Publications by authors named "Aliakbar Amirzargar"

66 Publications

Association of HLA Class II Alleles with Disease Severity and Treatment Response in Iranian Patients with Myasthenia Gravis.

J Neuromuscul Dis 2021 May 26. Epub 2021 May 26.

Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Myasthenia gravis is an autoimmune neuromuscular disease with a multifactorial etiology. A major part of the genetic susceptibility belongs to the HLA encoding genes. In this study, we investigated the role of HLA class II polymorphism in disease severity, and treatment response. In our 146 patients, 15 DRB1, 7 DQA1, and 9 DQB1 alleles, and 19 haplotypes were found. Adjusted p-values did not show any significant associations between these loci, disease severity and treatment outcome. Further studies in different populations with a larger number of patients are needed to determine the exact contribution of HLA class II alleles to MG prognosis.
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http://dx.doi.org/10.3233/JND-210700DOI Listing
May 2021

Cell therapy in transplantation: A comprehensive review of the current applications of cell therapy in transplant patients with the focus on Tregs, CAR Tregs, and Mesenchymal stem cells.

Int Immunopharmacol 2021 May 6;97:107669. Epub 2021 May 6.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, 009821 Tehran, Iran. Electronic address:

Organ transplantation is a practical treatment for patients with end-stage organ failure. Despite the advances in short-term graft survival, long-term graft survival remains the main challenge considering the increased mortality and morbidity associated with chronic rejection and the toxicity of immunosuppressive drugs. Since a novel therapeutic strategy to induce allograft tolerance seems urgent, focusing on developing novel and safe approaches to prolong graft survival is one of the main goals of transplant investigators. Researchers in the field of organ transplantation are interested in suppressing or optimizing the immune responses by focusing on immune cells including mesenchymal stem cells (MSCs), polyclonal regulatory Tcells (Tregs), and antigen-specific Tregs engineered with chimeric antigen receptors (CAR Tregs). We review the mechanistic pathways, phenotypic and functional characteristics of these cells, and their promising application in organ transplantation.
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http://dx.doi.org/10.1016/j.intimp.2021.107669DOI Listing
May 2021

Serological and Molecular Tests for COVID-19: a recent update.

Iran J Immunol 2021 Mar;18(1):13-33

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

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.
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http://dx.doi.org/10.22034/iji.2021.88660.1894DOI Listing
March 2021

Investigating the Role of BAFF and Its Receptors in Renal Transplant Recipients with Chronic Antibody-Mediated Rejection.

J Immunol Res 2021 6;2021:6654992. Epub 2021 Mar 6.

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

Background: Kidney transplantation is the best treatment option for end stage renal disease (ESRD), but graft rejection is still a big obstacle that occurs in spite of immunosuppressive therapy. B cells are considered as the major reason for renal graft rejection because of antibody production. Due to their roles in B cell function, we intended to evaluate the B cell activating factor (BAFF) and its receptors including BAFF receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and cyclophilin ligand interactor (TACI) in renal transplant patients.

Method: The study included 40 kidney allograft patients with cAMR, 40 stable kidney allograft patients, and 8 healthy volunteers with normal kidney function. The percentage and absolute number of CD19 B cells were analyzed by flow cytometry, the serum level of BAFF was analyzed by ELISA, and mRNA expressions of BAFF and BAFF receptors (BAFF-R, BCMA, and TACI) were measured using quantitative real-time PCR.

Results: The percentage and the absolute number of B cells decreased significantly in stable and cAMR patients compared to healthy individuals. The serum level and gene expression of BAFF, as well as the mRNA level of BCMA, were increased significantly in both cAMR and stable patients compared to healthy volunteers. There was an overexpression of TACI mRNA in cAMR patients compared to stable patients.

Conclusions: Both soluble protein and mRNA transcript of BAFF increased in transplant recipients. However, BAFF neither at the serum level nor at the mRNA transcript level cannot be a good biomarker for the prediction of cAMR. In addition, expression of TACI, compared to other receptors of BAFF, confers a potential to be used in distinguishing cAMR and stable kidney transplant patients.
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http://dx.doi.org/10.1155/2021/6654992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959970PMC
March 2021

Intravenous Immunoglobulin Therapy in Myocarditis.

Iran J Allergy Asthma Immunol 2020 Aug 25;19(4):323-336. Epub 2020 Aug 25.

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

Myocarditis is an inflammatory disease of the myocardium with lymphocyte infiltration and myocyte necrosis leading to a wide range of clinical presentations including heart failure, arrhythmia, and cardiogenic shock. Infectious and noninfectious agents may trigger the disease. The fact that immunosuppressive drugs are useful in several kinds of autoimmune myocarditis is proof of the autoimmune mechanisms involved in the development of myocarditis. Pathogenic mechanisms in myocardial inflammation are including inflammasome activation followed by myocyte destruction, myocarditis, and pericarditis. Intravenous immunoglobulin (IVIG) is a serum product made up of immunoglobulins, widely used in a variety of diseases. This product is effective in several immune-mediated pathologies. As well as the determined usage of IVIG in Kawasaki disease, IVIG may be useful in several kinds of heart failure including fulminant myocarditis, acute inflammatory cardiomyopathy, Giant Cell Myocarditis, and peripartum cardiomyopathy. Generally, IVIG is used in two different doses of low dose (200 to 400 mg/kg) and high dose (2 g/kg) regimen. The exact therapeutic effects of IVIG are not clear, however over the last decades, our knowledge about its mechanism of function has greatly enhanced. IVIG administration should be based on the accepted protocols of its transfusion. In this review article, we try to provide an overview of the different kinds of myocarditis, pathologic mechanisms and their common treatments and evaluation of the administration of IVIG in these diseases. Furthermore, we will review current protocols using IVIG in each disease individually.
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http://dx.doi.org/10.18502/ijaai.v19i4.4109DOI Listing
August 2020

B cell modulation strategies in the improvement of transplantation outcomes.

Mol Immunol 2020 09 15;125:140-150. Epub 2020 Jul 15.

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

Successful transplantation outcome is the final goal in most end stage and nonfunctional organs; however, despite using different therapeutic strategies, antibody-mediated rejection is still a big obstacle. B cells have a key role in transplant rejection by several functions, such as antibody production, antigen presenting, contribution in T cell activation, forming the germinal center, and tertiary lymphoid organs. Therefore, B cells modulation seems to be very crucial in transplant outcome. A double-edged sword function is considered for B cells during transplantation; On the one hand, antibody production against the transplanted organ induces antibody-mediated rejection. On the other hand, IL10 production by regulatory B (Breg) cells induces graft tolerance. Nowadays, several monoclonal antibodies (mAb) are available for B cell modulation that are routinely used in transplant recipients, among which rituximab (anti-CD20 mAb) act in eliminating B cells. However, there are some other monoclonal antibodies, such as epratuzumab and Inotuzumab ozogamicin (IO), which exert anti-CD22 activity, resulting in disruption of B cell functions and induction of tolerance in autoimmune disease or B cell malignancies; that notwithstanding, these mAbs have not yet been tried in transplantation. In this review, we focus on different methods for modulating the activity of B cells as well as induction of Breg cells, aiming to prevent the allograft rejection.
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http://dx.doi.org/10.1016/j.molimm.2020.06.028DOI Listing
September 2020

Human leukocyte antigen class I (A, B) and class II (DRB1) allele and haplotype frequencies in Iranian patients with Buerger's disease.

Immun Inflamm Dis 2020 09 21;8(3):434-440. Epub 2020 Jun 21.

Department of Vascular Surgery, Sina Hospital, Tehran University of Medical Science, Tehran, Iran.

Objective: The aim of this study was to investigate the human leukocyte antigen (HLA) class I (HLA-A and HLA-B) and II (HLA-DRB1) allele and haplotype frequencies in a group of Iranian patients with Buerger's disease (BD) in comparison with a normal healthy control group.

Methods: A total of 70 unrelated male patients and 100 healthy controls from Sina Hospital, Tehran, Iran, belonging to the same ethnic background, were enrolled in this case-control study. HLA-A, B, and DRB1 typing were performed by polymerase chain reaction with sequence-specific primers (PCR-SSP).

Results: The results of this case-control study showed that the frequency of the HLA-A*03:01 (odds ratio (OR) = 2.88, P value (Pv) = .002), HLA-A*29:01 (OR = 15.31, Pv < .001), HLA-DRB1*04:02 (OR = 3.41, Pv < .001), and HLA-DRB1*16:01 (OR = 8.16, Pv < .001) was significantly higher in BD patients compared with healthy controls, whereas the frequency of the HLA-DRB1*01:01 (OR = 0.03, Pv < .001) was significantly lower in BD patients. The most frequent extended haplotypes in our patients were HLA-A*02:01-B*55:01-DRB1*04:03.

Conclusion: This study is the first study evaluating an association between the HLA pattern and BD in the patients with BD from North West and North Iran.
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http://dx.doi.org/10.1002/iid3.325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416031PMC
September 2020

IL-27 and autoimmune rheumatologic diseases: The good, the bad, and the ugly.

Int Immunopharmacol 2020 Jul 29;84:106538. Epub 2020 Apr 29.

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

The footprint of cytokines is evident in almost every biological process, such as development, as well as the pathogenesis of the different diseases, immune responses to pathogens, etc. These small proteins are categorized into different functional classes; for instance, they can play a pro-inflammatory or anti-inflammatory role in different situations, or they can confer a polarization to the immune system. Interleukin (IL)-27 is a member of the IL-12 family. Antigen-presenting cells are the primary source of IL-27 production, which exerts its effects by bindings to the IL-27 receptor expressed on the surface of target cells. Interaction of IL-27 and IL-27 receptor leads to activation of the JAK-STAT and p38 MAPK signaling pathways. Most studies focused on the inflammatory effects of this cytokine, but gradually anti-inflammatory effects were also revealed for this cytokine, which changed the traditional perception of the function of this cytokine. The functionality of IL-27 in the pathogenesis of rheumatic diseases has been attributed to a double-blade sword. Hence, novel therapeutic approaches have been devised targeting IL-12 family that has been accompanied with promising results. In this review, we focused on the inflammatory and anti-inflammatory properties of IL-27 in different autoimmune rheumatologic diseases and its plausible therapeutic potentials.
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http://dx.doi.org/10.1016/j.intimp.2020.106538DOI Listing
July 2020

Dynamic variation of kidney injury molecule-1 mRNA and protein expression in blood and urine of renal transplant recipients: a cohort study.

Clin Exp Nephrol 2019 Oct 13;23(10):1235-1249. Epub 2019 Jul 13.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Building No. 7, Poursina Ave, Tehran, Iran.

Background: Acute renal dysfunction still constitutes a highly significant obstacle to renal transplantation outcome. Kidney injury molecule-1 is highly upregulated in proximal tubular cells and shed into the urine and blood circulation following kidney injury. The aim of current cohort study was to evaluate the urine KIM-1 (uKIM-1) mRNA expression level and its protein concentration in blood and urine samples to determine whether sequential monitoring of KIM-1 in renal allograft recipients is a reliable biomarker for predicting the clinical status and outcome.

Methods: Both uKIM-1 mRNA expression level and the level of serum and uKIM-1 protein concentration in the 52 renal transplant recipients were respectively quantified using real-time PCR and ELISA methods at 2, 90 and 180 days after transplantation.

Result: KIM-1 mRNA and protein expression level in the blood and urine samples of patients with graft dysfunction was significantly higher than patients with well-functioning graft on days 2, 90 and 180 after transplantation. Receiver-operating characteristic curve analysis of mRNA and protein expression levels showed that urinary and blood KIM-1 at months 3 and 6 could predict acute renal dysfunction at 6 months and 1 year after transplantation.

Conclusion: Sequential monitoring of uKIM-1 mRNA expression level and its protein concentration in the serum and urine samples of renal transplant patients suggests that KIM-1 could be a sensitive and specific biomarker for early diagnosis and prognosis of kidney allograft injury.
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http://dx.doi.org/10.1007/s10157-019-01765-yDOI Listing
October 2019

TLR-2, TLR-4 and MyD88 genes expression in renal transplant acute and chronic rejections.

Int J Immunogenet 2019 Dec 9;46(6):427-436. Epub 2019 Jul 9.

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

Background: Graft rejection due to alloreactivity is still the main obstacle to successful renal transplantation. Toll-like receptors (TLRs), which are significantly involved in initiating inflammation, triggering innate immunity, occurrence of ischaemia reperfusion injury (IRI) and subsequent deterioration of allograft function, are of interest in molecular diagnosis of graft rejection.

Methods: In present research, we have evaluated the mRNA expressions of TLR-4, TLR-2 and myeloid differentiation primary response gene 88 (MyD88) in peripheral blood mononuclear cells (PBMCs) and biopsy samples of 26 stable graft function (SGF), 14 acute T-cell-mediated rejection (ACMR), six acute antibody-mediated rejection (AAMR), 10 chronic T-cell-mediated rejection (CCMR) and four chronic antibody-mediated rejection (CAMR) cases of renal transplant recipients, using TaqMan detector real-time polymerase chain reaction (RT-PCR).

Results: It was found that TLR4 mRNA level was significantly elevated in PBMCs of both ACMR (P.v: 0.025) and CCMR (P.v: 0.007) cases, while TLR2 gene was upregulated only in PBMCs of ACMR (P.v: 0.024). Moreover, MyD88 expression was increased in biopsy samples of all rejection groups AAMR (P.v: 0.032), ACMR (P.v: 0.002), CAMR (P.v: 0.038) and CCMR (P.v: 0.013) and could distinguish them from stable grafts with AUC (area under curve) of 0.81, 0.80, 0.83 and 0.77, respectively.

Conclusion: These data showed that MyD88 gene upregulation in renal tissue could have diagnostic value and increased level of TLR4 mRNA in PBMCs could be suggestive of cell-mediated rejections. Therefore, monitoring the expression level of inflammatory signalling genes might be useful in predicting allograft rejection.
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http://dx.doi.org/10.1111/iji.12446DOI Listing
December 2019

TIM family gene polymorphism and susceptibility to rheumatoid arthritis: Systematic review and meta-analysis.

PLoS One 2019 7;14(2):e0211146. Epub 2019 Feb 7.

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

Background: TIM-family proteins are expressed on different immune cells such as dendritic cells, macrophages, type 1 and 2 T helper (Th) cells. Therefore, they have the ability to contribute to the various intracellular signals and immune responses, importantly the regulation of Th1 and Th17 cell differentiation, which plays a remarked role in fight against inflammatory and autoimmune diseases. Association of TIM family gene polymorphisms with rheumatoid arthritis (RA) has been frequently investigated. The findings however are not entirely consistent. Therefore, we carried out the present meta-analysis to examine the association between RA and the following TIM family gene polymorphisms: rs41297579, rs1036199, rs10515746, and rs7700944.

Methods: A systematic search of Scopus, PubMed, and Web of Science databases was conducted through December 2018. Combined odds ratios (OR) with their corresponding 95% confidence intervals (CI) were calculated under different possible genetic models.

Results: A total of eight case-control studies were included in the present meta-analysis. The results demonstrated significant association of RA with TIM-3 rs1036199 polymorphism under dominant (OR, 1.93, 95% CI, 1.43-2.61) and allelic models (OR, 1.74, 95% CI, 1.31-2.30). None of the other examined polymorphisms indicated significant association with RA.

Conclusions: The present meta-analysis revealed that the TIM-3 rs1036199 polymorphism might confer susceptibility to RA. Further studies are required to reassert our findings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211146PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366744PMC
November 2019

Sequential monitoring of TIM-3 mRNA expression in blood and urine samples of renal transplant recipients.

Transpl Immunol 2019 06 3;54:9-16. Epub 2018 Nov 3.

Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: T cell immunoglobulin and mucin domain 3 (TIM-3), as a co-inhibitory receptor expressed on Th1, Th17, CD8T, FoxP3 + Treg and innate immune cells, plays an important role in suppression of T cell-mediated immune responses, tolerance induction and T cell exhaustion. In this study, we evaluated sequential alterations of TIM-3 mRNA expression level in blood and urine samples of renal transplant recipients to predict approaching clinical episodes.

Methods: A total of 52 adult renal transplant recipients (31 male and 21 female) were enrolled in this study. All the patients received kidney transplant from living unrelated donors. TIM-3 mRNA expression in peripheral blood mononuclear cells (PBMCs) and urinary cells were quantified using Real Time TaqMan polymerase chain reaction (PCR) at 4 different time points (pre-transplantation, 2, 90 and 180 days post-transplantation).

Result: TIM-3 mRNA expression level on days 2, 90 and 180 after transplantation was significantly higher in blood and urine samples of patients with graft dysfunction (GD) compared with patients with well-functioning graft (WFG). Our results also showed a high correlation between blood and urinary level of TIM-3 mRNA expression. The data from Receiver Operating Characteristic (ROC) Curve Analysis showed that blood and urinary TIM-3 mRNA expression level at month 3 and 6 could discriminate graft dysfunction (GD) from well-functioning graft (WFG) with high specificity and sensitivity.

Conclusion: Our data suggested that serial monitoring of TIM-3 mRNA level in the blood and urine samples of renal transplant recipients could be a useful non-invasive biomarker for prediction and diagnosis of allograft dysfunction.
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http://dx.doi.org/10.1016/j.trim.2018.10.007DOI Listing
June 2019

Antiapoptotic Molecule Survivin in Transplantation: Helpful or Harmful?

J Transplant 2018 1;2018:6492034. Epub 2018 Oct 1.

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

Survivin, an antiapoptotic molecule from inhibitor of apoptosis protein (IAP) family, is most known for its implication in cancer as there are some efforts to apply it for diagnostic as well as therapeutic purposes in oncology. On the other hand, it could be a useful molecule to be positively targeted when trying to save tissue and promote cells viability. Since protecting the allograft from ischemia reperfusion injury and inflammation-induced damage is a considerable objective in transplantation, it is reasonable to take advantage from antiapoptotic agents like survivin in order to achieve this goal. However, survivin's potential ability to induce malignancies makes some concerns about its use in clinic. The other barrier is this molecule's involvement in lymphocytes development and proliferation which might increase the risk of graft rejection due to adaptive immune system overactivation. In this review we summarize the few studies carried out about survivin's effect on graft survival and probable advantages and disadvantages of its overexpression in transplantation.
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http://dx.doi.org/10.1155/2018/6492034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188762PMC
October 2018

Interferon regulatory factors: Where to stand in transplantation.

Transpl Immunol 2018 12 16;51:76-80. Epub 2018 Oct 16.

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

Interferon regulatory factors (IRFs) are implicated in regulating inflammatory responses to pathogens and alloantigens. Since transplantation is usually accompanied by ischemia reperfusion injury (IRI), acute and chronic rejections, as well as immunodeficiency due to immunosuppressive drugs, IRFs seem to play a considerable role in allograft outcome. For instance, IRF-1 has been shown to be involved in pathogenesis of IRI; however, IRF-2 exhibits an opposite function. Some IRF-3 and 5 SNPs are associated with better or worse graft survival rates. Of note, IRF-4 inhibition has resulted in improved transplant outcomes. Herein we review available studies about IRFs influence on various stages of transplantation.
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http://dx.doi.org/10.1016/j.trim.2018.10.001DOI Listing
December 2018

Toll-Like Receptor 4 in Renal Transplant.

Exp Clin Transplant 2018 06;16(3):245-252

>From the Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Toll-like receptor 4 is a member of the cell surface pattern recognition receptors involved in pathogenesis of several infectious and autoimmune diseases. The wide range of Toll-like receptor 4 extrinsic and intrinsic ligands means that it has considerable ability to trigger infectious and sterile inflammation, the latter assumed to be the principal cause of ischemia-reperfusion injury. With the rising number of renal transplant procedures using deceased donors, in addition to prolonged ischemia time due to organ transport and consequently increased risk of ischemia-induced injuries, the prevention of detrimental immune responses and/or overcoming these after they initiate could be beneficial for graft survival. This review aims to summarize past and present studies conducted about the role of Toll-like receptor 4 in early and late phases of transplant, including gene expression and polymorphism evaluations.
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June 2018

High Expression of FOXP3 mRNA in Blood and Urine as a Predictive Marker in Kidney Transplantation.

Prog Transplant 2018 06;28(2):134-141

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

Background: Diagnosis of allograft dysfunction by noninvasive biomarker tests is preferable to invasive allograft biopsies and has been extensively considered in recent years. This study aims to evaluate blood and urinary forkhead box P3 (FOXP3) messenger RNA (mRNA) expression in renal transplant recipients in an attempt to determine whether differential diagnosis of graft dysfunction is feasible using mRNA profiles.

Methods: We analyzed FOXP3 mRNA expression in paired urinary and peripheral blood mononuclear cell (PBMC) samples. A total of 91 kidney transplant recipients enrolled in this study that were classified into 3 groups: biopsy-proven acute rejection (AR; n = 27), chronic allograft nephropathy (n = 19), and well-functioning graft (n = 45). The FOXP3 mRNA expression was quantified by TaqMan probe real-time polymerase chain reaction.

Results: Acute rejection patients had a higher expression level of transcription factor FOXP3 compared to the chronic nephropathy and control groups. Analysis of receiver operating characteristic curves showed that rejection could be diagnosed with 100% sensitivity and 96% specificity in urine, and 92% sensitivity and 86% specificity in PBMC samples using the optimal FOXP3 mRNA cutoff value. We subdivided the AR group into progressive and nonprogressive patients, which showed a significant difference in FOXP3 mRNA expression. This result confirmed the role of FOXP3 as a diagnostic marker in predicting transplantation outcomes.

Conclusion: Our results suggested that elevated expression of FOXP3 in blood and urine samples from kidney transplant recipients could be a useful noninvasive biomarker to diagnose graft dysfunction.
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http://dx.doi.org/10.1177/1526924818765812DOI Listing
June 2018

Expression patterns of Toll like receptor (TLR)-2, TLR-4 and myeloid differentiation primary response gene 88 (MYD88) in renal transplant patients developing allograft dysfunction; a cohort study.

Transpl Immunol 2018 06 13;48:26-31. Epub 2018 Feb 13.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Molecular immunology research center, Tehran university of medical sciences, Tehran, Iran. Electronic address:

This cohort intends to determine the sequential dynamic changes in Toll-like receptor (TLR)-4, TLR-2, and myeloid differentiation primary response gene 88 (MYD88) mRNA expressions in PBMCs and biopsy samples from kidney allograft recipients in relation to graft function. This study enrolled 52 renal transplant patients, 27 with well functioning graft (WFG) and 25 graft dysfunction (GD). Peripheral blood samples pre- and post-transplantation (days 2, 90 and 180) were collected to analyze mRNA expression levels of TLR-2, TLR-4, and MYD88 genes in relation to allograft function during one-year follow up. The mean dynamic changes of post-transplant TLR-2, TLR-4, and MYD88 mRNA expressions were significantly higher in GD compared to WFG patients (P = .001). ROC curve analysis based on glomerular filtration rate (GFR) index showed the area under curve (AUC) values for the genes: TLR-2(0.89;P < .001), TLR-4(0.86;P < .001), and MYD88(0.75;P = .003) in the third month post-transplantation for GD diagnosis. The calculated AUCs for the expressions of genes in allograft biopsies were 0.94(TLR-2), 0.95(TLR-4), and 0.98(MYD88) in the sixth month post-transplant based on pathology report (P < .001). Our results indicate that sequential monitoring of the expression patterns of TLR-2, TLR-4, and MYD88 in PBMCs and biopsy samples could be considered as predictive biomarkers for early and late kidney allograft function.
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http://dx.doi.org/10.1016/j.trim.2018.02.005DOI Listing
June 2018

Enzyme-Linked Immunosorbent Spot (ELISpot) monitoring of cytokine-producing cells for the prediction of acute rejection in renal transplant patients.

Eur Cytokine Netw 2017 Sep;28(3):93-101

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

The purpose of this study was to evaluate T-cell immunity markers using serial post-transplantation monitoring of cytokine-producing cells during the first post-transplant months for the prediction of acute rejection and potentially chronic rejection of kidney allograft. We followed 57 kidney allograft recipients for meanly 3 years post-transplantation. Blood samples were collected pre-transplant, 2, 4 and 12 weeks post-transplant. The frequencies of IL-10-, IL-17- and IFN-γ-producing cells were determined in all time-points using ELISPOT assay. The results of ELISpot monitoring and levels of IL-23 and TGF-β were compared between recipients with acute (n = 12) or chronic rejection episodes and patients with stable graft function (n = 45). In all post-transplant time-points, significantly high frequencies of IFN-γ- and IL-17-producing cells and low frequency of IL-10-producing cells were observed in rejection group versus patients with stable graft function (P < 0.0001). The ROC curve analysis for determining the reliability of cytokine-producing cells for the prediction of acute rejection revealed that AUC was 0.046 for IL-10 (P < 0.001), 0.927 for IL-17 (P < 0.001) and 0.929 for INF-γ-producing cells (P < 0.001). Our results indicate that analyzing the frequencies of INF-γ/IL-10/IL-17-producing cells may define a reliable panel for the prediction of acute rejection within the first post-transplant year which could also be applicable for the prediction of chronic rejection episodes.
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http://dx.doi.org/10.1684/ecn.2017.0397DOI Listing
September 2017

Association of Human Leukocyte Antigens Class I and II with Graves' Disease in Iranian Population.

Iran J Immunol 2017 Sep;14(3):223-230

Department of Cellular and Molecular Biology, Kish International Campus, University of Tehran, Kish Island, Iran.

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.
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http://dx.doi.org/IJIv14i3A5DOI Listing
September 2017

High expression of TIM-3 and KIM-1 in blood and urine of renal allograft rejection patients.

Transpl Immunol 2017 08 27;43-44:11-20. Epub 2017 Jul 27.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: T cell immunoglobulin and mucin domain 3 (TIM-3) is involved in alloimmune and autoimmune responses, as well as tolerance induction in kidney transplantation. Kidney injury molecule-1 (KIM-1) is highly expressed in epithelial cells of the injured proximal tubule. In this study, we have investigated both urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins in renal allograft recipients diagnosed with acute allograft rejection (AR) and chronic allograft dysfunction (CAD), as well as those with well-functioning transplants (WFG).

Methods: We divided 85 patients into the following groups: AR (n=24), CAD (n=19), and WFG (n=42). TIM-3 and KIM-1 mRNA expressions were quantified using real-time reverse-transcription TaqMan probe polymerase chain reaction (RT-PCR). An ELISA test was used to measure the amount of KIM-1 protein in serum and urine samples.

Results: AR and CAD patients had significantly greater urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins compared to WFG patients. Receiver operating characteristic (ROC) analysis showed that these molecules discriminated Allograft rejections from WFG.

Conclusion: Quantification of TIM-3 and KIM-1 mRNA expressions, along with KIM-1 protein measurements in urine and blood could be employed as promising tools for noninvasive diagnosis of allograft dysfunction.
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http://dx.doi.org/10.1016/j.trim.2017.07.002DOI Listing
August 2017

Human Leukocyte Antigen (HLA) Class I and II Polymorphism in Iranian Healthy Population from Yazd Province.

Iran J Allergy Asthma Immunol 2017 Feb;16(1):1-13

Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Immunogenetic Laboratory, Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

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%), HLA-DRB* 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%), HLA-A*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.
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February 2017

Association Between TLR2, TLR4, and CD14 Gene Polymorphisms and Acute Rejection in Kidney Transplant.

Exp Clin Transplant 2018 02 14;16(1):31-37. Epub 2017 Apr 14.

Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: Toll-like receptors play an important role in innate and adaptive immune responses and can induce acute graft rejection, especially in the early phase after transplant. The aim of this study was to evaluate the possible association between TLR2, TLR4, and CD14 polymorphisms and acute renal rejection.

Materials And Methods: Our study included 239 patients seen between 2013 and 2015. Patients were classified into 3 groups: acute rejection group (71 patients), stable graft function group (71 patients), and healthy control group (97 patients). Polymorphisms in TLR2 (Arg753Gln, rs5743708), TLR4 (Asp299Gly, rs4986790; Thr399Ile, rs4986791), and CD14 (-159C/T, rs2569190) were determined by the TaqMan allelic discrimination assay for detection of single-nucleotide polymorphisms.

Results: The genotype distribution of CD14 rs2569190C/T was found to be significantly different among the acute rejection, stable graft function, and healthy control groups (P < .05). Interestingly, based on logistic regression, CD14 genotype (rs2569190) in patients with acute rejection was still significant after including risk factors. The adjusted odds ratio for CD14 CT+TT over CC genotype was calculated as 3.172 (95% confidence interval, 1.397-7.200; P = .006). Moreover, incidence of acute rejection and graft loss were significantly more frequent in recipients carrying CD14 TT (95% confidence interval, 2.81-27.16; P ≤ .001). In contrast to CD14, no significant differences were observed in the single-nucleotide polymorphisms of TLR2 and TLR4 genes in the acute rejection group versus the stable graft function and healthy control groups. The presence of CD14 T allele was associated with a significantly lower rejection-free survival compared with the CD14 CT and CC genotypes (P ≤ .001).

Conclusions: Renal transplant recipients carrying the CD14-159 TT genotype have significantly higher risk of acute rejection and reduced transplant survival rate than patients with heterozygous or wild-type genotypes.
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http://dx.doi.org/10.6002/ect.2016.0115DOI Listing
February 2018

Comparative study of substance P and neurokinin A in gingival crevicular fluid of healthy and painful carious permanent teeth.

Dent Res J (Isfahan) 2017 Jan-Feb;14(1):57-61

Department of Pediatric Dentistry, Tehran University of Medical Sciences, Tehran, Iran.

Background: It is shown that neuropeptides can be transported from pulp chamber to periodontal ligament through apical foramen and accessory canals. Therefore, clinical pulpal pain leads to expression of preinflammatory neuropeptides such as substance (SP) and neurokinin A (NKA) in gingival crevicular fluid (GCF). This study aimed to evaluate levels of SP and NKA in GCF of carious and healthy permanent teeth, comparatively.

Materials And Methods: This cross-sectional study was performed on twenty children referred to Department of Pediatric Dentistry, Tehran University of Medical Sciences, who had a painful permanent first molar. Sampling was done by sterile paper cone from GCF of the mentioned teeth and the intact tooth of the other side of the jaw in the same patient. Values of SP and NKA were measured by ELISA test.

Results: The mean concentration of SP in GCF of painful carious and healthy teeth was 2.65 ± 0.56 and 1.83 ± 0.65 pcgr/ml, respectively. This value was 2.29 ± 0.29 and 1.61 ± 0.35 pcgr/ml for NKA concentration in carious and healthy teeth as well.

Conclusion: Significant higher levels of both SP and NKA in GCF of painful carious teeth were observed, which is in line with previous studies' findings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356390PMC
http://dx.doi.org/10.4103/1735-3327.201140DOI Listing
March 2017

Increased Expression of Toll-Like Receptors 2 and 4 in Renal Transplant Recipients that Develop Allograft Dysfunction: A Cohort Study.

Iran J Immunol 2017 Mar;14(1):24-34

Department of Immunology, School of Medicine, Ilam University of medical Sciences, Ilam, Iran.

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.
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http://dx.doi.org/IJIv14i1A3DOI Listing
March 2017

Effect of TNF-α Blockade in Gingival Crevicular Fluid on Periodontal Condition of Patients with Rheumatoid Arthritis.

Iran J Immunol 2016 Sep;13(3):197-203

Department of Periodontology, School of Dentistry, Tehran University of Medical Science, Tehran, Iran.

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.
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http://dx.doi.org/IJIv13i3A5DOI Listing
September 2016

Increased levels of CD4(+) and CD8(+) T cells expressing CCR1 in patients developing allograft dysfunction; a cohort study.

Transpl Immunol 2016 09 24;38:67-74. Epub 2016 May 24.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Leukocyte infiltration into the graft has pivotal effects on kidney transplantation outcome. The present study sought to determine whether the expression of sequential chemokine receptors on CD4(+) and CD8(+) T cells in human renal allograft can predict clinical episodes.

Methods: Blood samples from 52 consecutive renal transplant patients were evaluated at the time of transplantation and at three times (2, 90 and 180days) after transplantation to analyze the expression of CCR1 and CXCR3 on CD4(+) and CD8(+) T cells by flowcytometry. A total of 30 biopsies, including protocol biopsy (n=24) and cause biopsy (n=6), were investigated according to the Banff criteria.

Results: The mean percentage of CD4(+) and CD8(+) T cells expressing CCR1 was significantly increased in patients with allograft dysfunction (n=25) (p=0.006, p=0.004). The mean fluorescence intensity of CXCR3 on CD4(+) and CD8(+) T cells were found to be significantly higher in graft dysfunction than that in well-functioning grafts. (p<0.001, p=0.007). Receiver Operating Characteristic (ROC) Curve Analysis showed that the calculated AUC was 0.86 at the third month for CD4(+)CCR1(+) and CD8(+)CCR1(+) (p<0.001). Multiple logistic regression analysis showed that an increase in CD4(+) expressing CXCR3 leads to a lower risk of graft dysfunction (OR=0.37), while an increase in CD8(+) expressing CCR1 results in a higher risk of graft dysfunction (OR=3.66).

Conclusion: During renal transplantation, CD4(+) and CD8(+) T cells expressing CCR1 were increased in patients who developed graft dysfunction. These findings may prospectively predict allograft dysfunction, and help elucidate the underlying pathogenic mechanisms.
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http://dx.doi.org/10.1016/j.trim.2016.05.003DOI Listing
September 2016

Altered Expression of MicroRNAs Following Chronic Allograft Dysfunction with Interstitial Fibrosis and Tubular Atrophy.

Iran J Allergy Asthma Immunol 2015 Dec;14(6):615-23

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

Chronic allograft dysfunction (CAD) remains the major cause of renal transplant loss and characterized by interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs (miRNAs) are implicated in many biological processes as well as innate and adaptive immune responses. We aimed to investigate whether CAD with IFTA is associated with differential expression of miR-142-5p, miR-142-3p and miR-211 within biopsy and peripheral blood mononuclear cell (PBMC) samples and whether expression of miRNAs are diagnostic for CAD with IFTA and predicts renal allograft function. In this study, biopsy and PBMC samples of 16 CAD with IFTA and 17 normal allografts (NA) were collected. Using Taqman MicroRNA Assays the expression levels of miR-142-5p, miR-142-3p and miR-211 were determined in two groups. Our results showed that miR-142-5p and miR-142-3p were significantly (p<0.0001) up-regulated and miR-211 was significantly (p<0.0001) down-regulated in renal allograft tissues of CAD with IFTA compared with NA recipients. Moreover, miR-142-3p and miR-211 were significantly (p<0.0001) up-regulated and down-regulated respectively in PBMC samples of CAD with IFTA. According to the ROC curve analysis, miR-142-5p in biopsy samples, but miR-142-3p and miR-211 both in biopsy and PBMC samples could be used as a diagnostic biomarker of CAD with IFTA and a prediction factor of allograft function. In this study, miRNAs were differentially expressed in the kidney allograft biopsy and simultaneously in PBMC samples of patients with CAD with IFTA. We suggest that the expression of miRNAs in PBMC might be used for monitoring the post transplantation and also as potential non-invasive biomarkers of kidney graft function and CAD with IFTA.
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December 2015

Association of HLA class II (DRB1, DQA1, DQB1) alleles and haplotypes with myasthenia gravis and its subgroups in the Iranian population.

J Neurol Sci 2015 Dec 12;359(1-2):335-42. Epub 2015 Nov 12.

Iranian Center for Neurological Research, Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Heterogenic pattern of HLA associations with myasthenia gravis (MG) among different ethnicities and also among different MG subgroups has been the subject of debate in large series of many studies. One hundred and sixty Iranian MG patients were investigated for HLA class II (DRB1, DQA1, DQB1) associations compared to two hundred healthy controls from the same ethnic population. DRB1*11 DQA1*0501 DQB1*0301 haplotype was found to be protective for total (ocular plus generalized) MG (Pc=0.005, OR=0.49) and generalized MG (Pc=0.008, OR=0.49). DRB1*04 DQA1*0301 DQB1*0302 haplotype (Pc=0.03, OR=2.25) was predisposing for anti-acetylcholine receptor (AChR) antibody-positive MG, while DRB1*16 DQA1*0102 DQB1*05 (Pc=0.013, OR=4.28) was predisposing for anti-muscle specific tyrosine kinase (MuSK) antibody-positive MG. There was also a trend of positive association for DRB1*14 DQA1*0104 DQB1*05 haplotype with MuSK-positive MG (Pc=0.054, OR=3.97). Among other MG subgroups and with less significance, DRB1*0101 DQA1*0101 DQB1*05 haplotype (P=0.016, OR=3.68) had positive association with pure ocular MG, and DRB1*03 DQA1*0501 DQB1*0201 haplotype (P=0.024) had negative association with thymomatous MG. This study highlights the importance of appropriate MG subgrouping according to clinical and paraclinical characteristics in HLA studies among MG patients.
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http://dx.doi.org/10.1016/j.jns.2015.11.021DOI Listing
December 2015

Differential expression of microRNAs in renal transplant patients with acute T-cell mediated rejection.

Transpl Immunol 2015 Sep 20;33(1):1-6. Epub 2015 May 20.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: MicroRNAs (miRNAs) regulate most of encoding genes and protein. In this study, we aimed to investigate the expression levels of miR-142-5p, miR-142-3p, miR-155 and miR-223 in paired biopsy and peripheral blood mononuclear cell (PBMC) samples of renal allograft recipients with acute T-cell mediated rejection (ATCMR), compared with normal allografts (NA).

Methods: In this study, the expression levels of individual miRNAs were determined in biopsy and PBMC samples of 17 recipients with ATCMR and 18 recipients with NA.

Results: Our results showed that the intragraft expression levels of all studied miRNAs were significantly higher in ATCMR than NA. However, regarding the PBMC samples, miR-142-3p and miR-223 were significantly increased in ATCMR than NA. Receiver operating characteristic (ROC) analysis showed that miR-142-5p, miR-142-3p, miR-155 and miR-223 in biopsy samples and miR-142-3p and miR-223 in PBMC samples could discriminate ATCMR from NA recipients.

Conclusion: It has been reported that high intragraft expressions of miRNAs have a profound role in the pathogenesis of ATCMR process. Our results showed that high expression of all the studied miRNAs in biopsies and miR-142-3p and miR-223 in PBMC samples could be used as suggestive diagnostic tools to discriminate ATCMR patients from NA.
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http://dx.doi.org/10.1016/j.trim.2015.05.002DOI Listing
September 2015

Association of HLA class II alleles with hepatitis C virus clearance and persistence in thalassemia patients from Iran.

J Med Virol 2015 Sep 12;87(9):1565-72. Epub 2015 May 12.

Department of Nanomedicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

There is no published data on association of HLA class II alleles with clearance or persistence after acute hepatitis C virus (HCV) infection in patients from Iran. HLA DRB1, DQA1, and DQB1 alleles were determined using polymerase chain reaction amplification with sequence specific primers (PCR-SSP) on a total of 117 thalassemia patients (63 with chronic infection, and 54 with viral clearance) and 120 healthy controls. HLA-DRB1*0301 and DQA1*0501 alleles were found significantly present in patients with HCV clearance compared to those with chronic infection (P = 0.03 and P = 0.0007, respectively). By contrast, DRB1*0701, DQA1*0201, and DQB1*0602 alleles occurred significantly in those with chronic infection compared to those with viral clearance (P = 0.004, P = 0.007, and P = 0.02, respectively). As compared to the controls, DRB1*0301, DRB1*11, DQA1*0501, and DQB1*0301 alleles showed a significant decrease in chronic patients (P = 0.002, P = 0.001, P = 0.0001, and P = 0.0004, respectively). Furthermore, the haplotype frequencies of DRB1*0301, DQA1*0501, DQB1*0201, and DRB1*1101, DQA1*0501, DQB1*0301 were found significantly higher (P = 0.004 and P = 0.04, respectively) in patients with HCV clearance than those with chronic infection. By contrast, the haplotype DRB1*0701, DQA1*0201, DQB1*0201 occurred more frequently (P = 0.02) in those with chronic infection compared with those with viral clearance. These findings suggest that particular HLA alleles and related haplotypes may have an influence on the outcome of HCV infection among the Iranian patients. Some of the HLA alleles found in the Iranian patients are different from those reported elsewhere, suggesting that the immunogenetic makeup for HCV clearance or persistence may vary based on the ethnicity.
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http://dx.doi.org/10.1002/jmv.24211DOI Listing
September 2015
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