باشد و بعد از قطع درمان استروئیدی میانگین IgE سرم 9/234Iu/ml با انحراف معیار 58/14 در نظر گرفته شد.
    نتیجه گیری
    کاهش میزان IgE در هنگام درمان استروئیدی مشاهده شد که معنی دار نمی باشد. با وجود این مواردی از کاهش شدید IgE ازهنگام حمله بیماری تا قطع درمان استروئیدی دیده شد. بنابراین، به نظر می رسد عوامل حساسیت زا در برخی افراد باعث حمله یا عود بیماری می شود؛ در مجموع نقش IgE در ایجاد نفروز، کم اهمیت است.
    کلید واژگان: نفروز، نشانگان نفروتیک با تغیرات جزیی، IgE، پردنیزولون
    Maryam Keshavarz, Farideh Khosravy, Behrouz Nikbin, Malektaj Honarmand, Abdolfatah Sarafnejad
    Objectives
    The idiopathic minimal change nephritic syndrome (nephrosis) is responsible in 80% of nephritic syndromes in children. It is a clinical entity characterized by inter and outer renal parameters. Main factor in glomerolar damages is proteinuria and the role of IgE is possible.
    Aim
    In this research, serum IgE concentrations were measured in children with nephrosis in three stages: Relapse, Remission in treatment with steroids, Remissions after treatment with steroids.
    Materials And Methods
    Study was done on children under 16 years old that suffered from nephrosis. They treated with Prednisolone. Serum IgE concentrations were measured by ELISA technique.
    Results
    Average Concentration of serum IgE in the relapse phase was 274.8 Iu/ml (SD=14.6); It was in the remission with steroids treatments 179.59 Iu/ml (SD= 14.82) and it was 234. 9 Iu/ml (SD=14.58) in the remission phase after treatment with steroids.
    Conclusion
    In some cases IgE is significantly reduced after steroid treatment therefore it seems possible that allergic agents can trigger or increase the disease. Serum IgE concentration was not a main factor in nephritic syndrome.
  • Behrouz Nikbin, Mandana Mohyeddin Bonab, Fatemeh Talebian
    Tissue and cell transplantation are regarded as a popular procedure in clinical sciences, prospecting a new horizon for several incurable diseases. Along with its usefulness, many ethical concerns accompany this development. The ethical issue of organ transplant is unique to the source used which includes: living related, living unrelated, cadaveric, and xenotransplant. Obtaining organs has a separate set of ethical concerns which are discussed under two headings, namely salvage and donation. Then there is the issue of organ marketing and the ethical, social, and economical issues it encompasses. All these are active areas of debate, and we have touched upon them by turn. This century has brought a new aspect of transplantation into the light, stem cell transplantation. Here we present some work done recently on mesenchymal stem cells and their outcome. These cells are now being employed in the therapy of some incurable ailments. It seems this kind of transplantation, although possessing its own range of issues, could prove to be the way of the future.
  • Mahboob Lessan, Pezeshki, Ali Akbar Amirzargar, Nooshin Golabi, Mohammadreza Khatami, Behzad Einollahi, Vahid Pourfarziani, Farideh Khosravi, Hassaneh Tajerzadeh, Behrouz Nikbin
    Methods
    16 non-diabetic kidney transplant candidates (4 females and 12 males، age = 20-65 yr، first time transplant) were selected. The transplanted patients were divided into two groups based on the rejection during 3 weeks post transplant: group I (n = 9) without rejection and group II (n = 7) with a rejection episode. Immune parameters including lymphocytes subpopulations (by flowcytometry) and immunoglobulin classes (IgM، IgG، IgA and IgE by nephlometric assay) before and 45 days after transplantation were determined.
    Results
    The results of this investigation showed that the level of immunoglobulin IgG، IgM، IgA and IgE decreased post transplantation due to immunosuppressive drugs. CD3، CD4، CD8 T cells count، CD56 NK cells count and CD20 B cells count pre- and post-transplantation did not show any significant differences. The amount of IgE (220 vs. 462 IU/ml)، CD3 (62% vs. 69. 7%) and CD4 (35% vs. 41. 3%) cells increased in group II during rejection episode pre-transplantation. In addition، IgA increased pretransplantation in group I those without rejection episode in comparison with group II with a rejection episode. Forty five days post transplantation IgA (209 vs. 152 mg/dl)، IgG (1009 vs. 703 mg/dl) and CD20 (15% vs. 10%) increased in group I patients.
    Conclusion
    It is suggestive that pre-transplantation increases IgE، CD3 and CD4 are predictive of acute rejection.
  • Mortaza Bagheri_Ali Akbar Amirzargar_Ardeshir Ghavamzadeh_Kamran Alimoghadam_Farideh Khosravi_Bita Ansaripour_Batoul Moradi . Behrouz Nikbin
    Background
    -thalassemia as a hereditary disease is defined as defective synthesis of -globin chains, resulting in erythropoiesis abnormalities and severe anemia. Different studies have shown that cytokines and cytokine gene polymorphisms play a major role in the pathogenesis of -thalassemia. Single nucleotide polymorphisms (SNPs) within the promoter region or other regulatory sequences of cytokine genes lead to overall production of cytokines.
    Objective
    To analyze the genetic profile of Th1 and Th2 cytokines in Iranian patients with -thalassemia major.
    Methods
    Allelic and genotype frequencies of cytokine genes were determined in 30 thalassemia patients and 40 healthy subjects using PCR-SSP assay. Allele and genotype frequencies were calculated and compared with those of normal controls.
    Results
    The results of our study show a significant decrease in A allele at position UTR 5644 IFN-, G alleles at position -238 TNF- and 166 IL-2, and C allele at position -590 IL-4. TGFhaplotype TG/TG increased whereas TGF- haplotype CG/CG and IL-10 haplotype GCC/ACC decreased significantly in all patients.
    Conclusion
    Data of this investigation suggest that variations among cytokine gene polymorphisms may contribute to the disease susceptibility. A finding which needs to be fairly clarified in other ethnic groups.
  • Behrouz Nikbin, Nader Tajik, Ali Saraji, Gholam Reza Pourmand, Fatemeh Talebian, Abdursuk Mehrsai
  • Ali Akbar Amirzargar, Abdol Ali Danesh, Farideh Khosravi, Mohammad Hossein Niknam, Behrouz Nikbin
    Background
    Pulmonary tuberculosis (PTB) has recently become a major problem indeveloped countries especially in immune compromised HIVinfected individuals. Cytokines, their genes and receptors have been implicated in the protective immunity, pathophysiology and development of tuberculosis.
    Material and Methods
    In the present study the genotype frequencies of a number of polymorphic genes coding for cytokines or for cytokine receptors have been investigated in a case control study including a group of 40 Iranian PTB patients and 40 healthy individuals. The allelic polymorphism of cytokines SNPs were analyzed according to the protocols of the cytokine component designed for the 13th IHW by the Heidelberg University group. Using PCR-SSP method the following cytokine genes have been determined: IL-1 (T/C –889), IL-1 (C/T +3962), IL-1R (C/T pstI 1970), IL-1RA(T/C mspaI 1100), IL-4RA(G/A+1902), IL- 12 (C/A –1188), TGF- (C/T codon 10, G/Ccodon 25), TNF- (G/A –308, G/A –238), IL-2 (T/G –330 G/T +166), IL-4 (T/G –1098, T/C –590, T/C –33), IL-6 (G/C –174, G/A nt 560), IL-10 (G/A –1082, C/T –819, C/A –592).
    Results
    From IL-1R cluster (pro- inflammatory cytokines) a positive significant association was found at position pstI 1970 C/T polymorphismwhere theC allele was over presented in the PTBpatients (60% vs. 37.5%, P = 0.04).Asignificant negative association at codon 10 TGF- C/T polymorphism has also been shown in our patients, where the T allele was not detected in the patients but 10% of the control subjects expressed this allele (Fisher exact test, P = 0.05). At this codon allele T (Leucine substitution) is associated with high TGFproduction. For TNF an insignificant tendency was found at position -308 A/G polymorphismwhere theG allele carried by 80% of cases and 65% of controls (P = 0.07).At position -238 a negative association was found at the GApolymorphism(10% vs. 25%, P = 0.07). For IL-6 an insignificant positive association at position -174 C/G *Corresponding author: Dr. Ali Akbar Amirzargar, Department of Immunology, Immunogentic Laboratory, Medical School, Tehran University of Medical Sciences. e-mail: Amirzargar_Ali@yahoo.com Cytokine gene polymorphismin Pulmonary TBpolymorphism, G allele (57.5% vs. 37.5, P = 0.07) was found. At the other cytokine genes no specific association were found.
    Conclusion
    In conclusion it is suggested that C allele at position pstI 1970 of IL-1 cluster increases and T allele at codon 10 of TGF- decreases in PTB patients.
  • Mohammad Hossein Nicknam, Ali Torkashvand, Ahmad Ghods, Ali Akbar Amirzargar, Aref Amirkhani, Farideh Khosravi, Behrouz Nikbin
    Studies have shown that patients who do not produce donor specific and / or panel reactive anti-HLA antibodies have a longer graft survival. The purpose of this study was to evaluate the posttransplant humoral immune response towards HLA-class I antigens and the measurement of the serum creatinine levels which are used in monitoring posttransplant function of kidney. Serum samples from 132 renal transplant recipients were screened for preformed anti-HLA class I panel reactive antibodies (PRA) by means of microlymphocytotoxicity assay. The results revealed the presence of PRA in 26 (19.7%) out of 132 transplanted patients. Graft function was evaluated by measurement of serum creatinine levels which revealed the mean of 1.75 mg/dl (SD: 1.08). Because of clinical significance of presence of different PRA amounts (>10%, > 20% and >50% of panel reactivity) in patients, correlation with kidney function status was analyzed. The obtained data highlighted a higher presence of serum creatinine levels in PRA-positive patients compared to negative patients (P<0.01). These results (and further studies for class II, …) can be used to implement new therapeutic strategies to curtail post transplant alloantibodies production and better
  • Ali Akbar Amirzargar, Morteza Bagheri, Ardeshir Ghavamzadeh, Kamran Alimoghadam, Farideh Khosravi, Mohammad Hossein Niknam, Mandana Moheydin, Bita Ansaripour, Batul Moradi, Behrouz Nikbin
  • Hossein Ali Khazaei, Asghar Aghamohammadi, Nima Rezaei, Behrouz Nikbin, Aliakbar Amirzargar, Farideh Khosravi, Mohammad Ali Khosravi, Ibrahim Mirimoghaddam
    The human leukocyte antigen has become a key component in investigating the genetic relationships between populations. The aim of this study was to determine the genetic diversity of HLA class I and II alleles among Zaboli ethnic group of South-east Iran to establish a database for further investigations on ancestry and the genetic factors contributing to complex diseases in this region.Unrelated individuals from the Southeast geographic location throughout Iran were serologically typed using standard microcytotoxicity assays with commercial and local trays. The ethnic background of each individual was self-defined. HLA profiles were determined in 41 Zaboli populations. The most frequent class I alleles of the Zaboli ethnic group being the following: HLA-A1 (34.1%), -A2 (58.5%), -A11 (29.3%), -A24 (23.9%), -B5 (70.7%), -B16 (26.8%), and -Cw4 (24.4%). The class II alleles more frequently observed in this group were HLA-DR1 (26.8%), -DR2 (26.8%), -DR3 (31.7%), -DR4 (29.3%), -DR7 (24.4%), -DR8 (22%), -DR11 (48.8%), -DRw52 (73.2%), -DRw53 (53.7%), -DQ1 (53.7%), -DQ2 (31.7%), and -DQ3 (29.3%). This report utilized a first study of HLA class I and II typed individuals, from widely dispersed areas of Iran. This will help in studies related to disease associations and cadaver organ allocation programmes.
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