Aihong Zhang; Quanhui Zheng
Abstract
Background: Understanding the effects of epigenetic factors on the pathogenesis of rheumatoid arthritis (RA) is important for the early diagnosis and therapeutic intervention of this disease. MicroRNA-150 (miR-150) exerts an important influence on the development and function of lymphocytes. However, ...
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Background: Understanding the effects of epigenetic factors on the pathogenesis of rheumatoid arthritis (RA) is important for the early diagnosis and therapeutic intervention of this disease. MicroRNA-150 (miR-150) exerts an important influence on the development and function of lymphocytes. However, the role of miR-150 in the pathogenesis of RA remains unclear.Objective: To explore the role of miR-150 in the pathogenesis of RA and the related immune mechanism.Methods: In this study, we used miR-150 knock-out (miR-150KO) and created animal models of RA. Flow cytometry, immunohistochemistry, and real-time RT-PCR were employed to assess the frequency of T cell subsets and cytokines expression.Results: Compared to wild-type (WT) mice, the onset of RA was postponed and the incidence of RA was reduced in miR-150KO mice. The expression of IL-4 and IFN-γ significantly increased while the expression of IL-17 decreased significantly in NKT and CD4+ T cells of KO mice compared to that of WT mice after RA induction. In addition, the expression of IL-4 and IFN-γ increased while the expression of IL-17 decreased significantly in the joint tissues of KO mice compared to that of WT mice. Furthermore, the mRNA expression of TNF-α and IL-17 decreased significantly in the synovial fluid cells of KO mice compared to that of the WT mice after RA induction.Conclusion: MiR-150 deficiency decreases the expression of IL-17 in T cells and joint tissues, and alleviates the occurrence and progression of RA in mice.
Mehrdad Shavandi; Yasaman Yazdani; Shirin Asar; Arash Mohammadi; Ehsan Mohammadi-noori; Amir Kiani
Abstract
Background: Rheumatoid Arthritis (RA) is a systemic chronic autoimmune disease. Several inflammatory agents play key roles in RA pathogenesis, among which tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) are of great importance. Silymarin is a potent anti-oxidant extracted ...
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Background: Rheumatoid Arthritis (RA) is a systemic chronic autoimmune disease. Several inflammatory agents play key roles in RA pathogenesis, among which tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) are of great importance. Silymarin is a potent anti-oxidant extracted from Silybummarianum L. seeds. Objective: To study the effect of silymarin on serum levels of TNF-α and IL-1β in patients with RA. Methods: Patients with stable RA received 140 mg of silymarin, 3 times a day, for 3 months. Serum samples were collected before and after the treatment. Both TNF-α and IL-1β serum levels were measured by ELISA. Results: 42 patients (14.3% male, and 85.7% female, with a mean age of 47.59±12.8 years old) completed the treatment course. There was no significant difference in the overall mean concentration of either TNF-α (p=0.14) or IL-1β (p=0.27) in all 42 patients after the treatment with silymarin. Conclusion: The addition of silymarin to the treatment regimen of patients with stable RA has no significant effect on the serum levels of TNF-α and IL-1β, however, this study needs further evaluation with a larger sample size.
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.
Roya Adelnia; Fatemeh Shafiee
Abstract
Background: Anakinra (Kineret®), an IL-1 receptor antagonist, is the first FDA approved biologic drug for antagonizing IL-1 effects in patients with Rheumatoid arthritis. Notably, the less expensive production of this drug might help reduce the final therapeutic costs. Objectives: This study aimed ...
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Background: Anakinra (Kineret®), an IL-1 receptor antagonist, is the first FDA approved biologic drug for antagonizing IL-1 effects in patients with Rheumatoid arthritis. Notably, the less expensive production of this drug might help reduce the final therapeutic costs. Objectives: This study aimed to evaluate the possibility of producing biologically active recombinant IL-1Ra by a single step purification procedure mediated by a self-cleavable intein. Methods: Soluble expression of the rIL-1Ra was performed in E. coli BL21 (DE3) in fusion to intein1 of pTWIN-1 vector and its cleavage induction using an elution buffer (pH 6.8) at room temperature. Evaluation of the antagonizing efficacy of this protein in various concentrations, was performed on A375 and HEK293 cells treated by a constant concentration of IL-1β (2ng/mL). Results: IPTG induction of E. coli BL21 (DE3) transformed with the recombinant pTWIN-1, revealed a band approximately in 45 kDa, which is related to the intein1-rIL-1Ra fusion protein in the SDS-PAGE. Moreover, protein purification was confirmed by observing a band in 18 kDa. Finally, the percentage of inhibition effects of rIL-1Ra and Kineret® against IL-1β was not statistically significant in IL-1-responsive A375 cells. The inhibition percentage was calculated as 86% in cells treated with 15µg/mL of rIL-1Ra, which it was 96% for the inhibitory effects of the standard drug. Conclusion: In this study, biologically active soluble rIL1-Ra was successfully produced with high purity through a one-step procedure. This method can reduce the cost and time of production for this protein and might be applicable for producing other biologics.
Nayyereh Saadati; Mandana khodashahi; Zahra Rezaieyazdi; Maryam Sahebari; Zeinab Saremi; Saeed Mohammadian Haftcheshmeh; Houshang Rafatpanah; Maryam Salehi
Abstract
Background: Rheumatoid arthritis (RA) is described as a systemic and chronic autoimmune disease characterized by inflammatory polyarthritis. Lymphocyte-activation gene 3 (LAG3) is a membrane glycoprotein expressed on activated, exhausted, and regulatory T cells. LAG3 plays a major role in the function ...
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Background: Rheumatoid arthritis (RA) is described as a systemic and chronic autoimmune disease characterized by inflammatory polyarthritis. Lymphocyte-activation gene 3 (LAG3) is a membrane glycoprotein expressed on activated, exhausted, and regulatory T cells. LAG3 plays a major role in the function of Treg cells. LAG3 also has a soluble form (sLAG3) with a controversial role. Objective: To evaluate the serum level of sLAG3 in rheumatoid arthritis patients in comparison with healthy subjects and assess its association with the disease activity. Methods: This cross-sectional study was performed on 105 patients with RA referred to Ghaem hospital of Mashhad, Iran. We divided the participants into four groups: 1) 35 untreated patients with newly diagnosed RA, 2) 35 active RA patients, 3) 35 patients in the remission phase of the disease, and 4) 35 healthy individuals matched in terms of age and sex. After completing the interview and questionnaire, the sLAG3 was evaluated by commercial ELISA. Results: The serum level of sLAG3 significantly increased in RA patients (76.78 ng/ml) as compared with the healthy participants (51.67, p=0.002). However, there was no significant difference between RA patients in the remission phase of the disease (114.11 ng/ml) and those with moderate to high disease activity (63.06 ng/ml, p=0.076). Conclusion: This study provided insights into the role of sLAG3 in the immunopathogenesis of RA disease, but further investigations are also warranted.
Hamidreza Ebrahimiyan; Shayan Mostafaei; Saeed Aslani; Ahmadreza Jamshidi; Mahdi Mahmoudi
Zeinab Kadkhoda; Aliakbar Amirzargar; Zahra Esmaili; Mahdi Vojdanian; Solmaz Akbari
Volume 13, Issue 3 , September 2016, , Pages 197-203
Abstract
Background: Periodontitis and rheumatoid arthritis (RA) share a number of clinical and pathologic features, one of which is the presence of the tumor necrosis factor alpha (TNF-α)-induced bone resorption that is involved in the pathogenesis of both. Objectives: To investigate the effect of TNF-α ...
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Background: Periodontitis and rheumatoid arthritis (RA) share a number of clinical and pathologic features, one of which is the presence of the tumor necrosis factor alpha (TNF-α)-induced bone resorption that is involved in the pathogenesis of both. Objectives: To investigate the effect of TNF-α blockade on periodontal conditions in patients with active RA. Method: The periodontal statuses of 36 patients (26 females, 10 males) diagnosed with active RA were evaluated both before and after anti-TNF-α therapy. Gingival index, bleeding on probing (BOP), probing pocket depth (PPD), oral hygiene index (OHI), and levels of TNF-α in gingival crevicular fluid (GCF) were measured at the baseline and 6 weeks after the treatment. Wilcoxon signed ranked test was used for statistical analyses. Results: Based on OHI (p=0.860), the level of plaque control did not change during the study period, but there was a significant reduction in gingival inflammation based on the mean BOP (p=0.049) and GI (p=0.036) before and after 6 weeks of anti-TNF-α therapy. The mean PPD index did not significantly differ at the baseline and 6 weeks after treatment (p=0.126). Conclusion: Anti-TNF-α therapy might have a desirable effect on periodontal conditions and might reduce TNF-α level in GCF of patients with RA.
Hamid-Reza Zare; Mojtaba Habibagahi; Akbar Vahdati; Zahra Habibagahi
Volume 12, Issue 3 , September 2015, , Pages 166-175
Abstract
Background: Patients with rheumatoid arthritis (RA) suffer from wide ranges of autoimmune reactions in joints. The mechanism of which is generally unknown and maybe associated with Treg deregulation. Objective: To compare the frequency of nTregs in peripheral blood of patients with active rheumatoid ...
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Background: Patients with rheumatoid arthritis (RA) suffer from wide ranges of autoimmune reactions in joints. The mechanism of which is generally unknown and maybe associated with Treg deregulation. Objective: To compare the frequency of nTregs in peripheral blood of patients with active rheumatoid disease with healthy individuals. Methods: Twenty five newly diagnosed patients with active RA disease were selected based on the clinical and laboratory criteria before starting their therapies. Treg cells in peripheral blood samples were enumerated by immune staining and flowcytometry analysis. Results: Clinical and laboratory results were in favor of active disease in all the studied patients although they showed variations in Disease Activity Score-28 (DAS-28). Compared to the healthy controls, RA patients had significantly lower frequency of CD4+ CD25hi or CD4+ CD25+ FoxP3+ natural regulatory T cells. In spite of that, there were no significant differences between patients and healthy controls in respect to the CD4/CD8 ratio. Interestingly, more CD4+ CD25- FoxP3+ cells were found in peripheral blood of patients. The frequencies of the Tregs did not show strong associations with the DAS-28. Conclusion: We showed lower abundance of nTregs in peripheral blood of RA patients which highlights the significance of these cells in RA.
Ali Asghar Ebrahimi; Hamid Noshad; Shahram Sadreddini; Mohammad Saeid Hejazi; Yashar Mohammadzadeh Sadigh; Yashar Eshraghi; Morteza Ghojazadeh
Volume 6, Issue 3 , September 2009, , Pages 147-153
Abstract
Background: Rheumatoid arthritis (RA) is a chronic multisystem autoimmune disease common in all races and ethnics. Cytokines and cytokines receptors play an important role in RA pathogenesis and clinical presentation. Objective: To investigate the serum levels of TNF-α, TNF-α RI, TNF-α ...
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Background: Rheumatoid arthritis (RA) is a chronic multisystem autoimmune disease common in all races and ethnics. Cytokines and cytokines receptors play an important role in RA pathogenesis and clinical presentation. Objective: To investigate the serum levels of TNF-α, TNF-α RI, TNF-α RII and IL-12 in RA patients and healthy control group. Methods: In this study 43 patients fulfilling the revised criteria of American College of Rheumatology (ACR) for RA and 13 healthy cases as a control group were selected for TNF-α, TNF-αRI, TNF-αRII and IL-12 serum level analysis. The patients' age was 42.2 ± 22 and the age of healthy group was 40.1 ± 19.2 years (p=0.1). The pa-tients had an active disease with at least six swollen and ten tender joints. Minimum ESR was 28 mm at first hours of the morning. Early morning stiffness in patients lasted longer than 45 minutes. Results: Our study showed that IL-12 serum level of the pa-tients (91.69 ± 43.07 ρg/ml) and control (61.79 ± 40.08 ρg/ml) group was significantly different (p<0.001). The serum level of TNF-αRI was 2.36 ± 0.77 ng/ml in the patient and 1.73 ± 0.37 ng/ml in the control group (p<0.01). TNF-αRII serum concentration in patients was 8.89 ± 2.3 ng/ml, while that of control group was 7.06±1.30 ng/ml (p=0.03). The serum level of TNF-α in patients was 32.90 ± 19.27 ρg/ml and that of the control group was 24.27± 8.28 ρg/ml (p=0.08) with no significant difference between the two. Conclusions: It is concluded that IL-12, TNF-αRI and TNF- αRII serum con-centrations are more important and better predictive factors than TNF-α in RA course and in the active forms of the disease.
Abbas Ali Pourazar; Alireza Andalib; Farzad Qreizy; Hadi Karimzadeh; Ahmad Ghavami-Nejad; Behshad Pournasr-Khakbaz
Volume 2, Issue 2 , June 2005, , Pages 91-96
Abstract
Background: Inappropriate activation or blockage of the inhibition of complement system could cause tissue damages in autoimmune diseases particularly rheumatoid arthritis (RA). Defect in complement component regulation may cause damages to tissues, on the other hand, or the damaged tissue might affect ...
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Background: Inappropriate activation or blockage of the inhibition of complement system could cause tissue damages in autoimmune diseases particularly rheumatoid arthritis (RA). Defect in complement component regulation may cause damages to tissues, on the other hand, or the damaged tissue might affect the unnecessary activation of complement components. Objective: To investigate the expression of CD55 and CD 59 complement regulatory proteins in RA patients. Subjects and Methods: Fifty proved rheumatoid arthritis patients participated in this study and their blood were collected for investigations. CD55 and CD59 molecules expression on the erythrocytes was assayed using primary monoclonal antibody and secondary FITC conjugated Ab, then the prepared samples were run with a FACSCalibur flowcytometer (Becton-Dickinson) and the obtained data was analyzed using a Cell Quest software package. To evaluate the complement function, CH50 was performed using patient sera. All experiments were done with a matched healthy volunteer group. Results: The mean fluorescence intensity for CD55 was 27.6 ± 13.4 arbitrary unit for patients and 68.5 ± 10.5 for healthy group. CD59 mean fluorescence intensity was 314 ± 83 in patient group and 508 ± 56 in healthy volunteers. In addition, there was a significant difference between CH50 in patients (54.5 ± 15.5) and in healthy group (110 ± 20). A significant correlation between CD55 and CD59 expansion on the patient erythrocytes was found (P = 0.00, r = 0.576). No association was found between CD59, or CD55 with CH50 (P > 0.05). Conclusion: The expression of CD55 and CD59 is down-regulated on erythrocytes of patients with RA. Change in expression of regulatory complement components in RA may be a useful key for the assessment of disease progression or in patients' follow-up.