Samaneh Delavari; Mehri Ghafourian; Elham Rajaei; Karim Mowla; Ata Ghadiri
Abstract
Background: Rheumatoid arthritis (RA) is the most common rheumatoid disease of unknown etiology, determined by the articular cartilage destruction and bone loss. The hallmark of RA is the defect in immune tolerance. Regulatory T cells (Treg) play a critical role in the protection of peripheral tolerance. ...
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Background: Rheumatoid arthritis (RA) is the most common rheumatoid disease of unknown etiology, determined by the articular cartilage destruction and bone loss. The hallmark of RA is the defect in immune tolerance. Regulatory T cells (Treg) play a critical role in the protection of peripheral tolerance. Objective: To assess the percentage of CD4+/CD25+/high/CD127low/- Treg cells in peripheral blood of RA patients as compared with the healthy individuals. Methods: The number of CD4+/CD25+/high/CD127low/- Treg cells was assessed by multicolor flow cytometry. The clinical disease activity of RA patients was determined by disease activity score 28 (DAS-28). The correlations of DAS-28 and erythrocyte sedimentation rate (ESR) with Treg cells were evaluated. Results: The percentage of CD4+/CD25+/high/CD127low/- Treg cells in peripheral blood of RA patients significantly decreased as compared with the healthy individuals (P= 0.0002). The percentage of CD4+/CD25+/high/CD127low/- Treg cells negatively correlated with DAS-28 and ESR. Conclusion: This study concludes that the defect of Treg cells plays a vital role in the pathogenesis of this disease. Further studies are necessary to determine the role of Treg cells in the clinical course of rheumatoid arthritis.
Mehrnoosh Doroudchi; Abdolrasoul Talei; Helmout Modjtahedi; Alamtaj Samsami Dehaghani; Abdol Mohammad Pezeshki; Hilary Thomas; Abbas Ghaderi
Volume 2, Issue 4 , December 2005, , Pages 191-200
Abstract
Background: A soluble form of HER-2/neu extracellular domain (sHER-2) is reported to be released in the sera of metastatic breast cancer patients. Objective: To measure the level of sHER-2 in sera of 115 breast cancer patients. Methods: Serial samples of 27 patients with metastasis, 18 non-metastatic ...
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Background: A soluble form of HER-2/neu extracellular domain (sHER-2) is reported to be released in the sera of metastatic breast cancer patients. Objective: To measure the level of sHER-2 in sera of 115 breast cancer patients. Methods: Serial samples of 27 patients with metastasis, 18 non-metastatic patients, 15 patients in stage 0/I and 14 patients with accompanying benign breast disease were also included in this study. Results: No significant difference was observed between sHER- 2 level in the pre-operative sera of breast cancer patients and that of healthy individuals. Only 8 out of 27 patients whom later developed metastasis showed elevated levels of sHER-2 in their first serum sample. However, a trend of increase in the level of sHER-2 was observed in 14 (51.8%) of 27 metastatic sera before clinical diagnosis of the metastasis. A significant association between sHER-2 positive status and vascular invasion of the tumor was observed (P = 0.02). In addition, significant correlation of sHER-2 level with CEA (highest r = 0.74) and CA 15.3 (highest r = 0.74) tumor marker levels in the serial sera were observed. The mean time from sHER-2 positivity to tumor metastasis was calculated to be 98 days (range = 29-174). Conclusion: Our results indicate that a relatively high percentage of Iranian patients with breast cancer show an elevated level of sHER-2 in their sera before clinical diagnosis of the tumor metastasis. Therefore, measuring the level of this oncoprotein, not only helps physicians in monitoring the patients during HERCEPTINTM therapy, but also can be helpful in choosing more aggressive treatments at the early satges of tumor metastasis.
Monireh Zare; Behnaz Valipour; Seyede Momeneh Mohammadi; Mohammad Nouri; Aliakbar Movassaghpour; Hojjatollah Nozad Charoudeh
Volume 14, Issue 3 , September 2017, , Pages 192-199
Abstract
Background: The mammalian target of rapamycin (mTOR) is important in hematopoiesis. Despite the central role of mTOR in regulating the differentiation of immune cells, the effect of mTOR function on cord blood mononuclear cells is yet to be defined. Objectives: To evaluate the effect of mTOR inhibition, ...
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Background: The mammalian target of rapamycin (mTOR) is important in hematopoiesis. Despite the central role of mTOR in regulating the differentiation of immune cells, the effect of mTOR function on cord blood mononuclear cells is yet to be defined. Objectives: To evaluate the effect of mTOR inhibition, using rapamycin on the proliferation and apoptosis of cord blood mononuclear cells, as well as on the B and T cell expansion. Methods: Cord blood mononuclear cells were cultured in the presence of IL-2, IL-7 and IL-15 cytokines and inhibited by rapamycin for 14 days. The harvested cells were evaluated at distinct time points by flow cytometry. Results: The mTOR expression decreased in the presence of rapamycin on day 14. Inhibition of mTOR reduced the proliferation of the cord blood mononuclear cells, yet did not influence apoptosis. Moreover, the number of T and NK cells was significantly reduced in the presence of rapamycin, while no change was observed in the B cell expansion. Conclusion: mTOR signaling plays a crucial part in cord blood derived NK and T cells expansion.
Eisa Salehi; Mohammad Vodjgani; Ahmad massoud; Abdolhosein Keyhani; Asadollah Rajab; Behrooz Shafaghi; Zahra Gheflati; Tahereh Aboufazeli
Volume 4, Issue 4 , December 2007, , Pages 197-205
Abstract
Background: Type-I diabetes is an autoimmune inflammatory disease in which pancreatic ß-cells are selectively destroyed by infiltrating cells. TNF-related apoptosis-inducing ligand (TRAIL) is a type-II membrane protein of the TNF superfamily which is expressed in different tissues, including pancreas ...
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Background: Type-I diabetes is an autoimmune inflammatory disease in which pancreatic ß-cells are selectively destroyed by infiltrating cells. TNF-related apoptosis-inducing ligand (TRAIL) is a type-II membrane protein of the TNF superfamily which is expressed in different tissues, including pancreas and lymphocytes. In humans, TRAIL interacts with four membrane receptors. TRAIL-R1 and TRAIL-R2 have cytoplasmic death domains, and can activate both caspases and NFκB pathways. The other two receptors, TRAIL-R3 and TRAIL-R4, are decoy receptors not capable of activating caspase cascade but may activate NF-κB and block apoptosis. As human beta cells are sensitive to TRAIL induced apoptosis, signaling via these molecules is considered to be a probable way of beta cell destruction. These molecules also are important in suppression of autorective T cells and immunoregulation. Objective: To explore the importance of TRAIL and its receptors at pathogenesis of type-I diabetes, we compared expression of these molecules on T-cells of diabetic patients and healthy controls. Methods: In this study, expression of TRAIL and its receptors at protein and mRNA levels were studied in freshly isolated peripheral T cells of 55 type I diabetic patients and 50 healthy individuals by flowcytometry, western blot and RT-PCR. Results: We found that expression of TRAIL and its receptors in peripheral T-cells at both protein and mRNA levels are significantly increased in patients (except for TRAIL-R2 mRNA which was slightly higher in controls) but increase in TRAIL, TRAIL-R3 (2.7% vs. >0.5%) and TRAIL-R4 (2.6% vs. >0.5%) is more considerable. sTRAIL in sera of patients was significantly lower than in controls (p=0.01). Conclusion: Our results explain resistance of autoreactive T-cells to immunoregulatory mechanisms. Besides, increased expression of TRAIL in autoreactive T-cells may play an important role in beta-cell destruction. Lower level of sTRAIL in diabetic patients may be a reason for hyperactivation of autoreactive T-cells.
Ahmad Karimi Rahjerdi; Mahyat Jafari; Mohammad Javad Motamedi; Jafar Amani; Ali Hatef Salmanian
Abstract
Background: Caused by bacterial, viral, and parasitic pathogens, diarrhea is the second leading cause of death among children under five. Two strains of E. coli, namely Enterotoxigenic, ETEC and Enterohemorrhagic EHEC are the most important causes of this disease in developing countries. EHEC is a major ...
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Background: Caused by bacterial, viral, and parasitic pathogens, diarrhea is the second leading cause of death among children under five. Two strains of E. coli, namely Enterotoxigenic, ETEC and Enterohemorrhagic EHEC are the most important causes of this disease in developing countries. EHEC is a major causative agent of bloody diarrhea and hemorrhagic uremic syndrome, while ETEC is the most important cause of diarrhea in neonates and travelers. Objective: To evaluate the immunologic properties of a subunit vaccine candidate comprising the main immunogenic epitopes from these two bacterial strains. Methods: The construct comprised of LTB and CfaB antigens from ETEC, and Intimin and Stx2B antigens from EHEC, was designed, analyzed and synthesized using bioinformatics methods. The chimeric gene was sub-cloned in the expression vector and expressed in E. coli host. The purified chimera protein was injected subcutaneously into the experimental animals. The production of specific antibodies was confirmed by immunological methods, and the protection capacity was evaluated by the challenge of immunized mice with the pathogenic bacteria. Results: Chimeric recombinant protein was able to increase IgG titer. Neutralization assay indicated that the antibodies generated against LtB moiety were able to neutralize ETEC toxin. In animal challenge study, all non-immune mice died within 3 days after the injection of toxin, but all immunized mice survived from Stx toxin. Conclusion: The immunity to both ETEC and EHEC bacteria is significant, and this structure can be considered as a candidate for vaccine production against these bacterial strains.
Samira Rajaei; Amir Hassan Zamani; Mahmood Jeddi-Tehrani; Maryam Tavakoli; Afsaneh Mohammadzadeh; Ali Dabbagh; Mahroo Mirahmadian
Volume 8, Issue 4 , December 2011, , Pages 201-208
Abstract
Background: Repeated Implantation Failure (RIF) is one of the most intricate obstacles in assisted reproduction. The cytokine and chemokine composition of uterine cavity seem to play important roles in the implantation process. Objective: To compare the cytokine profile in the endometrium of normal fertile ...
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Background: Repeated Implantation Failure (RIF) is one of the most intricate obstacles in assisted reproduction. The cytokine and chemokine composition of uterine cavity seem to play important roles in the implantation process. Objective: To compare the cytokine profile in the endometrium of normal fertile women and those with repeated implantation failure. Methods: After enzymatic digestion of endometrial tissues, whole endometrial cells and endometrial stromal cells from RIF and normal fertile women were cultivated and stimulated for cytokine secretion. The levels of IL-10, TGF-β, IFN-γ, IL-6, IL-8 and IL-17 in culture supernatants of the two groups were assayed by ELISA and compared together. Results: Endometrial stromal cells and whole endometrial cells of normal fertile women produced higher levels of IL-6, IL-8 and TGF-β compared to RIF group, although this difference was statistically significant only in endometrial stromal cells (p=0.005, 0.002 and 0.001, respectively). In addition, endometrial stromal cells of normal fertile women produced lower levels of IL-10 in comparison with RIF group (p=0.005). Conclusion: Disturbances in cytokine production at the feto-maternal interface could be a cause of implantation failure. A pro-inflammatory cytokine milieu seems to be pivotal for successful implantation.
Mir Davood Omrani; Mohammad Reza Mokhtari; Ali Tagizadae; Morteza Bagheri; Pedram Ahmad-Poor
Volume 5, Issue 4 , December 2008, , Pages 201-206
Abstract
Background: Despite advances in the medical care of renal transplant recipients which have led to an improvement in allograft survival, renal allograft rejection is still a major ob-stacle to successful organ transplantation. Understanding the mechanisms contributing to allograft rejection will be of ...
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Background: Despite advances in the medical care of renal transplant recipients which have led to an improvement in allograft survival, renal allograft rejection is still a major ob-stacle to successful organ transplantation. Understanding the mechanisms contributing to allograft rejection will be of great importance for the development of efficient antirejection strategies. Objective: The aim of current investigation was to study the impact of polymor-phisms of CCR5Δ32, CCR5- 59029 A/G and CCR2-V64I on renal allograft survival. Methods: Using PCR and PCR-RFLP methods in 84 renal transplant recipients, the influ-ence of CCR5Δ32, CCR5- 59029 A/G and CCR2-V64I polymorphisms on renal allograft survival in two rejector and non-rejector groups were examined. Rejector group was de-fined as having rejection before 1 year and non-rejector group had stable graft function at least for 5 years. Results: Significant reductions were found in the risk of renal transplant rejection in recipients possessing the CCR2-64I (A) allele (p=0.03) or 59029-A allele (p=0.03) compared to non-rejector group. There were no significant differences in the fre-quency of CCR5Δ32 polymorphism in rejector group compared to non-rejector group (p>0.05). Conclusion: It was possible to conclude that the chemokine receptors CCR2-V64I (A) and CCR5- 59029 A alleles may influence renal allograft survival.
Azam Torabi; Mojtaba Tahmoorespur; Fatemeh Vahedi; Nader Mosavari; Mohammadreza Nassiri
Volume 10, Issue 4 , December 2013, , Pages 205-215
Abstract
Background: Tuberculosis is a disease with high morbidity, caused mainly by Mycobaterium tuberculosis (M.tb.). DNA vaccines show a promising future due to their unique advantages over conventional methods. The early-secreted antigen target (ESAT)-6 and culture filtrate protein (CFP)-10 of M.tb. antigens ...
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Background: Tuberculosis is a disease with high morbidity, caused mainly by Mycobaterium tuberculosis (M.tb.). DNA vaccines show a promising future due to their unique advantages over conventional methods. The early-secreted antigen target (ESAT)-6 and culture filtrate protein (CFP)-10 of M.tb. antigens have been identified as vaccine candidates against Mycobacteria and used as subunit vaccines, DNA or protein, in different studies. Objective: To investigate the potential of pcDNA3.1+ plasmid containing CFP-10 and ESAT-6 genes in induction of local immune responses after intramuscular injection in BALB/c mice. Methods: pcDNA 3.1+ CFP-10 and pcDNA3.1+ ESAT-6 plasmids were prepared and defined groups of mice were injected intramuscularly with the plasmids both separately and in combination. The RNA was extracted from muscles after one month and cDNA was made using RT-PCR. The expressions of IL-4, IL-10 and IFN-γ genes cytokines were evaluated using comparative real time PCR. Results: Expression of IL-4 and IL-10 increased in the injection site of the mice groups which received plasmids encoding ESAT-6 and CFP-10 individually or together. More than 10-fold increase in IFN-γ expression was found in samples taken from mice groups inoculated by plasmids encoding ESAT-6 and CFP-10 individually or together. Conclusion: pcDNA 3.1+ESAT-6 and pcDNA3.1+CFP-10 plasmids can increase the expression of IFN-γ in mice after immunization.
Fatemeh Vahedi; Mahmoud Reza Jaafari; Mahmoud Mahmoudi
Volume 7, Issue 4 , December 2010, , Pages 210-216
Abstract
Background: DNA vaccines are third generation vaccines which have made promises to combat infectious diseases. Cationic liposomes are used as effective delivery systems for DNA vaccines to generate stronger immunity. Objective: Encapsulation of pcDNA3.1+PA plasmid, encoding protective antigen (PA) of ...
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Background: DNA vaccines are third generation vaccines which have made promises to combat infectious diseases. Cationic liposomes are used as effective delivery systems for DNA vaccines to generate stronger immunity. Objective: Encapsulation of pcDNA3.1+PA plasmid, encoding protective antigen (PA) of Bacillus anthracis (B. anthracis) into cationic liposomes, and evaluation of its effect on specific humoral specific immunity against PA were aimed. Methods: The liposomes containing pcDNA3.1+PA plasmids were prepared with phosphatidylcholine (PC), dioleoyl phosphatidylethanolamine (DOPE) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) using dehydration-rehydration method. BALB/c mice were immunized by intramuscular (IM) injection to investigate the immunogenicity of the formulations. The resulting specific antibodies against PA, total IgG, IgG1, IgG2a and IgG2b isotypes, were evaluated by enzyme linked immunosorbent assay (ELISA) method. Conclusion: A higher concentration of specific IgG against PA was found in sera of a group immunized with the encapsulated plasmid compared with the naked plasmid alone. This difference was significant for IgG1 isotype.
Nasrollah Erfani; Faezeh Moghaddasi-Sani; Mahboubeh Razmkhah; Mohammad Reza Haghshenas; Abdolrasoul Talaei; Abbas Ghaderi
Volume 9, Issue 4 , December 2012, , Pages 226-233
Abstract
Background: CCL22/MDC is a CC chemokine with a critical role in regulation of the immune balance in physiological condition. CCL22/CCR-4 ligation has been documented to participate in the migration of regulatory T (Treg) cells and Th2 lymphocytes to the site of breast tumors; circumstances that are known ...
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Background: CCL22/MDC is a CC chemokine with a critical role in regulation of the immune balance in physiological condition. CCL22/CCR-4 ligation has been documented to participate in the migration of regulatory T (Treg) cells and Th2 lymphocytes to the site of breast tumors; circumstances that are known to be associated with poor prognosis. Objective: To investigate the association of a single nucleotide polymorphism (SNP) in CCL22 gene; 16C/A (rs4359426; Asp2Ala), with susceptibility to breast cancer in a sample of Iranian population. Methods: 161 patients with pathologically confirmed breast carcinoma (mean age 49.3 ± 11.5 yrs) and 178 agematched healthy women (mean age: 49.3 ± 12.9 yrs) were studied. CCL22 genotypes were investigated by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Data was verified by direct automated sequencing. Arlequin analysis showed no deviation from Hardy-Weinberg equilibrium. Results: The most frequent genotype in both patient and control groups was wild type CC genotype with frequency of 146 out of 161 (90.7%) among patients and 153 out of 178 (86.0%) in control group (p=0.24). The frequency of CA genotype was 15 (9.3%) and 23 (12.9%) in patients and controls, respectively (p=0.38). No AA genotype was observed among patients but this genotype was observed with the frequency of 2 out of 178 (1.1%) in control subjects. The minor allele frequency (MAF) was 0.07 in the population. Conclusion: No correlation was found between the investigated genotypes and clinicopathological characteristics of the patients. Conclusively, results of this investigation do not support the association of 16C/A SNP (rs4359426; Asp2Ala) in CCL22 gene with susceptibility to, and progression of, breast cancer in Iranian population.
Feryal Dabagh-Gorjani; Fahimeh Anvari; Jaleh Zolghadri; Eskandar KamaliSarvestani; Behrouz Gharesi-Fard
Volume 11, Issue 4 , December 2014, , Pages 233-245
Abstract
Background: Preeclampsia (PE) is one of the most complex and life-threatening pregnancy disorders and is considered as a major cause of mortality among mothers and fetuses worldwide. Although the exact etiology of PE is not well known several lines of evidence support an immunological etiology for PE. ...
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Background: Preeclampsia (PE) is one of the most complex and life-threatening pregnancy disorders and is considered as a major cause of mortality among mothers and fetuses worldwide. Although the exact etiology of PE is not well known several lines of evidence support an immunological etiology for PE. Objective: To investigate the differences in the expression of TLRs 2, 4, 5, and 6 and a group of inflammatory cytokines including IL-1, IL-6, TNF-α and IFN-γ in placentas from PE and healthy pregnant women in their third trimester of pregnancy. Methods: This case-control study was performed on fifteen PE and fifteen age and gestational matched healthy pregnant women in the third trimester of pregnancy. Real time PCR (RT-PCR) technique was used to determine the expression of TLRs 2, 4, 5, and 6 in the maternal and fetal parts of the placenta. Moreover, the expressions of IL-1, IL-6, TNF-α and IFN-γ at RNA level in placental samples, peripheral, and cord blood were investigated. Results: The results of the present study indicated that the expressions of TLRs 4, 5 and 6 were significantly increased in both maternal part (p<0.001 and p<0.003 for TLRs 4, 6 and TLR 5, respectively) and fetal part (p<0.001), while TLR2 showed significant increase only in the fetal part of PE placentas (p<0.002). The levels of all studied cytokines showed over-expression within peripheral and cord blood samples from PE patients (p<0.001 for IL-1, IL-6, and IFN-γ and p<0.004 for TNF-α in both cord and peripheral blood samples). Conclusion: The finding of the present study indicated that the expression of the studied TLRs and inflammatory cytokines are generally suppressed in normal pregnancy, but are up regulated in preeclamptic women. Moreover, it seems that the maternal and fetal parts of the placenta may play different roles in the induction of the inflammatory status within the placenta.
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.
Mohammadreza Yazdani; Shahdad Khosropanah; Ahmad Hosseini; Mehrnoosh Doroudchi
Volume 13, Issue 4 , December 2016, , Pages 249-262
Abstract
Background: Atherosclerosis is a chronic inflammatory disease affecting large and
medium arteries. CD4+ T cells are known to play a role in the progression of the
disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role
in the disease and their reduction in acute coronary ...
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Background: Atherosclerosis is a chronic inflammatory disease affecting large and
medium arteries. CD4+ T cells are known to play a role in the progression of the
disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role
in the disease and their reduction in acute coronary syndrome is recently shown.
Objective: To investigate the frequency of nTreg subsets in the peripheral blood of
patients with atherosclerosis. Methods: Confirmation of atherosclerosis was done by
angiography and 15 ml heparinized blood was obtained from each of the 13 nondiabetic
patients and 13 non-diabetic, non-smoker individuals with normal/insignificant
coronary artery disease which was also confirmed by angiography. Lipid profiles of the
patients and controls were measured at the time of sampling. Mononuclear cells were
used for both RNA extraction and immunophenotyping by real-time PCR and
flowcytometry techniques, respectively. Results: In natural Treg subsets, the frequency
of CD4+CD45RO-CD25+Foxp3lo T-cells (resting nTregs) was greater in controls than
patients (p=0.02). The frequency of CD4+CD45RO+CD25hiFoxp3hi T-cells (activated
nTregs) was significantly higher in controls compared with patients (p=0.02). However,
the frequency of CD4+CD25+CD45RO+Foxp3- T-cells (effector/memory) increased in
patients compared with controls (p=0.01). Both the MFI and gene expression of Foxp3
were higher in control group than in patients (p=0.015 and p=0.017, respectively).
Moreover, the TGF-β gene expression showed a decrease in the peripheral blood
mononuclear cells of patients compared with controls (p=0.03). Conclusion: Decrease
in both subsets of resting and activated nTregs along with a decrease in the expression
of Foxp3 and TGF-β genes in patients with atherosclerosis suggests phenotypic changes
in these subsets, which may as well be correlated with a more inflammatory profile in
their lymphocytes.
Wei-Sung Li; Ching-Liang Chu; Mei-Hsing Chen; Yun-Sheng Lu; Jui-Sheng Lai; Bang-Jau You; Chi-Chien Lin
Aziz Mahmoudzadeh; Ali Akbar Pourfathollah; Mohammad Hossein Karimi; Seyed Mohammad Moazzeni
Volume 14, Issue 4 , December 2017, , Pages 270-280
Abstract
Background: Type-1 diabetes (T1D) is an autoimmune disease in which T lymphocytes destroy insulin-producing β-cells. Control of self-reactive T lymphocytes and recovery of diabetic injury is the end point of T1D. Objective: To investigate generation of tolerogenic dendritic cells (tolDCs) as an ...
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Background: Type-1 diabetes (T1D) is an autoimmune disease in which T lymphocytes destroy insulin-producing β-cells. Control of self-reactive T lymphocytes and recovery of diabetic injury is the end point of T1D. Objective: To investigate generation of tolerogenic dendritic cells (tolDCs) as an innovative method of diabetes therapy. Methods: Lentivirus vector production was achieved by GIPZ mouse CD40 shRNA, psPAX2 and pMD2G plasmids DNA. Purified bone marrow derived DCs were treated with CD40 shRNA, and expression of CD40 and mRNA level were evaluated by flow cytometry and Real-Time PCR, respectively. CD40 knock-down DCs were injected into STZ-induced diabetic mice. Blood glucose; glucose tolerance test and weight were analyzed in different groups. Results: Mice treated with CD40 shRNA transfected DCs showed considerable differences in blood glucose, glucose tolerance, and weight compared to other groups. Also cytokine assays indicated an increase in IL-13 production in the CD40 shRNA group. Conclusion: In streptozotocin-induced diabetic mice model, administration of tolerogenic dendritic cells could improve diabetic parameters.
Hong Ouyang; Jie Cheng; Jingdong Du; Huiyun Gan; Zheng Lu
Abstract
Background: T helper 17 (Th17) cells and the related cytokines, interleukin (IL)- 17 and IL-23, were proved to play pivotal roles during the development of allergic rhinitis (AR). IL-27, an anti-inflammatory cytokine, has been reported to promote the production of IL-12R and induce Th1 cell responses. ...
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Background: T helper 17 (Th17) cells and the related cytokines, interleukin (IL)- 17 and IL-23, were proved to play pivotal roles during the development of allergic rhinitis (AR). IL-27, an anti-inflammatory cytokine, has been reported to promote the production of IL-12R and induce Th1 cell responses. However, its effect on Th17 responses was not fully understood. Objective: We conducted the present research to explore the role of IL-27 in the regulation of Th17 responses in AR. Methods: Thirty confirmed AR patients and 20 controls were recruited for the study. The mRNA expression and protein levels of IL-27 were analyzed employing quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively, and their correlations with Th17 cytokines were analyzed. We utilized ELISA and qPCR to analyze the effect of IL-27 on the differentiation of Th17 cells and the production of IL-17 and IL-23 from peripheral blood mononuclear cells (PBMCs). Results: We found that the IL-27 levels in AR were downregulated and negatively related to IL-17 and IL-23 levels. The recombinant IL-27 inhibited the mRNA expression of RORγt and the protein expression of IL-17 and IL-23 in PBMCs through MEK, NF-κB, and JNK pathways. Conclusion: Our data demonstrated that IL-27 suppressed Th17 responses through MEK, NF-κB, and JNK pathways.
Yadan Wang; Xiaofei Wu; Yu Hu
Abstract
Background: Multiple myeloma (MM) is a malignant plasma cell proliferative disorder with limited immunotherapy treatment because of T cell dysfunction. Objective: To investigate the immunomodulatory function of bone marrow mesenchymal stromal cells (MM-BMSCs) on CD8+ T cells. Methods: Proliferation and ...
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Background: Multiple myeloma (MM) is a malignant plasma cell proliferative disorder with limited immunotherapy treatment because of T cell dysfunction. Objective: To investigate the immunomodulatory function of bone marrow mesenchymal stromal cells (MM-BMSCs) on CD8+ T cells. Methods: Proliferation and cytotoxicity were detected by cell counting kit-8 assay. Cell cycle was detected by flow cytometry, and p16 expression was detected by PCR. The expression of fibroblast activation protein α (FAPα) was evaluated by immunohistochemistry. Results: Co-culture of CD8+ T cells with MM-BMSCs decreased the cell survival rate and increased the killing rate (p=0.03, p=0.001, respectively), the percentage of cells in G0/G1 phase and p16 expression (p<0.001). FAPα was mainly in the mesenchymal matrix of the MM microenvironment and elevated in MM derived bone marrow compared to healthy donors (p<0.001). The FAPα inhibitor PT-100, increased survival and the killing rate (p<0.001, p=0.043, respectively), and decreased the percentage of cells in G0/G1 phase and p16 expression (p=0.024, p=0.004, respectively). Conclusion: Therefore, MM-BMSCs inhibit the proliferation and cytotoxicity of CD8+ T cells, significantly block the cell cycle and increase p16 expression in co-cultured CD8+ T cells in a cell-cell contact-dependent manner.
Maryam Nourizadeh; Elham Feizabadi; Milad Mirmoghtadaei; Ashraf Mohammadi; Mohammad Reza Fazlollahi; Leila Moradi; Zahra Pourpak
Abstract
Background: Few studies have evaluated COVID-19 vaccine efficacy in patients with inborn errors of immunity (IEI).Objective: To evaluate the levels of antibody (Ab) production and function after COVID-19 vaccination in IEI patients with phagocytic, complement, and Ab deficiencies and their comparison ...
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Background: Few studies have evaluated COVID-19 vaccine efficacy in patients with inborn errors of immunity (IEI).Objective: To evaluate the levels of antibody (Ab) production and function after COVID-19 vaccination in IEI patients with phagocytic, complement, and Ab deficiencies and their comparison with healthy controls.Methods: Serum samples were collected from 41 patients and 32 healthy controls at least one month after the second dose of vaccination, while clinical evaluations continued until the end of the third dose. Levels of specific anti-receptor-binding domain (RBD) IgG and anti-RBD neutralizing antibodies were measured using EUROIMMUN and ChemoBind kits, respectively. Conventional SARS-CoV-2 neutralization test (cVNT) was also performed. Cutoff values of ≤20, 20-80, and ≥80 (for cVNT and Chemobined) and 0.8-4.2, 4.2-8.5, and ≥8.5 (for EUROIMMUN) were defined as negative/weak, positive/moderate, and positive/significant, respectively.Results: A considerable distinction was observed between the Ab-deficient patients and the controls for Ab concentration (EUROIMMUN, p<0.01) and neutralization (ChemoBind, p<0.001). However, there was no significant difference compared with the other patient groups. A near-zero cVNT in Ab-deficient patients was found compared to the controls (p<0.01). A significant correlation between the two kits was found using the whole data (R2=0.82, p<0.0001).Conclusion: Despite varying degrees of Ab production, all Ab deficient patients, as well as almost half of those with complement and phagocytic defects, did not effectively neutralize the virus (cVNT). In light of the decreased production and efficiency of the vaccine, a revised immunization plan may be needed in IEI.
Abdollah Jafarzadeh; Mohammad Ali Sajjadi
Volume 3, Issue 1 , March 2006, , Pages 15-22
Abstract
Background: Helicobacter pylori infection is one of the most common gastrointestinal infections worldwide. Predominant T-helper 1 (Th1) responses with increased gamma interferon (IFN- γ) levels have been proposed to play an important role in H. pylori-induced peptic ulcer. However, bacterial factors ...
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Background: Helicobacter pylori infection is one of the most common gastrointestinal infections worldwide. Predominant T-helper 1 (Th1) responses with increased gamma interferon (IFN- γ) levels have been proposed to play an important role in H. pylori-induced peptic ulcer. However, bacterial factors contributing to the initiation of Th1 polarization of H. pylori-specific immune responses have not been characterized. Objective: Comparing serum concentrations of IL-18 in H. pylori-infected peptic ulcer (PU) patients, H. pylori-infected asymptomatic (AS) carriers and healthy control group and its association with bacterial virulence factor CagA. Methods: Thirty H. pylori-infected PU patients (20 patients were positive for anti-CagA antibody and 10 patients were negative for anti-CagA antibody), 30 H. pylori-infected (AS) carriers (15 subjects with positive test for anti-CagA antibody and 15 subjects with negative test for anti-CagA antibody) and 20 healthy uninfected subjects were included in this study. Serum concentration of IL-18 was measured by ELISA method. Results: The mean serum levels of IL-18 in PU patients (333.2 pg/ml ± 158), was significantly higher than those found in AS (146.5 pg/ml ± 90.1; P<0.001) and healthy control (82.2 pg/ml ± 45.7; P<0.0001). In both PU and AS groups, mean serum IL-18 levels in subjects with positive test for anti-CagA antibody were significantly higher than those observed in subjects with negative test for anti-CagA antibody. No significant difference was observed between serum IL-18 levels of healthy uninfected control and AS carriers with negative test for anti-CagA antibody. Conclusion: The results of the present study showed higher serum concentrations of IL-18 in peptic ulcer patients compared with H.Pylori carriers and healthy controls. This difference in cytokine levels may be explained by differential expression of H.Pylori CagA gene during the course of the infection.
Keyvan Ghasami; Fardin Faraji; Masoud Fazeli; Ali Ghazavi; Ghasem Mosayebi
Volume 13, Issue 1 , March 2016, , Pages 16-26
Abstract
Background: Statins, widely used cholesterol-lowering agents, have also been demonstrated to have anti-inflammatory and immunomdulatory effects. Objective: To evaluate the effects of atorvastatin in combination with Interferon-β in the treatment of multiple sclerosis (MS) in a randomized controlled ...
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Background: Statins, widely used cholesterol-lowering agents, have also been demonstrated to have anti-inflammatory and immunomdulatory effects. Objective: To evaluate the effects of atorvastatin in combination with Interferon-β in the treatment of multiple sclerosis (MS) in a randomized controlled clinical trial. Methods: Multiple sclerosis patients were randomized independently, in a double blind design, into one of two treatment groups. Control group (n=45) received 30 μg/week interferon β-1a via intra-muscular injection. Atorvastatin-treated group (n=50) received interferon β-1a similar to control group in addition to atorvastatin (40 mg/day) for 18-months. All clinical and immunological variables were measured at the baseline and at the end of the study. Results: There was no significant difference between the two groups in the expanded disability status scale scores and the number of gadolinium-enhancing lesions during the 18-month treatment period. After 18 months, the levels of interleukin (IL)-4, IL-10, transforming growth factor-β and serum ferric reducing antioxidant power in the atorvastatin treatment group were significantly higher than the control group. Levels of IL-17, TNF-α and lymphocyte proliferation in the atorvastatin treatment group were significantly lower than the control group. Conclusion: Although combined atorvastatin and interferon-β do not change the clinical course of MS, atorvastatin might have beneficial effects in MS treatment possibly through inducing anti-inflammatory responses.
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.
Mandana Sattari; Alireza Fathiyeh; Fatemeh Gholami; Hassan Darbandi Tamijani; Mahdi Ghatreh Samani
Volume 8, Issue 1 , March 2011, , Pages 20-26
Abstract
Background: Growth factors play a major part in wound healing in many tissues including the periodontium. Transforming growth factor-β1 (TGF-β1) is one of these factors present in the gingival crevicular fluid. In addition, it is considered as one of the most important anti-inflammatory cytokines. ...
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Background: Growth factors play a major part in wound healing in many tissues including the periodontium. Transforming growth factor-β1 (TGF-β1) is one of these factors present in the gingival crevicular fluid. In addition, it is considered as one of the most important anti-inflammatory cytokines. Interleukin-1β is a proinflammatory cytokine that presents itself in gingival inflammation and the GCF. Such factors might be of value as prognostic markers of wound healing activity and the therapeutic progress following flap surgery. Objective: The aim of this study was to evaluate the effect of surgical flap on the concentration of IL-1β and TGF-β in the GCF of patients with moderate to severe chronic periodontitis. Methods: The GCF samples were collected, using the Perio-Paper strip at phase 1 (pre-surgery), phase 2 (4th week post surgery) and phase 3 (12th week post surgery) from 20 sites of 10 patients undergoing flap surgery. After the elution, IL-1β and TGF-β concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results: The mean TGF-β and IL-1β concentration decreased from phase 1 to phase 3 (p<0.05). There were no significant statistical correlations between IL-1β and TGF-β1 concentrations in the 3 assessment phases. There was a significant statistical correlation between TGF-β1 concentrations and the Plaque Index (PI) in phase 2 (p<0.05). There was a significant statistical correlation (p<0.05) between IL-1β and TGF-β1 concentration and the probing pocket depth (PPD). Conclusion: The flap surgery has a significant effect on decreasing IL-1β concentration. In the case of TGF-β1, probably the decrease in the concentration after treatment might be due to the removal of the inflammatory stimulants.
Mahendra Narain Mishra; Puja Dudeja; Rakesh Kumar Gupta
Volume 11, Issue 1 , March 2014, , Pages 21-28
Abstract
Background: Pediatric bronchial asthma is associated with considerable morbidity. The study was carried out to examine the association of Human Leukocyte Antigen (HLA)- Class II with the disease as we found no similar study on Asian Indian population. Objective: To define the HLA-Class II antigens in ...
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Background: Pediatric bronchial asthma is associated with considerable morbidity. The study was carried out to examine the association of Human Leukocyte Antigen (HLA)- Class II with the disease as we found no similar study on Asian Indian population. Objective: To define the HLA-Class II antigens in Asian Indian pediatric patients with asthma. Methods: A total of 103 children with asthma and 152 controls were analysed for HLA Class II (DRB1, DQB1and DPB1) by PCR-SSP (Sequence Specific Primers) method. Total serum IgE levels were determined by ELISA assay. Results: A positive family history was recorded in 59 patients (57%) and 13 (8.5%) of healthy controls. Serum IgE levels were more than normal range in 72% of the patients and 33% of healthy subjects with mean values of 4877 and 627 IU/ml, respectively. DRB1*04 and DQB1*03 showed significant positive relations while DRB1*15 showed a negative association with asthma. DQB1*02 was more common in healthy individuals but was not statistically significant. Conclusions: A positive association of the DR4/DQB1*03 and a negative association of DRB1*15 was seen with extrinsic bronchial asthma. However, more studies are required on larger populations to confirm the association of HLA Class II alleles in Indians before a particular allele can be labeled as being protective or causative for asthma.
Maryam Hamidinia; Mehri Ghafourian Boroujernia; Abdolhassan Talaiezadeh; Ghasem Solgi; Maryam Taghdiri; Ali Khodadadi
Volume 10, Issue 1 , March 2013, , Pages 22-30
Abstract
Background: Regulatory T cells (T-regs) have an important role in cancer by suppression of protective antitumor immune responses. Regulatory T cells express the forkhead/winged helix transcription factor (FOXP3) and OX40 molecules which have important regulatory roles in the immune system. Objective: ...
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Background: Regulatory T cells (T-regs) have an important role in cancer by suppression of protective antitumor immune responses. Regulatory T cells express the forkhead/winged helix transcription factor (FOXP3) and OX40 molecules which have important regulatory roles in the immune system. Objective: To evaluate FOXP3 and OX40 transcripts in the peripheral blood mononuclear cells of women with breast cancer. Methods: Blood samples from 40 women with histologically-confirmed infiltrating ductal carcinoma of the breast and 40 healthy volunteer women without a history of malignancy or autoimmune disorders were collected. The abundance of FOXP3 and OX40 gene transcripts were determined by quantitative real-time PCR (qRT-PCR). Results: There was a significant positive correlation between FOXP3 and OX40 gene expression in women with breast cancer in a stage dependent manner. Conclusion: This finding emphasizes the importance of T-regs as predominant targets for breast cancer immunotherapy.
Masumeh Gorgian Mohammadi; Taravat Bamdad; Masoud Parsania; Hamid Reza Hashemi; Somayeh Puyanfard
Volume 6, Issue 1 , March 2009, , Pages 22-27
Abstract
Background: Herpes simplex virus type 1 is one of the most common viruses among human population. Studies demonstrate the essential role of cell mediated immunity, especially CD8+ T cells, in prevention and clearance of HSV1. Objective: It is of great importance to improve our knowledge about the kinetics ...
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Background: Herpes simplex virus type 1 is one of the most common viruses among human population. Studies demonstrate the essential role of cell mediated immunity, especially CD8+ T cells, in prevention and clearance of HSV1. Objective: It is of great importance to improve our knowledge about the kinetics of CTL responses to primary and secondary HSV-1 infection. Methods: Using a sensitive technique for detection and analysis of CD8+ T cells, granzyme B ELISA, the CTL activity in the spleens of Balb/c mice at various time points after intraperitoneal administration of HSV1 (strain KOS) in primary and secondary infections were determined. Results: During acute HSV-1 infection, virus specific cytotoxic T cells were detected at day 5 post virus inoculation and peaked at day 7. Six hours after secondary infection the activity of memory CD8+ T cells was detected and peaked at 12 hours post infection. Conclusion: The peak of CTL activity was found to be day 7 post infection in primary HSV-1 infections which decreased with time. In secondary infections, the activity of CTLs reached the highest level at 12 hours post infection.