Farhad Shahsavar; Nader Tajik; Kobra-Zinat Entezami; Masoomeh Fallah Radjabzadeh; Behnam Asadifar; Kamran Alimoghaddam; Mohammadreza Ostadali Dahaghi; Arash Jalali; Andisheh Ghashghaie; Ardeshir Ghavamzadeh
Volume 7, Issue 1 , March 2010, , Pages 8-17
Abstract
Background: Interaction between killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I molecules is important for regulation of natural killer (NK) cell function. Objective: The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility ...
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Background: Interaction between killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I molecules is important for regulation of natural killer (NK) cell function. Objective: The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility to acute leukemia. Methods: Cohorts of Iranian patients with acute myeloid leukemia (AML; n=40) and acute lymphoid leukemia (ALL; n=38) were genotyped for seventeen KIR genes and their three major HLA class I ligand groups (C1, C2, Bw4) by a combined polymerase chain reaction–sequence-specific primers (PCR-SSP) assay. The results were compared with those of 200 healthy control individuals. Results: We found a significantly decreased frequency of KIR2DS3 in AML patients compared to control group (12.5% vs. 38%, odds ratio=0.23, p=0.0018). Also, the KIR3DS1 was less common in AML group than controls (27.5% vs. 44.5%, p=0.0465, not significant after correction). Other analyses including KIR genotypes, distribution and balance of inhibitory and activating KIR+HLA combinations, and co-inheritance of activating KIR genes with inhibitory KIR+HLA pairs were not significantly different between leukemia patients and the control group. However, in AML patients a trend toward less activating and more inhibitory KIR-HLA state was observed. Interestingly, this situation was not found in ALL patients and inhibition enhancement through increase of HLA ligands and inhibi-tory combinations was the main feature in this group. Conclusion: Our findings may suggest a mechanism for escape of leukemic cells from NK cell immunity.
Mandana Mohyeddin Bonab; Sepideh Yazdanbakhsh; Jamshid Lotfi; Kamran Alimoghaddom; Fatemeh Talebian; Farnaz Hooshmand; Ardeshir Ghavamzadeh; Behrouz Nikbin
Volume 4, Issue 1 , March 2007, , Pages 50-57
Abstract
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 ...
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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.
Andisheh Ghashghaie Mansour; Seyyed Hamidollah Ghaffari; Kamran Ali-moghadam; Ardeshir Ghavamzadeh
Volume 3, Issue 2 , June 2006, , Pages 95-98
Abstract
Background: HLA compatibility between transplant donor and recipient is one of the major determinants of transplant outcome. Objective: To determine HLA class I by PCR- Sequence-Specific Oligonucleotide Probe (PCR-SSOP) in cord blood donors. Methods: Genomic DNA of 142 cord blood samples registered ...
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Background: HLA compatibility between transplant donor and recipient is one of the major determinants of transplant outcome. Objective: To determine HLA class I by PCR- Sequence-Specific Oligonucleotide Probe (PCR-SSOP) in cord blood donors. Methods: Genomic DNA of 142 cord blood samples registered at the Cord Blood Bank of Iran at Hematology, Oncology, and Bone Marrow Transplantation Research Center, was prepared and HLA class I was determined by the PCR-SSOP. Results: A total of 284 HLA-A alleles was identified of which A*02 and A*24 were the most common. Among 284 HLA-B and HLA-C alleles, B*35, B*51, Cw*4 and Cw*12 were the most frequent alleles in the studied population. Conclusion: Amplification of HLA loci with PCR-SSOP has proved to be a reliable method for HLA-A, -B and -C genotyping.
Nahid Naderi; Ali Akbar Pourfathoolah; Mahin Nikougoftar; Kamran Alimoghadam; Ardeshir Ghavamzadeh; Seyed Mohammad Moazzeni
Volume 2, Issue 1 , March 2005, , Pages 21-28
Abstract
Background: Dendritic cells (DCs) are the most potent stimulators of primary T cell responses and play a key role in immune reactions after stem cell transplantation. Very little is known about the cord blood (CB) dendritic cells and their potential involvement in the low incidence and lower severity ...
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Background: Dendritic cells (DCs) are the most potent stimulators of primary T cell responses and play a key role in immune reactions after stem cell transplantation. Very little is known about the cord blood (CB) dendritic cells and their potential involvement in the low incidence and lower severity of acute graft-versus-host disease after CB transplantation. Objectives: The aim of this study was the isolation of cord blood and peripheral blood dendritic cells and comparison of their functional competence and determination of their probable role in graft versus host disease after stem cell transplantation. Methods: In this study, fresh peripheral blood DCs (PBDCs) were enriched as HLA-DR + cells, lacking the CD3, CD11b, CD14, CD16, CD19 and CD56, using immunomagnetic bead depletion. For cord blood dendritic cells (CBDCs) enrichment CD34 + and CD66b+ cells were needed to be depleted too. Immunomagnetically enriched PB/CB dendritic cells were co-cultured with adult T lymphocytes and cell proliferation was measured by 3H-thymidine incorporation. Results: Results showed that CBDCs were significantly poor stimulators of the mixed leukocyte reaction as compared with PBDCs (P < 0.05). Conclusion: The demonstrated impairment of CBDCs function could be of importance in interpretation of the low incidence and milder severity of graft-versus-host disease (GVHD) in umbilical CB transplantation compared with peripheral blood or bone marrow stem cell transplantation.
Morteza Bagheri; Ali Akbar Amirzargar; Ardeshir Ghavamzadeh; Kamran Alimoghadam; Farideh Khosravi; Bita Ansaripour; Batoul Moradi; Behrouz Nikbin
Volume 2, Issue 1 , March 2005, , Pages 43-49
Abstract
Background: β-thalassemia as a hereditary disease is defined as defective synthesis of β-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 ...
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Background: β-thalassemia as a hereditary disease is defined as defective synthesis of β-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 β-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 β-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- γ, G alleles at position -238 TNF- α and 166 IL-2, and C allele at position -590 IL-4. TGF- β haplotype TG/TG increased whereas TGF-β 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.
Ali Akbar Amirzargar; Morteza Bagheri; Ardeshir Ghavamzadeh; Kamran Alimoghadam; Farideh Khosravi; Mohammad Hossein Nicknam; Mandana Moheydin; Bita Ansaripour; Batul Moradi; Behrouz Nikbin
Volume 1, Issue 1 , June 2004, , Pages 26-33
Abstract
Background:It has been hypothesized that genetic factors other than histocompatibility disparity may play a role in predisposition to developing Chronic Myelogenous Leukemia (CML). In this regard, Th1 and Th2 cytokines and their gene polymorphism seems to be important. Overall expression and secretion ...
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Background:It has been hypothesized that genetic factors other than histocompatibility disparity may play a role in predisposition to developing Chronic Myelogenous Leukemia (CML). In this regard, Th1 and Th2 cytokines and their gene polymorphism seems to be important. Overall expression and secretion of cytokines is dependent, at least in part, on genetic polymorphism (nucleotide variations) within the promoter region or other regulatory sequences of cytokine genes. The majority of polymorphisms described are single nucleotide polymorphism (SNPs). The objective of this study was to analyze the genetic profile of Th1 and Th2 cytokines in 30 Iranian patients with CML and 40 healthy subjects. Methods: In the patients and control subjects, the allelic and genotype frequencies were determined for the cytokine genes. All typing were performed by PCR-SSP assay. Allele and genotype frequencies were calculated and compared with those of normal controls. Results: The results showed that the most frequent alleles in our patients were TGF-b TG/TG, IL-4 T at position -1089, C at position -590, T at position -33 and IL-10 A at position -1082. Whereas the following alleles - TGF-b CG/CG and IL-10 C at position -592 – were seen in much lower frequencies. Conclusion: In conclusion, it could be suggested that the frequency of high producing TGF-b alleles and low producing IL-4 and IL-10 alleles in the CML patients is higher than the normal subjects.