Yaghoub Mollaei-Kandelous; Pedram Ahmadpoor; Mohsen Nafar; Mohammad Reza Khatami; Samad Farashi Bonab; Nader Tajik; Mahdi Shekarabi; Aliakbar Amirzargar
Abstract
Background: Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies.Objective: ...
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Background: Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies.Objective: This study aimed to evaluate prospectively the influence of low dose ATG induction therapy with two different protocols (Sirolimus versus Mycophenolate mofetil) on the expression of functional markers (LAG-3, CD39, and intracellular CTLA-4) on conventional Tregs in renal recipients.Methods: Thirty-eight renal transplant recipients were enrolled in this study. The patients were randomly assigned into two groups, including TMP: Tacrolimus (Tac), Mycophenolate mofetil (MMF), and Prednisolone (n=23); and TSP: Tac, Sirolimus (SRL), and Prednisolone (n=15). The frequency of LAG-3, CD39, and intracellular CTLA-4 on circulating Tregs was analyzed by flow cytometry before and after transplantation.Results: Analysis of the flow cytometry data showed that the frequency of CD4+CD25+FOXP3+ Tregs increased 4 months post-transplantation compared to pre-transplantation in both groups, although this increase was only significant in TMP group. In TMP treated patients, the frequency of LAG-3+ Tregs and CD39+ Tregs increased, whereas the frequency of intracellular CTLA-4+ Tregs decreased 4 months post-transplantation. In TSP group, while the frequency of CD39+ Tregs increased, the frequency of CTLA-4+ Tregs decreased in post-transplantation compared to pre-transplantation.Conclusions: it seems that both treatment regimen protocols with a low dose ATG induction therapy may be clinically applicable in kidney transplant recipients.
Amir Hossein Mansourabadi; Mona Sadeghalvad; Hamid-Reza Mohammadimotlagh; Aliakbar Amirzargar
Abstract
The COVID-19 pandemic is probably the most devastating worldwide challenge in recent century. COVID-19 leads to a mild to severe respiratory disease and affects different organs and has become a global concern since December 2019. Meanwhile, molecular biology and diagnostic laboratories played an essential ...
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The COVID-19 pandemic is probably the most devastating worldwide challenge in recent century. COVID-19 leads to a mild to severe respiratory disease and affects different organs and has become a global concern since December 2019. Meanwhile, molecular biology and diagnostic laboratories played an essential role in diagnosis of the disease by introducing serological and molecular tests. Molecular-based techniques are reliable detection tools for SARS-CoV-2 and used for diagnosis of patients especially in the early stage of the disease. While, serological assays are considered as additional tools to verify the asymptomatic infections, tracing previous contacts of individuals, vaccine efficacy, and study the seroprevalance. The average time of the appearance of anti-SARS-CoV-2 antibodies in the patient's serum is 3-6 days after the onset of symptoms for both IgM and IgA and 10-18 days for IgG. Following the outbreak of COVID-19, FDA has approved and authorized a series of serological laboratory tests for early diagnosis. Serological assays have low-cost and provide fast results but have poor sensitivity in the early stage of the viral infection. Although the serological tests may not play an important role in the active case of COVID-19, it could be effective to determine the immunity of health care workers, and confirm late COVID-19 cases during the outbreak. In this review, we compared various laboratory diagnostic assays for COVID-19.
mahdi aminikhah; Mir Saeed Yekaninejad; M.Hosein Nicknam; Farideh Khosravi; Mehrnaz naroei nejad; Bita Ansaripour; batol moradi; Behrouz Nikbin; Aliakbar Amirzargar
Abstract
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 ...
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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.
Zahra Mehraji; Ali Farazmand; Alireza Esteghamati; Sina Noshad; Maryam Sadr; Somayeh Amirzargar; Mir Saeed Yekaninejad; Aliakbar Amirzargar
Volume 14, Issue 3 , September 2017, , Pages 223-230
Abstract
Background: Graves’ disease (GD), a highly rampant autoimmune disorder of the thyroid gland, is responsible for 60-80% of the clinical cases of hyperthyroidism. Over the past decades, genetic association studies have identified several GD susceptibility loci in CTLA-4, TSHR and major histocompatibility ...
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Background: Graves’ disease (GD), a highly rampant autoimmune disorder of the thyroid gland, is responsible for 60-80% of the clinical cases of hyperthyroidism. Over the past decades, genetic association studies have identified several GD susceptibility loci in CTLA-4, TSHR and major histocompatibility complex regions. The information on the association between the human leukocyte antigens (HLA) and GD among Iranians is scarce. Objective: To identify HLA polymorphisms that might confer susceptibility or protect against GD. Methods: Eighty unrelated patients with a confirmed diagnosis of GD were included in the case group. The control group consisted of 180 unrelated healthy individuals with normal thyroid function tests. The polymerase chain reaction with sequence specific primers (PCR-SSP) method was used for HLA typing. Results: Frequencies of HLA-A*68 (15.6% vs. 4.2%, p=0.004) and B*08 (8.8% vs. 2.5, p=0.030) were significantly higher in patients with GD compared with healthy controls. No patients with GD had HLA-A*33, whereas it was found in 7.0% of the controls (p=0.011). HLA-DQB1*0201 was significantly less frequent among patients with GD (15.6% vs. 26.8%, p=0.040). Additionally, patients with GD were significantly less bound to have HLA-DQA1*0201 (6.2% vs. 15.1%, p=0.045). Concerning allelic distributions, no noticeable difference was found between GD patients with and without Graves’ ophthalmopathy (p>0.05 in all cases). Conclusion: In the Iranian population, HLA-A*68 and -B*08 confer susceptibility to GD, whereas HLA-A*33, -DQB1*0201, and -DQA1*0201 appear to have protective roles.
Morteza Hosseinzadeh; Mohsen Nafar; Pedram Ahmadpoor; Farshid Noorbakhsh; Mir Saeed Yekaninejad; Mohammad Hossein Niknam; Aliakbar Amirzargar
Volume 14, Issue 1 , March 2017, , Pages 24-34
Abstract
Background: The incidence of ischemic reperfusion injury (IRI) in early phase post-transplantation and activation of toll-like receptor (TLR-2) and TLR-4 remarkably impact the outcome of a renal allograft. Objective: To investigate whether the expression of TLRs in peripheral blood mononuclear cells ...
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Background: The incidence of ischemic reperfusion injury (IRI) in early phase post-transplantation and activation of toll-like receptor (TLR-2) and TLR-4 remarkably impact the outcome of a renal allograft. Objective: To investigate whether the expression of TLRs in peripheral blood mononuclear cells (PBMCs) can predict the clinical outcome of kidney allografts. Methods: We obtained blood samples from 52 renal transplant patients before transplant, and 2, 90, and 180 days post-transplantation in order to analyze the surface expressions of TLR-2 and TLR-4 on peripheral blood monocytes. The expression patterns of TLR-2 and TLR-4 were compared between patients with graft dysfunction (GD) and those with well-functioning graft (WFG). Results: Significantly different mean dynamic changes in surface expression of TLR-2, according to percentage of TLR-2+ cells, between (the GD and WFG) groups existed at most time-points before and after renal transplantation (p=0.007) with the exception of day 2 post-transplantation. We observed significantly higher mean fluorescence intensities of TLR-2 and TLR-4 on CD14+ cells in the GD group compared to the WFG group. This finding was particularly observed 180 days post-transplantation (p=0.001). Based on TLR-2 and TLR-4 protein expression for each step, multiple logistic regression and ROC curve analysis revealed that an increase in CD14+ TLR-2+ monocytes within the 90 days post-transplantaton was associated with increased risk of GD at 180 and 365 days post-transplantation [odds ratio (OR)=1.27, p=0.005)]. Conclusion: Sequential monitoring of TLR-2 and TLR-4 expression patterns in peripheral blood monocytes appear to be prognostic and predictive biomarkers for early and late kidney allograft outcomes.
Zeinab Kadkhoda; Aliakbar Amirzargar; Zahra Esmaili; Mahdi Vojdanian; Solmaz Akbari
Volume 13, Issue 3 , September 2016, , Pages 197-203
Abstract
Background: Periodontitis and rheumatoid arthritis (RA) share a number of clinical and pathologic features, one of which is the presence of the tumor necrosis factor alpha (TNF-α)-induced bone resorption that is involved in the pathogenesis of both. Objectives: To investigate the effect of TNF-α ...
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Background: Periodontitis and rheumatoid arthritis (RA) share a number of clinical and pathologic features, one of which is the presence of the tumor necrosis factor alpha (TNF-α)-induced bone resorption that is involved in the pathogenesis of both. Objectives: To investigate the effect of TNF-α blockade on periodontal conditions in patients with active RA. Method: The periodontal statuses of 36 patients (26 females, 10 males) diagnosed with active RA were evaluated both before and after anti-TNF-α therapy. Gingival index, bleeding on probing (BOP), probing pocket depth (PPD), oral hygiene index (OHI), and levels of TNF-α in gingival crevicular fluid (GCF) were measured at the baseline and 6 weeks after the treatment. Wilcoxon signed ranked test was used for statistical analyses. Results: Based on OHI (p=0.860), the level of plaque control did not change during the study period, but there was a significant reduction in gingival inflammation based on the mean BOP (p=0.049) and GI (p=0.036) before and after 6 weeks of anti-TNF-α therapy. The mean PPD index did not significantly differ at the baseline and 6 weeks after treatment (p=0.126). Conclusion: Anti-TNF-α therapy might have a desirable effect on periodontal conditions and might reduce TNF-α level in GCF of patients with RA.
Babak Aghili; Ali Akbar Amirzargar; Asadollah Rajab; Ali Rabbani; Arya Sotoudeh; Sara Assadiasl; Bagher Larijani; Ahmad Massoud
Volume 12, Issue 4 , December 2015, , Pages 240-251
Abstract
Background: Type 1 diabetes (T1D) is a T cell mediated autoimmune disease targeting the insulin-producing β cells within pancreatic islets. Autoimmune diseases may develop as a consequence of altered balance between regulatory (Tregs) and autoreactive T cells. Objectives: To evaluate Treg cells ...
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Background: Type 1 diabetes (T1D) is a T cell mediated autoimmune disease targeting the insulin-producing β cells within pancreatic islets. Autoimmune diseases may develop as a consequence of altered balance between regulatory (Tregs) and autoreactive T cells. Objectives: To evaluate Treg cells frequency and suppressive function in the peripheral blood of newly diagnosed T1D patients in comparison with healthy controls. Methods: Fifteen new cases of T1D patients and 15 age- and sexmatched healthy controls were recruited to this study. Their peripheral blood mononuclear cells (PBMCs) were isolated and CD4 +CD25+FoxP3+CD127-/low Treg cells were studied by flowcytometry technique. Thereafter, Tregs were isolated by Magnetic- Activated Cell Separation (MACS) technology and by using CFSE (carboxyfluorescein succinimidyl ester) dilution assay, their suppressive activity was evaluated in the coculture of CD4 +CD25- T responder cells with Treg cells. Results: The percentage of CD4 +CD25+FoxP3+CD127-/low Tregs did not differ between T1D patients and healthy controls but the MFI (mean fluorescence intensity) of transcription factor FoxP3 (forkhead box protein P3) was significantly decreased in T1D patients (20.03 ± 1.4 vs. 31.33 ± 2.95, p=0.0017). Moreover, the suppressive function of CD4 +CD25+CD127-/low Treg cells was significantly diminished in T1D patients in comparison with control group (35.16 ± 4.93% vs. 60.45 ± 5.26%, respectively, p=0.0015). Conclusion: Present study indicates an impaired immune regulation among T1D patients, characterized by defects in suppressive function and expression of FoxP3 in Treg cells without any significant decrease in their frequency in peripheral blood.
Atefeh Kamallou; Mahbobeh Haji Abdolbaghi; Minoo Mohraz; Mernaz Rasolinejad; Ehsan Karbasi; Bita Ansaripour; Samaneh Soltani; Arezou Rezaei; Neda Khalili; Aliakbar Amirzargar
Volume 11, Issue 4 , December 2014, , Pages 221-232
Abstract
Background: Lymphocyte subsets enumeration is considered prominent in the management of primary and acquired immunodeficiency disorders. Because of local variations due to race, age, gender, and environmental conditions on lymphocyte subsets, and to improve the accuracy of interpretation of laboratory ...
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Background: Lymphocyte subsets enumeration is considered prominent in the management of primary and acquired immunodeficiency disorders. Because of local variations due to race, age, gender, and environmental conditions on lymphocyte subsets, and to improve the accuracy of interpretation of laboratory findings, reference intervals must be determined in every population. Objective: To establish a normal reference range for CD3+ , CD4+ , CD8+ , CD19+ and CD56+ lymphocytes in a healthy Iranian adult population using flowcytometry. Method: Blood samples were collected from 221 HIV seronegative individuals, including 112 females and 109 males, with ages ranging from 20 to 40 years old. The percentage of lymphocytes expressing either of CD3, CD4, CD8, CD19 and CD56 surface markers were determined by flowcytometry assay. Result: Total mean percentage and absolute count of lymphocyte subsets were as follows: CD3+ : 70.90 ± 7.54%, 1800.87 ± 471.09 cells/µl; CD4+ : 41.04 ± 7.86%, 1039.99 ± 338.02 cells/µl; CD8+ : 31.11 ± 6.60%, 783.95 ± 234.87 cells/µl; CD19+ : 12.77 ± 4.56%, 328.37 ± 153.17 cells/µl; CD56+ : 15.53 ± 6.34%, 388.62 ± 176.17 cells/µl, respectively. The ratio of CD4+ /CD8+ lymphocytes for the studied population was 1.39 ± 0.48. Significant differences were observed between male and female subjects indicating that the average percentage of CD3+ cells (p=0.017) and CD4+ T cells (p=0.003) were higher in the female population, whereas the average percentage of CD19+ cells (p=0.02) tended to be higher among males. However, investigations on the CD56+ NK cell and CD8+ T cell sub-populations did not show any statistical differences between the two genders. In comparison with reports of other populations, we were confronted with different results. Conclusion: Establishing reference values of lymphocyte subsets for each population is helpful in achieving standard criteria for the prognosis of HIV infection. Therefore, normal ranges established by this survey can be used as a reference for decisions made in clinical practice.
Sara Assadiasl; Pedram Ahmadpoor; Mohsen Nafar; Mahboob Lessan Pezeshki; Fateme Pourrezagholi; Mahmoud Parvin; Abtin Shahlaee; Adel Sepanjnia; Mohammad Hossein Nicknam; Aliakbar Amirzargar
Volume 11, Issue 3 , September 2014, , Pages 139-152
Abstract
Background: Regulatory T cells have been suggested to have a protective role against acute rejection in allograft recipients. However, there is little information available about their contribution to chronic rejection process. The role of transforming growth factor-beta 1 (TGF- β1) as a profibrogenic ...
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Background: Regulatory T cells have been suggested to have a protective role against acute rejection in allograft recipients. However, there is little information available about their contribution to chronic rejection process. The role of transforming growth factor-beta 1 (TGF- β1) as a profibrogenic and/or immunoregulatory cytokine in renal allografts is also controversial. Objectives: To evaluate the frequency of CD4+CD25+CD127- and CD3+CD8+CD28- regulatory T cells in chronic allograft dysfunction (CAD) and to investigate the expression of TGF- β1 in renal allografts. Methods: Thirty biopsy-proven CAD patients were pair-matched with 30 stable graft function patients and a third group of healthy volunteers. Flowcytometry was performed on PBMCs to determine the frequency of CD3+CD8+CD28- and CD4+CD25+CD127- regulatory T cells in lymphocyt population. TGF- β1 gene expression was assessed by Real Time PCR. Results: The percentage of CD3+CD8+CD28- Tregs among renal allograft recipients was higher than healthy controls (p<0.001) since stable graft patients showed the most rates. The frequency of CD4+CD25+CD127- Tregs was lower in CAD patients than stable recipients (p=0.024) and healthy group (p=0.015). TGF- β1 gene expression was greater in CAD patients compared to healthy group (p=0.03) but there was no significant difference between gene expression of stable graft patients and healthy volunteers. Conclusion: The negative association between the frequency of regulatory T cell subtypes and chronic allograft dysfunction proposes these cells as probable candidates for promoting allograft survival. Moreover, despite the immunoregulatory capacity of TGF- β1, it is likely to be implicated in chronic damages of allograft tissue.
Nafiseh Esmaili; Hossein Mortazavi; Sheyda Chams-Davatchi; Maryam Daneshpazhoooh; Maede Rayati Damavandi; Zeinab Aryanian; Ali Akbar Amirzargar
Volume 10, Issue 1 , March 2013, , Pages 1-9
Abstract
Background: A common Human Leukocyte Antigen (HLA) class II allele, DQβ1*03:01, seems to be associated with Bullous pemphigoid (BP) in Caucasians whereas previous studies in other ethnic groups showed other HLA class II alleles as genetic predisposing factors for BP. Objective: To investigate the ...
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Background: A common Human Leukocyte Antigen (HLA) class II allele, DQβ1*03:01, seems to be associated with Bullous pemphigoid (BP) in Caucasians whereas previous studies in other ethnic groups showed other HLA class II alleles as genetic predisposing factors for BP. Objective: To investigate the association of HLA class II alleles and haplotypes with BP in Iranian population. Methods: Fifty patients with Bullous pemphigoid and 180 geographically matched, healthy individuals as control group enrolled into this study. HLA typing of class II (DR and DQ alleles) was carried out using polymerase chain reaction based on sequence-specific primers method. Results: Class II DQA1 and DQB1 typing showed a significantly higher frequency of HLA-DQA1*05:01 (45% vs. 33%, p=0.03), HLA-DQB1*03:01 (36% vs. 23.6%, p=0.02) and HLA-DQB1*04:01 (4% vs. 1.6%, p=0.04) in the BP patients compared with controls. For DRB1 allele frequencies, there were no significant disease associations. The frequency of DRB1*08:01/DQA1*05:01/DQB1*03:01 (3% vs. 0%, p=0.02) haplotype showed an increase among patients compared with controls. Conclusion: Our data suggest that Iranian patients with BP present the same genetic predisposition linked to HLA-DQB1*03:01 previously reported in Caucasians.
Ghasem Solgi; Gholamreza Pourmand; Abdorasool Mehrsai; Mohsen Tahei-mahmoudi; Mohammad Hossein Nicknam; Mohammad Ebrahimi Rad; Ali Seraji; Amirabbas Asadpoor; Bita Ansaripor; Behrouz Nikbin; Aliakbar Amirzargar
Volume 7, Issue 1 , March 2010, , Pages 18-29
Abstract
Background: Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients. Objective: The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concur-rent donor bone marrow cell infusion ...
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Background: Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients. Objective: The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concur-rent donor bone marrow cell infusion (DBMI). Methods: Between June 2006 and May 2007, forty living unrelated donor kidney transplants consisting of 20 recipients with DBMI and 20 without infusion entered into the study and were monitored prospectively for one year. Pre- and post-transplant (days 14, 30, and 90) sera were screened for the presence of anti-HLA class-I and II antibodies, and subsequently positive sera retested with ELISA spe-cific panel for antibody specification. Results: Of 40 patients, 9 (22.5%) experienced acute rejection episodes (ARE) (6/20 cases in non-infused versus 3/20 in DBMI patients). The prevalence of anti-HLA antibodies before and after transplantation were higher in patients with ARE compared to non-rejecting ones (88.8% vs. 38.7%, p=0.01 and 66.6% vs. 25.8%, p=0.04, respectively). A total of 10% (4/40) of patients developed donor specific anti-HLA antibodies (DSA) and in this regard 2 patients from the control group experienced ARE. All 3 rejecting patients in DBMI group were negative for DSA and positive for non-DSA. The lower titer of post-transplant anti-HLA antibodies were shown in DBMI patients compared to pre-transplantation titer. Additionally, the average serum creatinine levels during one year follow up and even in those patients with ARE were lower compared to controls. Con-clusion: Our findings reveal an association between pre- and post-transplant anti-HLA an-tibodies, and ARE and also early allograft dysfunction. It suggests that lower incidence of ARE, undetectable DSA, lower titer of antibodies concomitant with a decrease in serum creatinine level, better allograft function and lower percentages of PRA in DBMI patients, could be the probable manifestations of partial hypo-responsiveness against allografts.
Ali Akbar Amirzargar; Nilufar Mohseni; Mohammad Ali Shokrgozar; Zohreh Arjang; Nahid Ahmadi; Manijeh Yousefi Behzadi; Amir Amanzadeh; Fazel Shokri
Abstract
Background: Different studies have demonstrated that a small proportion of healthy individuals receiving the hepatitis B (HB) vaccine do not produce protective levels of anti-HB antibody, a phenomenon which could be linked to certain human leukocyte an-tigen (HLA) class-II alleles or haplotypes. Objectives: ...
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Background: Different studies have demonstrated that a small proportion of healthy individuals receiving the hepatitis B (HB) vaccine do not produce protective levels of anti-HB antibody, a phenomenon which could be linked to certain human leukocyte an-tigen (HLA) class-II alleles or haplotypes. Objectives: The present study was under-taken to determine the frequency of HLA class-II alleles in Iranian healthy adult re-sponders and non-responders to HB vaccine. Methods: Twelve non-responders (anti-HBs antibody<10 IU/L) and 46 responders (anti-HBs antibody>100 IU/L) were tissue typed for HLA class-II. HLA-DRB1, DQB1 and DQA1 alleles were determined using polymerase chain reaction based on sequence specific primers (PCR-SSP) technique. Accessibility to excess amount of genomic DNA was possible using Epstein-Barr virus (EBV)-transformed B-cells established from all vaccinees. Results: Our results demon-strated increased frequencies of HLA- DRB1*07, DRB1*03, DRB1*04, DQB1*0201, DQA1*0201 alleles and HLA- DRB1*07/DQB1*0201/DQA1*0201 and DRB1*04/DQB1*0302/DQA1*03011 haplotypes in the non-responder group. Com-parison between responders and non-responders revealed only a significant difference for DQB1*0201 allele (p<0.05). Conclusion: These findings confirm the association of certain HLA alleles and haplotypes with the lack of antibody response to HB vaccine in an Iranian population.
Abdol Rahim Nikzamir; Taghi Golmohammadi; Manouchehr Nakhjavani; Mahine Zahraei; Ali Akbar Amirzargar
Volume 3, Issue 1 , March 2006, , Pages 23-29
Abstract
Background: Angiotensin I converting enzyme (ACE) is a Zinc metalloproteinase, converts Ang-I to Ang- II, a pro-inflammatory agent which may contribute to pathophysiology of some diseases like type 2 diabetes. Objective: To investigate the relationship between ACE I/D polymorphism and type 2 diabetes ...
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Background: Angiotensin I converting enzyme (ACE) is a Zinc metalloproteinase, converts Ang-I to Ang- II, a pro-inflammatory agent which may contribute to pathophysiology of some diseases like type 2 diabetes. Objective: To investigate the relationship between ACE I/D polymorphism and type 2 diabetes in 261 Iranian casecontrol pairs. Methods: 170 patients (85 type 2 diabetics with nephropathy and 85 type 2 diabetics without nephropathy) and 91 healthy control subjects were enrolled in our study. I/D polymorphism of the ACE gene was detected by polymerase chain reaction (PCR) utilizing specific primers. Results: The frequency of DD genotype in the DN group was higher than that of the type 2 diabetic patients (30.6% vs. 20%, P =0.157) and the control group (30.6% vs. 14.3%, P=0.006). The frequency of D allele in nephropathic patients was 58.2% as compared to type 2 diabetic patients without nephropathy 50.5% (P=0.19) and control subjects 37.3% (P =0.001). Therefore, the frequency of DD genotype and D allele significantly increased in DN patients in comparison to healthy controls. Conclusion: It is concluded that the DD genotype and/or D allele of ACE gene may increase the risk for type 2 diabetes but not diabetic nephropathy.
Asghar Aghamohammadi; Ali Akbar Amirzargar; Nima Parvaneh; Paul Marjousef; Mostafa Moin; Abdolhassan Farhoudi; Mehdi Yeganeh; Toshio Miyawaki
Volume 2, Issue 4 , December 2005, , Pages 201-207
Abstract
Background: The B-cell defect in X-linked agammaglobulinemia (XLA) is caused by mutations in the gene for Bruton's tyrosine kinase (BTK). BTK mutations result in deficient expression of BTK protein in peripheral blood monocytes. Methods: Using the anti-BTK monoclonal antibody (48-2H), a flow cytometric ...
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Background: The B-cell defect in X-linked agammaglobulinemia (XLA) is caused by mutations in the gene for Bruton's tyrosine kinase (BTK). BTK mutations result in deficient expression of BTK protein in peripheral blood monocytes. Methods: Using the anti-BTK monoclonal antibody (48-2H), a flow cytometric analysis of intra cytoplasmic BTK protein expression in monocytes was performed to identify Iranian patients with XLA phenotype. To examine the possible identification of XLA patients and female carriers by this assay, we studied 13 XLA families. Results: The flow cytometric assay showed deficient expression of the BTK protein in 12 (92%) families. One patient exhibited a normal level of BTK expression. The cellular mosaicism of BTK expression in monocytes from obligate carriers was clearly shown in 9 of 12 (75%) families. Conclusion: The results suggested that most XLA patients have deficient expression of the BTK protein; therefore we conclude that deficient expression of BTK protein can be evaluated by a flow cytometric assay.
Mahboob Lessan-Pezeshki; Ali Akbar Amirzargar; Nooshin Golabi; Mohammadreza Khatami; Behzad Einollahi; Vahid Pourfarziani; Farideh Khosravi; Hassaneh Tajerzadeh; Behrouz Nikbin
Volume 2, Issue 2 , June 2005, , Pages 87-90
Abstract
Background: Monitoring of phenotypic characteristics of T-lymphocytes in peripheral blood is commonly performed to give the clinical parameters in the management of kidney transplant recipients. Objective: To predict rejection in renal transplantation by immune parameters. Methods: 16 non-diabetic ...
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Background: Monitoring of phenotypic characteristics of T-lymphocytes in peripheral blood is commonly performed to give the clinical parameters in the management of kidney transplant recipients. Objective: To predict rejection in renal transplantation by immune parameters. 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.
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.
Behrouz Nikbin; Nader Tajik; Ali Saraji; Gholam Reza Pourmand; Fatemeh Talebian; Abdurasul Mehrsai; Ali Akbar Amirzargar
Volume 1, Issue 3 , December 2004, , Pages 162-168
Abstract
Background: The Presence of donor leukocytes in recipients of organ allograft has been shown even several years after transplantation. However, it remains unclear whether this donor cell microchimerism plays an effective role in allograft acceptance or is simply a consequence of immunosuppressive conditions ...
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Background: The Presence of donor leukocytes in recipients of organ allograft has been shown even several years after transplantation. However, it remains unclear whether this donor cell microchimerism plays an effective role in allograft acceptance or is simply a consequence of immunosuppressive conditions in recipients. Objective: To study microchimerism in a group of kidney transplant recipients. Methods: In this study, the Peripheral Blood Microchimerism (PBM) after renal transplantation was retrospectively evaluated in 32 male-to-female recipients of living (unrelated) and cadaveric donor renal transplants. Using a Nested Polymerase Chain Reaction (Nested-PCR) amplification specific for SRY region of the Y chromosome, microchimerism was detected with a sensitivity of 1:1000000. Recipients were classified and compared according to the presence of PBM, acute and chronic rejection episodes, type of allotransplant, recipient and donor age at transplantation, previous male labor or blood transfusion, allograft function (serum creatinine level), and body mass index. Results: Among 32 recipients, 7 (21.9) were positive for PBM in multiple testing at different post-transplantation times. All microchimeric recipients had received kidney from living-unrelated donors. No significant difference was observed with regard to other parameters mentioned above. In addition, acute rejection rate in the microchimeric group was 3 (42%) versus 4 (16%) in the nonmicrochimeric recipients (not significant). Conclusion: Our results demonstrate better establishment of microchimerism after living donor kidney transplantation. However, concerning the true effect of microchimerism after renal transplantation doubt still persists; and it seems that microchimerism alone has no major protective role in renal allograft survival.
Ali Akbar Amirzargar; Abdol Ali Danesh; Farideh Khosravi; Mohammad Hossein Niknam; Behrouz Nikbin
Volume 1, Issue 2 , September 2004, , Pages 125-129
Abstract
Background: Pulmonary tuberculosis (PTB) has recently become a major problem in developed countries especially in immune compromised HIV infected individuals. Cytokines, their genes and receptors have been implicated in the protective immunity, pathophysiology and development of tuberculosis. ...
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Background: Pulmonary tuberculosis (PTB) has recently become a major problem in developed countries especially in immune compromised HIV infected individuals. Cytokines, their genes and receptors have been implicated in the protective immunity, pathophysiology and development of tuberculosis. Material & 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-1¾ (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- ¾ (C/T codon 10, G/C codon 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 polymorphism where the C allele was over presented in the PTB patients (60% vs. 37.5%, P = 0.04). A significant negative association at codon 10 TGF- ¾ 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 TGF- ¾ production. For TNF ¿ an insignificant tendency was found at position -308 A/G polymorphism where the G allele carried by 80% of cases and 65% of controls (P = 0.07). At position -238 a negative association was found at the GA polymorphism (10% vs. 25%, P = 0.07). For IL-6 an insignificant positive association at position -174 C/G polymorphism, 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- ¾ decreases in PTB patients.
Ali Rafinejad; Mohammad Hossein Niknam; Ali Akbar Amirzargar; Farideh Khosravi; Forouzan Karimi; Bagher Larijani
Volume 1, Issue 2 , September 2004, , Pages 130-132
Abstract
Background: Type 1 Diabetes (T1D) is a chronic and progressive autoimmune disorder. Cytokines play a critical role in the pathogenesis of T1D. Objective: IFN-¹ polymorphism was investigated in T1D and compared with normal controls. Methods: Thirty patients suffering from T1D and 40 ...
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Background: Type 1 Diabetes (T1D) is a chronic and progressive autoimmune disorder. Cytokines play a critical role in the pathogenesis of T1D. Objective: IFN-¹ polymorphism was investigated in T1D and compared with normal controls. Methods: Thirty patients suffering from T1D and 40 normal controls were studied simultaneously using PCR technique. IFN- ¹ gene was evaluated at position 5’UTR +5644. Results: There was a significant difference between patient and control groups in TT genotype (P<0.05). Conclusion: In this study, we found a negative association between IFN-¹ gene at position 5’UTR +5644 and T1D in Iranian patients pointing to T allele as a protective factor against T1D.
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.