Original Article
Hadi Reihani; Maryam Rastin; Mahmoud Mahmoudi; Mohsen Ghoryani; Nafiseh Abdollahi; Nafiseh Sadat Tabasi; Shahrzad Zamani Taghizadeh Rabe; Maryam Sahebari
Volume 12, Issue 2 , June 2015, Pages 82-93
Abstract
Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) ...
Read More
Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) has been considered as an immunomodulatory factor. Objective: To investigate the effect of 1,25VitD3 on Th17 cells and on the expression of related cytokines in SLE patients. Method: Thirty SLE patients (newly diagnosed or in remission) were sampled for 10 ml whole blood to isolate peripheral blood mononuclear cells (PBMCs) using Ficoll-Hypaque density gradient centrifugation. Isolated cells were cultured in the presence and absence of 50 nM 1,25VitD3. After incubation, cells were harvested and stimulated for 4-5 hours with phorbol myristate acetate (PMA) and ionomycin in the presence of brefeldin A. IL-17 secreting cells were analyzed by flowcytometry. RNA was extracted from cultured cells, cDNA was synthesized, and the expression levels of IL-6, IL-17, IL-23 and TGF- β genes were assessed by real-time PCR. Results: The percentage of Th17 cells (CD3+ CD8- IL-17+ T cells) decreased significantly in 1,25VitD3-treated cells (3.67 ± 2.43%) compared to untreated cells (4.65 ± 2.75%) ( p=0.003). The expression of TGF- β up regulated (1.38-fold) and the expression of IL-6 (50%), IL-17 (27%) and IL-23 (64%) down regulated after 1,25VitD3 treatment. Conclusion: This study showed that 1,25VitD3 modulates Th17 related pathways in SLE patients and revealed the immunomodulatory effect of 1,25VitD3 on the Th17 mediated autoimmunity.
Original Article
Eric Adua; Frank Oteng Danso; Oswald Mensah Boa-Amponsem; Frank Adusei-Mensah
Volume 12, Issue 2 , June 2015, Pages 94-103
Abstract
Background: During the initial phase of an infection, there is an upregulation of inducible nitric oxide synthase in the macrophages for the production of nitric oxide. This is followed by the recruitment of polymorphonuclear leukocytes (neutrophils) which release arginase. Arginase competes with inducible ...
Read More
Background: During the initial phase of an infection, there is an upregulation of inducible nitric oxide synthase in the macrophages for the production of nitric oxide. This is followed by the recruitment of polymorphonuclear leukocytes (neutrophils) which release arginase. Arginase competes with inducible nitric oxide synthase for a common substrate L-arginine. Objective: To investigate whether the entry of neutrophils and release of arginase can interfere with nitric oxide production from stimulated mouse macrophages. Methods: Neutrophils were isolated from human blood and stimulated with cytodex-3 beads. Cultured macrophages were stimulated with lipopolysaccharide and interferon gamma with or without N (G)-nitro-L-arginine methyl ester or N (omega)-hydroxy-nor-L-arginine. Measurement of NO2 - /NO3 - and urea were done using the spectrophotometer. Results: A significantly higher level of nitric oxide production from stimulated macrophages was observed compared to control. There was a decrease in nitric oxide production when stimulated macrophages were treated with the supernatant from activated neutrophils (p<0.05). Conclusion: Arginase from neutrophils can modulate nitric oxide production from activated macrophages which may affect the course of infection by intracellular bacteria.
Original Article
Maryam Rameshrad; Nasrin Maleki-Dizaji; Haleh Vaez; Hamid Soraya; Ailar Nakhlband; Alireza Garjani
Volume 12, Issue 2 , June 2015, Pages 104-116
Abstract
Background: Myocardial dysfunction is one of the major complications in patients with sepsis where there is a relationship between the blood level of cytokines and the onset of myocardial depression. In many cases of sepsis, the presence of Lipopolysaccharide (LPS) has been established. LPS Binding Protein ...
Read More
Background: Myocardial dysfunction is one of the major complications in patients with sepsis where there is a relationship between the blood level of cytokines and the onset of myocardial depression. In many cases of sepsis, the presence of Lipopolysaccharide (LPS) has been established. LPS Binding Protein (LBP) bound endotoxin is recognized by CD14/toll-like receptor-4 (TLR4) complexes in innate immune cells which stimulates TNF-α release. Objectives: To investigate whether isolated rat heart is capable of producing TNF-α locally through TLR4 activation by LPS. Methods: Using langendorff method, LPS in 120 mL of the modified KrebsHenseleit buffer solution (KHBS) at final concentration of 1 µg/mL was perfused at recycling mode. The effect of LPS on cardiac function was evaluated. To assess the TLR4 activity and TNF-α release, western blotting, real time-PCR, and ELISA were used. Results: Compared with control, coronary perfusion pressure (CPP) as well as left ventricular developed pressure (LVDP), maximum and minimum rates of the left ventricular developed pressure (dP/dtmax; dP/dtmin; p<0.001) were depressed to a maximum level after 180 minutes recycling with LPS. This myocardial depression was associated with a significant increase in TLR4 expression (p<0.01), MyD88 activity (p<0.01) and TNF-α (p<0.05) concentration in the heart tissue. Conclusion: The results of this study show that heart is capable of producing TNF-α through TLR4 and MyD88 activation independent of classic immune system and suggest a local immune response.
Original Article
Fahimah Anvari; Feryal Dabagh-Gorjani; Mohammad-Sadegh SoltaniZangbar; Eskandar Kamali-Sarvestani; Zahra Malek-Hosseini; Behrouz Gharesi-Fard
Volume 12, Issue 2 , June 2015, Pages 117-128
Abstract
Background: Pre-eclampsia (PE) is one of the most important and life-threatening pregnancy disorders that affect at least 3-5% of all pregnancies. Imbalance in helper T cell functions may play a role in predisposing to PE or severity of the disease. Elevated frequencies of Th17 cells in the peripheral ...
Read More
Background: Pre-eclampsia (PE) is one of the most important and life-threatening pregnancy disorders that affect at least 3-5% of all pregnancies. Imbalance in helper T cell functions may play a role in predisposing to PE or severity of the disease. Elevated frequencies of Th17 cells in the peripheral blood of PE patients have been reported. Several single nucleotide polymorphisms (SNP) within IL-17 gene have been identified that may affect the IL-17 production. Objectives: To investigate the association between IL-17A (-197A/G) and IL-17F (+7488T/C) gene polymorphisms and susceptibility to PE in a group of Iranian women. Moreover, to study any correlation of the polymorphisms data with the level of IL-17, at mRNA level in the paternal and maternal parts of the placentas and also at protein level in the peripheral and placental blood samples. Methods: A group of 261 PE patients and 278 age-matched healthy women with at least two previous normal pregnancies formed the cases and controls of this study. IL-17A (-197A/G) and IL-17F (+7488T/C) polymorphisms were genotyped using PCR-RFLP method. The protein level of IL-17A was assessed in the sera of 40 PE and 40 healthy women using ELISA method and mRNA expression was also measured in placental samples of 19 PE and 19 control women using Q-PCR technique. Results: Statistical analysis indicated that there were no differences in genotype, allele or haplotype frequencies regarding the studied SNPs between cases and controls. The level of IL-17A was elevated in the placental blood and the fetal tissue at protein and mRNA levels (p< 0.009 and p<0.000, respectively) in PE as compared with the healthy women. Conclusions: The effect of IL-17 cytokine in pre-eclampsia is not due to the studied cytokine polymorphisms but local production of IL-17 might have an effect on the predisposition to the disease.
Original Article
Nasim Hafezi; Abolghasem Ajami; Touraj Farazmandfar; Vahid Hosseini; Reza Alizadeh-Navaei; Mohsen Tehrani
Volume 12, Issue 2 , June 2015, Pages 129-140
Abstract
Background: CD1d presents glycolipid antigens to invariant natural killer T (iNKT) cells. The role of CD1d in the development of peptic ulcer and gastric cancer has not been revealed, yet. Objective: To clarify the expression of alternatively spliced variants of CD1d in peptic ulcer and gastric cancer. ...
Read More
Background: CD1d presents glycolipid antigens to invariant natural killer T (iNKT) cells. The role of CD1d in the development of peptic ulcer and gastric cancer has not been revealed, yet. Objective: To clarify the expression of alternatively spliced variants of CD1d in peptic ulcer and gastric cancer. Methods: Patients with dyspepsia were selected and divided into three groups of non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC), according to their endoscopic and histopathological examinations. H. pylori infection was diagnosed by rapid urease test and histopathology. The expression levels of V2, V4, and V5 spliced variants of CD1d molecule were determined by quantitative Reverse Transcriptase PCR. Results: Relative gene expression levels of V4 were higher in GC patients (n=37) than those in NUD (n=49) and PUD (n=51) groups (p<0.05 and p<0.01, respectively). Moreover, GC patients showed higher expression levels of V5 compared to NUD and PUD groups (p<0.001 and p<0.001, respectively). Positive correlation coefficients were attained between V4 and V5 expression in patients with PUD (r=0.734, p<0.0001) and GC (r=0.423, p<0.01), but not in patients with NUD. Among NUD patients, the expression levels of V4, but not V5, were higher in H. pylori-positive patients than in H. pylorinegative ones (p<0.01). Conclusion: Collectively, both membrane-bound (V4) and soluble (V5) isoforms of CD1d were over-expressed in gastric tumor tissues, suggesting that they are involved in anti-tumor immune responses.
Case Series
Eman Farid; Hasan M Isa; Mohamed Al Nasef; Rawia Mohamed; Huda Jamsheer
Volume 12, Issue 2 , June 2015, Pages 141-148
Abstract
Background: Autoimmune hepatitis (AIH) in childhood has variable modes of presentation, and the disease should be suspected and excluded in all children presenting with symptoms and signs of prolonged or severe acute liver disease. In AIH, the liver biopsy histopathology shows inflammation in addition ...
Read More
Background: Autoimmune hepatitis (AIH) in childhood has variable modes of presentation, and the disease should be suspected and excluded in all children presenting with symptoms and signs of prolonged or severe acute liver disease. In AIH, the liver biopsy histopathology shows inflammation in addition to presence of serum autoimmune antibodies and increased levels of immunoglobulin G (IgG). Objectives: To investigate the situation of childhood autoimmune hepatitis in Bahrain and to compare it with other studies worldwide. Methods: A retrospective study describing the AIH pediatric cases diagnosed during the period of Jan 2005 to Dec 2009. We report the clinical, biochemical, histopathological, and immunological findings, mainly autoimmune profile, in addition to response to treatment, of Bahraini children with autoimmune hepatitis. Results: Five Bahraini children, three females and two males were diagnosed as autoimmune hepatitis during the study period. Their ages at presentation ranged from 9 to 15 (median 10.6) years. One of our patients had a fulminating type. Two had other autoimmune related conditions, namely autoimmune sclerosing cholangitis and ulcerative colitis. All were AIH type 1. Variable response to conventional immunosuppressive therapy was found, from an excellent response with good prognosis, to cirrhosis, hepatic failure and liver transplantation. Conclusion: Childhood AIH is a rare medical problem in Bahrain, with both sexes affected and a variable response to immunosuppressive therapy.
Short Paper
Tawfik Jasim Mohammad Al-Marzook; Batool Mutar Mahdi; Hyam Raouf; Haider Hashim Zalzala; Laheeb Ali Abid; Zena Nehad
Volume 12, Issue 2 , June 2015, Pages 149-155
Abstract
Background: Cholecystitis is one of the major digestive diseases. Its prevalence is particularly high in some populations. Significant risk factors associated with cholecystitis include age, sex, obesity, diet, parity and type 2 diabetes. Objective: To determine the association between HLA-DRB1 and cholecystitis. ...
Read More
Background: Cholecystitis is one of the major digestive diseases. Its prevalence is particularly high in some populations. Significant risk factors associated with cholecystitis include age, sex, obesity, diet, parity and type 2 diabetes. Objective: To determine the association between HLA-DRB1 and cholecystitis. Methods: This casecontrol study included forty Iraqi Arab patients who had cholecystitis with multiple calculi treated by cholecystectomy admitted in the surgical ward at Al-Kindy Teaching Hospital Baghdad between September -2013 to June -2014. The control group consisted of forty healthy volunteers among the staff of Al-Kindy College of Medicine. Control and cholecystitis patients groups were typed for identifying the DRB1* alleles using DNA-based methodology (PCR-SSOP). Results: There was an increased frequency of HLA-DRB1*0301 in patients with cholecystitis compared with healthy controls (p=0.0442, odd ratio=4.1111, 95% CI: 1.0372-16.2949). Conclusion: HLADRB1*0301, as a genetic factor, seems to have an association with cholecystitis.
