Original Article
Esmaeil Allahmoradi; Saeid Taghiloo; Mohsen Tehrani; Hadi Hossein-Nattaj; Ghasem Janbabaei; Ramin Shekarriz; Hossein Asgarian-Omran
Volume 14, Issue 4 , Autumn 2017, Pages 257-269
Abstract
Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world. This health problem is caused due to the accumulation of mature B-lymphocytes in the peripheral blood and bone marrow. In the course of cancer, CD4+ T cells become “exhausted” and characterized ...
Read More
Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world. This health problem is caused due to the accumulation of mature B-lymphocytes in the peripheral blood and bone marrow. In the course of cancer, CD4+ T cells become “exhausted” and characterized with poor effector functions and the expression of multiple inhibitory receptors. Objective: To investigate the frequency and functional properties of exhausted CD4+ T lymphocytes in patients with CLL. Methods: Peripheral blood mononuclear cells were obtained from 25 untreated CLL patients and 15 healthy volunteers. CLL patients were clinically classified according to the Rai staging system. The frequency of CD4+/Tim-3+/PD-1+ cells was obtained by flow cytometry. To evaluate cell proliferation and cytokine production, CD4+ T cells were isolated and stimulated with phytohemagglutinin and PMA/ionomycin. Concentrations of IL-2, IFN-γ, TNF-α, and IL-10 were measured in the culture supernatants of stimulated cells by the ELISA technique. Results: The percentage of CD4+/Tim-3+/PD-1+ cells was significantly higher in CLL patients than that of healthy controls. CD4+ T cells from CLL patients showed lower proliferative responses, a lower production of IL-2, IFN-γ, and TNF-α, and a higher production of IL-10, compared to healthy controls. CD4+ T cells from CLL patients in advanced clinical stages showed more exhaustion features than those of early stages. Conclusion: Given that the exhaustion phase of T cells can be reversible, targeted blocking of immune inhibitory molecules could be a promising tool to restore the host immune responses against leukemic cells in CLL.
Original Article
Aziz Mahmoudzadeh; Ali Akbar Pourfathollah; Mohammad Hossein Karimi; Seyed Mohammad Moazzeni
Volume 14, Issue 4 , Autumn 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 ...
Read More
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.
Original Article
Volume 14, Issue 4 , Autumn 2017, Pages 281-292
Abstract
Background: Hepatitis viruses are non-cytopathic viruses that lead to the infection and pathogenesis of liver diseases as a result of immunologically mediated event. Objective: To investigate the expression of human inflammatory cytokines in chronic hepatitis B patients according to the severity of the ...
Read More
Background: Hepatitis viruses are non-cytopathic viruses that lead to the infection and pathogenesis of liver diseases as a result of immunologically mediated event. Objective: To investigate the expression of human inflammatory cytokines in chronic hepatitis B patients according to the severity of the infection. Methods: We recruited a total of 120 patients, 40 of whom from cirrhotic, 40 non-cirrhotic, and 40 acute flare chronic hepatitis B and 40 healthy controls. For all groups total cellular RNA was extracted from whole blood samples, genomic DNA was eliminated, and cDNA was synthesized using the RT2 first strand kit, as instructed by the manufacturer. The real-time profiler PCR array was performed on an a master cycler ep realplex and the data were analyzed using an online data analysis software. Results: Non-cirrhotic chronic hepatitis B patients were found to significantly upregulate interleukin 10 receptors that regulate the balance between T helpers 1 and 2. On the other hand, patients with cirrhosis were found to have significant upregulated interleukin 3 gene expression. Conclusion: Our finding suggests that upregulation of anti-inflammatory and downregulation of pro-inflammatory cytokines may play a roles in the progression of non-cirrhotic chronic hepatitis B patients to cirrhotic and acute flare. However, a multi-center study with a larger sample size is needed to confirm our findings.
Original Article
Behnam Mohammadi-Ghalehbin; Gholamreza Hatam; Bahador Sarkari; Mehdi Mohebali; Zabih Zarei; Shahab Bohlooli
Volume 14, Issue 4 , Autumn 2017, Pages 293-305
Abstract
Background: Canine visceral leishmaniasis (CVL) caused by Leishmania infantum is endemic in the northwest and south of Iran. An appropriate vaccine can help to prevent and control visceral leishmaniasis in both humans and animals. Few studies have confirmed that the fucose-mannose ligand (FML) antigen ...
Read More
Background: Canine visceral leishmaniasis (CVL) caused by Leishmania infantum is endemic in the northwest and south of Iran. An appropriate vaccine can help to prevent and control visceral leishmaniasis in both humans and animals. Few studies have confirmed that the fucose-mannose ligand (FML) antigen of Leishmania donovani produced protective immunity in dogs against CVL. Objective: To evaluate the immune responses of vaccinated dogs against FML antigen of L. infantum. Methods: We isolated the FML antigen from native L. infantum and vaccinated the dogs with FML-saponin in an endemic area of VL in Iran to evaluate the immune responses of vaccinated dogs against this antigen. Results: Our results indicated a significant increase in the expression of IFN-γ, IL-10 and IL-13, but not IL-12A, gene transcripts in PBMCs of FML-saponin vaccinated dogs in comparison with controls. Our findings showed a significant difference in the ratio of IFN-γ/IL-10 mRNA expression in FML-saponin vaccinated dogs in comparison with two control groups. Moreover, a significant level of anti-FML antibodies was detected in serum of vaccinated dogs. Conclusion: These findings showed that FML-saponin stimulates both Th1 and Th2 immune responses with predominant Th1 and strong humoral immune responses to produce protective immunity against CVL.
Original Article
Behrouz Gharesi-Fard; Maryam Zare; Eskandar Kamali-Sarvestani
Volume 14, Issue 4 , Autumn 2017, Pages 306-315
Abstract
Background: Multiple Sclerosis (MS) with four different types is one of the well studied autoimmune diseases of the central nervous system. Generally, two-thirds of MS patients are females who are at risk of pregnancy-related complications. Inappropriate responses of mother’s immune system, ...
Read More
Background: Multiple Sclerosis (MS) with four different types is one of the well studied autoimmune diseases of the central nervous system. Generally, two-thirds of MS patients are females who are at risk of pregnancy-related complications. Inappropriate responses of mother’s immune system, such as antibody production against placental proteins, may lead to pregnancy-related disorders. The association between pregnancy complications and some autoantibodies including anti-phospholipid and anti-angiotensin II type-1 receptor antibodies are clear examples in this regard. Objective: To investigate the probable placental antigens that might be targeted by the antibodies in the sera of MS patients. Methods: Total placental proteins were extracted from normal fresh placentas and were separated using two-dimensional gel electrophoresis (2-DE) technique. The separated proteins were transferred onto a Polyvinylidene Fluoride (PVDF) membrane and blotted with the pooled sera of MS women or healthy controls (20 individuals in each group). The differentially blotted spot was identified by mass spectrometry and confirmed by western blot technique. Results: The results indicated that the women afflicted with MS had an antibody against placental HSP70kDa protein 5 (GRP78). Conclusion: In the present study, a new placental autoantigen candidate, which was targeted by antibody present in MS women sera, was found. The clinical importance of this finding regarding pregnancy complications in MS patients should be investigated by further experiments.
Original Article
Fatemeh Ahmadi-Motamayel; Zeynab Bayat; Mehrdad Hajilooi; Soroosh Shahryar-Hesami; Ali Mahdavinezhad; Lida Samie; Ghasem Solgi
Volume 14, Issue 4 , Autumn 2017, Pages 316-324
Abstract
Background: Oral Lichen Planus (OLP) is a chronic autoimmune disease that could be considered as a potential premalignant status. Objective: To evaluate the miRNA-146a and miRNA-155 expression levels in patients with oral Lichen planus lesions compared to healthy subjects with normal oral mucosa. Methods: ...
Read More
Background: Oral Lichen Planus (OLP) is a chronic autoimmune disease that could be considered as a potential premalignant status. Objective: To evaluate the miRNA-146a and miRNA-155 expression levels in patients with oral Lichen planus lesions compared to healthy subjects with normal oral mucosa. Methods: Forty patients with oral lichen planus and 18 healthy age and gender-matched controls were recruited in this case-control study. Oral lichen planus was diagnosed clinically and pathologically. The expression levels of two miRNAs in peripheral blood samples were determined using commercial TaqMan MicroRNA Assays. Relative quantification of gene expression was calculated by the 2-ΔΔct method. Results: The expression levels of miRNA-146a and miRNA-155 in patients with oral Lichen planus were significantly higher than the of the healthy control group. Also, a direct but insignificant correlation was found between miRNA-155 and miRNA-146a expression levels among the patient group. Conclusion: Our findings indicate that miRNA-146a and miRNA-155 could be potential biomarkers for the immunopathogenesis of oral lichen planus.
Original Article
Elisa Vintiñi; Marcela Medina
Volume 14, Issue 4 , Autumn 2017, Pages 325-339
Abstract
Background: Polyinosinic:polycytidylic acid (Poly-IC) has been used as a viral stimulus to mimic in vivo and in vitro infection induced by some viruses. Objective: To determine whether non-viable Lactobacillus casei CRL431 (LcM) can modulate the immune response induced by Poly I:C in co-culture ...
Read More
Background: Polyinosinic:polycytidylic acid (Poly-IC) has been used as a viral stimulus to mimic in vivo and in vitro infection induced by some viruses. Objective: To determine whether non-viable Lactobacillus casei CRL431 (LcM) can modulate the immune response induced by Poly I:C in co-culture models of peripheral blood mononuclear cells (PBMC) and A549 cells. Methods: T and NK cell activation was evaluated by flow cytometry and levels of TNF-α, IFN-γ, IL-10, IL-29, and IL-17 by ELISA. Cells in direct contact with A549 (PBMC-A549) and cells with no contact with it (PBMC//A549) were used for this purpose. PBMCs alone and both co-culture systems were stimulated for 24 h with the following stimuli: LPS (10 µg/ml), LcM (106 UFC/ml), Poly I:C (2 µg/ml), Poly I:C+LcM, and LcM (3 h)+Poly I:C. Moreover, unstimulated cells were used as a control. Results: Poly I:C and LcM (3 h)+Poly I:C in PBMC-A549 showed a significant increase in the percentage of CD8+ expression (p<0.05). All stimuli induced significant activation from T CD4+, CD8+ cells compared with unstimulated PBMCs in both co-culture cells system. However, activation percentages were higher in direct co-culture. Poly I:C induced a higher level of pro-inflammatory TNF-α and IFN-γ cytokines as well as IL-17 and IL-29 with lower IL-10 levels in both co-culture systems while LcM induced a beneficial pattern of cytokines that would regulate Poly I:C effect. Conclusion: This in vitro model allowed us to highlight the potential of LcM as a modulator of anti-viral immune response and suggest its potential use in formulations against RNA respiratory viruses.
Short Paper
Marilina Tampoia; Letizia Abbracciavento; Marella Morrone; Ruggiero Fumarulo
Volume 14, Issue 4 , Autumn 2017, Pages 340-349
Abstract
Background: Recent studies have shown that cytokines have an important role in the pathogenesis of inflammatory diseases and can be used as prognostic markers. Objective: To evaluate the IL-6/IL-10 ratio in patients with Inherited Epidermolysis Bullosa (EB) as a prognostic marker. Methods: Serum levels ...
Read More
Background: Recent studies have shown that cytokines have an important role in the pathogenesis of inflammatory diseases and can be used as prognostic markers. Objective: To evaluate the IL-6/IL-10 ratio in patients with Inherited Epidermolysis Bullosa (EB) as a prognostic marker. Methods: Serum levels of IL-6 and IL-10 were measured in 13 patients with recessive dystrophic EB (RDEB) as well as 10 with EB Simplex (EBS), and in 18 healthy subjects. Receiver Operating Characteristics (ROC) analyses were used to assess the diagnostic accuracy of the IL-6/IL-10 ratio for detecting severe form of EB. Results: The IL-6/IL-10 ratio was statistically higher in RDEB patients than in EBS patients and healthy subjects. The IL-6/IL-10 ratio significantly correlated with BEBS score. Conclusion: Our findings suggest that IL-6/IL-10 ratio >5.6 has a good diagnostic accuracy to identify patients with the highest severity of disease.