Comparison of the intima-media thickness of the common carotid artery in patients with rheumatoid arthritis: A single-center cross-sectional case-control study, and a brief review of the literature.

Background and Aim: Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease affecting 0.5%-1% of adults worldwide. The carotid intima-media thickness (CIMT) is a simple, reliable, noninvasive marker for subclinical atherosclerosis. The aim of this study was to compare the intima-media thickness of the common carotid artery in patients with RA with that of healthy patients. Methods: In this case-control study, subjects were recruited from the patients who presented to a private rheumatology clinic. RA was documented by a rheumatologist. All subjects underwent an ultrasound examination of the carotid artery to assess CIMT. Subjects with RA filled out the disease activity score (DAS28) questionnaire. Results: Sixty-two subjects (31 subjects with RA and 31 healthy subjects) took part in the study. The mean age of the subjects in the RA and the control groups was 42.39 ± 12.98 and 44.48 ± 13.56 years, respectively. Values of CIMT were significantly greater in RA subjects compared with their healthy counterparts (p < 0.001). The CIMT increased significantly with increased disease severity (r = 0.73). Subjects were divided into two age groups (≤40 and >40 years). A comparison of CIMT in the mentioned subgroups revealed a remarkable difference in CIMT values between those of the RA patients and those of their control counterparts in both age groups (p = 0.002 and p < 0.001 for those below and above 40 years, respectively). Conclusion: CIMT could be used as an efficient clinical index for identifying the early stages of atherosclerosis and predicting cardiovascular events following atherosclerosis in RA patients.

The Effects of Mesenchymal Stem Cells on the Gene Expression of TGF-beta and IFN-gamma in Patients with Rheumatoid Arthritis.

The therapeutic and immunomodulatory potential of mesenchymal stem cells (MSCs) in rheumatoid arthritis (RA) has attracted considerable scientific attention in recent decades. This study aimed to evaluate the expression of genes encoding interleukin (IL)4 and IL10, as well as interferon-gamma (IFNG) and transforming growth factor beta (TGFB1) in refractory RA patients following intravenous injection of autologous bone marrow-derived MSCs (BM-MSCs). This study was registered in Iranian Registry of Clinical Trials (IRCT) (2015102824760N1) and ClinicalTrials.gov (identifier: NCT03333681). Blood samples were taken from 13 patients before and 1 and 6 months after the MSC injection to evaluate the clinical manifestations, paraclinical factors, and expression of IL4, IL10, IFNG, and TGFB1 genes employing the SYBR Green real-time reverse-transcriptase polymerase chain reaction (RT-PCR) technique. There was a significant increase in the expression of TGFB1 at 1 and 6 months after the MSC injection compared to that in the baseline, while the expression of IL4 and IL10 did not change significantly. On the other hand, the expression of IFNG increased significantly after 1 month but decreased significantly at 6 months compared to 1 month after the intervention. Nevertheless, it showed no significant decrease compared to the baseline. A significant decrease was observed for the expression of IFNG 6 months after the injection compared to that after 1 month, which was in concordance with the rise in the expression of the TGFB1 gene. A significant change in the gene expression of TGFB1 and IFNG in our study was consistent with the amelioration of clinical manifestations, suggesting a mechanism of action for MSCs in the treatment of RA.

Influence of biologic and conventional disease-modifying antirheumatic drugs on COVID-19 incidence among rheumatic patients during the first and second wave of the pandemic in Iran.

Introduction: During the SARS-CoV-2 virus pandemic, immunosuppressive agents in treating chronic disease have become a concern, and rheumatic patients are not an exception. The controversies about the deteriorating effects of such medications led this study to evaluate the influence of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) on the incidence of COVID-19 infection in rheumatic patients. Material and methods: In the present cohort-analytical study, 512 patients with rheumatic diseases were enrolled during the COVID-19 pandemic (2020-2021). The incidence of COVID-19 infection was diagnosed according to the definition of the Iranian Ministry of Health. The frequency of COVID-19 infection in patients treated with biological and conventional DMARDs and glucocorticosteroids were compared. Results: Among 512 rheumatic patients, 19.9% were definitely infected with COVID-19, and 23.3% of infected patients were hospitalized. Only one patient with vasculitis died during the two outbreaks. Our study showed that adding biologic DMARDs to conventional DMARDs did not increase the risk of COVID-19 infection. However, unlike biologic DMARDs, in conventional DMARDs, methotrexate increased, and hydroxychloroquine decreased COVID-19 infection. Regression analysis showed that prednisolone at a dosage higher than 10 mg/day increased the risk of COVID-19 infection 5-fold; hydroxychloroquine had a protective impact and reduced the risk of infection by 40%. Conclusions: Biologic DMARDs and the type of selected rheumatic diseases in our study did not influence the susceptibility to COVID-19 infection. Prednisolone raised the coronavirus infection, and hydroxychloroquine played a protective role in the current study. Most of our patients showed good adherence to the health protocols. Further studies after worldwide vaccination are now required to reevaluate the influence of rheumatic diseases and DMARDs on COVID-19 infection.

Curcumin as an effective suppressor of miRNA expression in patients with knee osteoarthritis.

Objective: Osteoarthritis is the most common disease in the group of joint diseases, and its incidence is directly related to aging. Given the anti-inflammatory effects of curcumin as an active ingredient of turmeric, we aimed to investigate the effects of this compound in a new curcumin nanomicelle formula named SinaCurcumin® on the expression of microRNAs (miRNAs) involved in immune responses of patients with osteoarthritis. Materials and Methods: We divided 30 patients with osteoarthritis into two groups namely, nano curcumin-receiving (15 patients) and placebo-receiving (15 patients) and we studied them for 3 months. The Iranian Registry of Clinical Trials (IRCT) approved our study with the IRCT registry No. IRCT20151028024760N4. We evaluated the rates of the expression of microRNAs 146, 155, 16, and 138 employing SYBR Green Real-Time PCR method. Results: The expression of miRNAs 155, 138, and 16 revealed a significant reduction in the curcumin-receiving group (p=0.002, p=0.024 and p=0.0001 respectively). Conclusion: Our research data indicated that the consumption of curcumin in patients with osteoarthritis could affect the immune system partially via altering the expression of microRNAs and cytokines.

Significant Effect of Crocin on the Gene Expression of MicroRNA-21 and MicroRNA-155 in Patients with Osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis associated with gradual joint destruction. The current treatment aims to alleviate pain and inflammation and improve the quality of life. Crocin is an active ingredient in saffron, with anti-inflammatory properties. MicroRNAs are small, non-coding RNAs that regulate gene expression. We aimed to evaluate the effect of crocin on the gene expression of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 in OA patients and compare it with a placebo. This study was approved and registered in the Iranian Registry of Clinical Trials (2015021910507N2) and ClinicalTrials.gov identifier: NCT03375814. Forty OA patients were randomly divided into two equal groups, receiving either crocin or placebo. Peripheral blood samples were collected before and four months after the intervention. The pain was assessed using the visual analog scale, and laboratory tests included C-reactive protein and erythrocyte sedimentation rate. The expression levels of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 genes were evaluated by SYBR Green real-time PCR. The results showed that the gene expression levels of microRNA-21 and microRNA-155 in patients receiving crocin were significantly decreased and increased, respectively. No significant changes were observed in microRNA-146a and microRNA-223 gene expression levels. In conclusion, crocin's anti-inflammatory role might be partly attributed to its effects on the gene expression of microRNA-21 and microRNA-155.

A Significant Reduction in the Plasma Levels and Gene Expression of CCL2 in Patients with Osteoarthritis following Intervention with Krocina™.

Background: inflammatory chemokines such as CCL2 and CCL5 are involved in the progress of osteoarthritis. Crocin with antioxidant and anti-inflammatory properties can reduce the symptoms of osteoarthritis (OA). This study was performed investigate the effect of Krocina™, on the gene expressions and plasma levels of CCL2 and CCL5 in OA patients. Methods: The study included 35 patients that were randomized in the Krocina™ and placebo groups. The intervention was Krocina™ 15mg daily for four months. Clinical and paraclinical parameters were measured. CCL2 and CCL5 genes expression and plasma levels were determined using the SYBR Green Real-Time RT-PCR and Enzyme-linked Immunosorbent Assay (ELISA) techniques. Results: The C-reactive protein (CRP) value in the Krocina™ group and the visual analogue scale (VAS) value in the Krocina™ and placebo groups decreased significantly after the intervention. The gene expression of CCL2 in the Krocina™ and placebo groups decreased significantly. On the contrary, the gene expression of CCL5 in the Krocina™ and placebo groups increased significantly. Moreover, the plasma levels of CCL2 in the Krocina™ and placebo groups decreased meaningfully. There was no difference regarding the plasma levels of CCL5 within the Krocina™ and placebo groups before and after the intervention in either of the groups. Conclusion: Administration of Krocina™ reduced the clinical signs of inflammation and CRP and VAS value. Also, Krocina™ significantly decreased the plasma levels and gene expression of CCL2 in osteoarthritis patients.

A Significant Increase in the Gene Expression of GATA-3 Following the Treatment of Osteoarthritis Patients with Crocin.

Osteoarthritis (OA) is known to be the most prevalent form of joint disease. We conducted this clinical trial to investigate the effects of KrocinaTM, a natural product containing crocin, on the gene expression of unique transcription factors of various T cell subsets in patients with OA. We collected 40 peripheral blood samples of OA patients receiving Krocina™ and equal number of those who took a placebo (IRCT2015021910507N2, NCT03375814). RNA extraction was performed from the cultured peripheral blood mononuclear cells of the OA patients who received Krocina™ and placebo and SYBR Green Real-time PCR technique was applied to assess the relative gene expression of T-bet, GATA3, ROR-γt, and FOXP3 as the unique transcription factors of various T cell subsets. The relative gene expression of T-bet and ROR-γt insignificantly decreased in the Krocina™ receiving group as compared to the placebo group. In addition, the relative gene expressions of GATA-3 and FOXP3 after the treatment with KrocinaTM showed a significant and insignificant increase, respectively. Moreover, an insignificant decrease was observed in the gene expression of GATA-3 and FOXP3 in the placebo group. A significant and insignificant decrease in the gene expression of T-bet and ROR- γt was detected in the OA patients who received a placebo. GATA-3 is known as a unique transcription factor for the differentiation of T-cells to the Th2 subset. The significant increase in the gene expression of GATA-3 in the patients with OA treated with crocin may suggest the beneficial effect of crocin on shifting towards the Th2 subset and enhancing an anti-inflammatory condition.

Allogeneic adipose-derived mesenchymal stromal cell transplantation for refractory lupus nephritis: Results of a phase I clinical trial.

BACKGROUND: Mesenchymal stromal/stem cells (MSCs) are known for their immunomodulatory properties. This study was performed to analyse the effects of MSC transplantation on treatment-resistant lupus nephritis (LN). METHODS: In this phase I trial, nine biopsy-proven LN patients refractory to standard treatments underwent systemic infusion of 2 × 106 allogeneic adipose-derived (AD) MSCs/kg and were followed for 12 months post-intervention. RESULTS: The treatment protocol resulted in no major adverse events. Urine protein levels significantly decreased during the first month post-intervention (baseline vs. month 1 (median): 1800 vs. 1020, P = 0.008), followed by a gradual increase but remained significantly lower than baseline only up to the 3rd month. During the first 3 months post-intervention, complete renal response (proteinuria < 0.5 g/24 h) and partial response (proteinuria > 0.5 g/24 h, but > 50% decrease in proteinuria) were observed in 33.3% and 44.4% of the patients, respectively, though these rates declined thereafter. Median score of Systemic Lupus Erythematosus Disease Activity Index decreased significantly from 16 at the baseline to 6 at sixth months post-treatment (P = 0.007), though it slightly increased at the 12th month follow-up. CONCLUSIONS: Allogenic AD-MSC transplantation was associated with favourable safety and efficient to reduce urine protein excretion and disease activity; however, the maximum effect (greatest improvement in outcomes) was observed at 1 month based on the proteinuria, and 6 months post-intervention based on disease activity scores. A single dose of AD-MSCs may not be adequate to maintain long-term remission of refractory LN, and so, additional doses may be required.

Comparative Analysis of the Effectiveness of Intra-Articular Injection of Platelet-Rich Plasma versus Hyaluronic Acid for Knee Osteoarthritis: Results of an Open-Label Trial.

BACKGROUND: Platelet-rich plasma (PRP), an autologous source of growth factors, and hyaluronic acid (HA) are among the minimally invasive treatments for knee osteoarthritis (OA). This trial was designed to compare the effectiveness of intra-articular injection of PRP with HA (as one of the standard treatments) on mild to moderate knee OA. METHODS: In this phase I open-label clinical trial, 10 patients underwent intra-articular PRP injection and 10 others received HA injection. At baseline (pre-injection) visit and 1, 3, 6, and 12 months post-injection, clinical assessments were performed using visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Physical examinations of the knee, including crepitation and range of motion (ROM) were performed at each visit. The follow-up responses were compared with the baseline visit. RESULTS: The PRP treatment was ascertained to be safe and caused no adverse effects. Significant improvements in the majority of KOOS subscales and VAS were found throughout the entire 12-month follow-up, following the PRP injections. HA injection, however, caused only one month significant improvement in the majority of patient-reported outcomes. In the majority of visits, the extent of improvements in the scores of KOOS subscales, as well as the extent of reduction in VAS were significantly greater in PRP recipients, compared to HA recipients. The ROM in both groups slightly increased after interventions. The frequency of coarse crepitation, which was detected in 100% of the patients in both groups at the baseline visit, decreased significantly to fine crepitation at the first follow-up visit in 80% and 40% of the PRP and HA recipients, respectively. CONCLUSION: Intra-articular injection of PRP or HA alleviates symptoms and pain and improves functionality and physical examinations in patients with knee OA. However, PRP therapy produces greater and longer-lasting improvements in most of the outcome parameters compared to HA.

Serum B cell activating factor (BAFF) and sarcoidosis activity.

OBJECTIVES: This study aims to determine the relationship between the severity of sarcoidosis and serum B-cell activating factor (BAFF) concentrations. PATIENTS AND METHODS: This cross-sectional study was conducted between December 2015 and March 2018 on 55 patients with sarcoidosis (16 males, 39 females; mean age, 39.9; range 25 to 60 years) and 28 healthy subjects (7 males, 20 females; mean age, 39; range 25 to 60 years). The sarcoidosis patients were divided into active chronic sarcoidosis and acute sarcoidosis groups. The diagnosis of sarcoidosis was based on clinical, radiological, and pathologic findings. Also, the diagnosis of the active disease was based on the level of angiotensin-converting enzyme, active skin, eye, and lung lesions. Scadding score was also measured, and other patient information was collected by pre-designed questionnaires. RESULTS: The most involved organs were the skin (92.7%) and joints (92.3%), respectively. The mean BAFF concentration in both active chronic sarcoidosis (p=0.001) and acute sarcoidosis (p=0.001) groups was significantly higher than the control group, but the mean level of BAFF in these two groups was not significantly different (p=0.351). Between two groups of patients, only calcium (p=0.001) and forced vital capacity (p=0.021) were higher in the acute group of sarcoidosis. Also, among the factors associated with active chronic sarcoidosis and acute sarcoidosis, none was significantly correlated with BAFF. CONCLUSION: Serum BAFF concentration was higher in patients with sarcoidosis, while this was not significantly different from increasing severity of symptoms. There was no significant difference in BAFF levels between acute sarcoidosis and active chronic types.

The Correlation between Helicobacter Pylori Infection and Disease Severity in Patients with Systemic Sclerosis.

BACKGROUND Systemic sclerosis (SSc) is a relatively common connective tissue disease, which is characterized by inflammation, progressive skin fibrosis, and injuries of small vessels, particularly in the lung and kidney. It seems that Helicobacter pylori (H. pylori) might contribute to the development of SSc as an extra-gastrointestinal autoimmune disease. We investigated the association between H. pylori infections and disease severity in patients with SSc. METHODS This is a cross-sectional study. Sampling method in this study was census method in such a way that all patients with SSc referred to Imam Reza Education and Research University Medical Center from May 2015 to August 2016 were included in the study. Finally, 74 patients were selected based on the inclusion criteria. Inclusion criteria were: 1. Definitive SSc based on American College of Rheumatology/ European League Against Rheumatism 2010 (ACR/EULAR) classification for scleroderma, which was diagnosed within the last two years. 2. Not taking any proton pump inhibitors. 3. Not taking any H. pylori treatment with a standard regimen within the recent 2 months. Disease severity was assessed and determined by two rheumatologists based on the Medsger's Disease Severity Scale (MDSS). H. pylori stool antigen was evaluated based on the test which sensitivity and specificity was proven. All obtained data were statistically analyzed by SPSS 16 using Fisher's exact test Spearman correlation test (RSpearman). RESULTS Forty one (55.4%) of the 74 patients had positive stool antigens. We found a significant positive association between the severity of disease based on MDSS and titer of H. pylori stool antigen (p ≤ 0.001). CONCLUSION This study reveals that H. pylori infection may play a significant role in the severity of organ involvement in SSc.

Immunoregulatory Effects of Krocina™, a Herbal Medicine Made of Crocin, on Osteoarthritis Patients: A Successful Clinical Trial in Iran.

Osteoarthritis (OA) is the major cause of joint pain and disability. This research was planned to examine the effects of Krocina™, aherbal medicine made of crocin, an ingredient of saffron, in patients with OA. Forty patients suffering from OA were enrolled in our study and randomly divided into two groups, receiving Krocina™ and placebo, and the clinical trial continued for four months.Peripheral blood was taken from all patients and the percentage ofvarious subsets of T cells in addition to the levels of forkhead box protein P3 (FOXP3) and interleukin (IL)-17 were measured by flow cytometry technique. The visualan alog scale (VAS) index analysis decreased significantly in both groups (krocinaTM and placebo) (p<0.05). Assessment of the C-reactive protein (CRP) level in serum showed a significant decrease in the krocinaTM group (p<0.05). Moreover, we found a meaningful increase in the percentage of regulatory T cells (Tregs)cellin samples gathered from Krocina™ group (P=0.02) patients. The mean percentages of T helper (Th) 17 cellsinthe Krocina™ group and CD8+ T cellsin the placebo group patients were also meaningfully reduced (p<0.05). The geometric mean fluorescence intensity (GMFI) for IL-17 showed a significant decrease and increase in Krocina™ and placebo groups, respectively (p<0.05). No noticeable difference was observed in the percentages of Th cells and GMFI-FOXP3 in either group. Treg/Th17 ratio was shifted towards Tregscell in Krocina™ group at the end of the intervention. It is concluded that Krocina™ has immunoregulatory effects on patients with OA, ameliorating the disease.

Crocus Sativus (Saffron): An Immunoregulatory Factor in the Autoimmune and Non-autoimmune Diseases.

It has been reported that patients with arthritis, osteoarthritis, atherosclerosis, coronary artery disease, brain ischemia, diabetes, and inflammatory bowel disease (IBD) suffer from pro-inflammatory and oxidant related responses. Therefore, anti-inflammatory and anti-oxidant therapies are used to improve the quality of life of the patients. Saffron is a herbal drug that has immunomodulatory and antioxidant properties. Hence, Saffron and its components have been proposed as therapeutic agents for the treatment of the diseases. Therefore, this review article was designed to collect recent information regarding the effects of saffron and its components on the amelioration of the inflammatory symptoms in the autoimmune and non-autoimmune diseases and anti-cancerous effects from 1999 up to now via searching the Pubmed, Google Scholar, and Scopus databases. Due to fact that several investigations have reviewed the roles played by Saffron on autoimmune and non-autoimmune diseases such as multiple sclerosis, mood disorders, and Alzheimer's disease, this review article focuses on other diseases to keep the novelty of the present review for readers.

Significant immunomodulatory properties of curcumin in patients with osteoarthritis; a successful clinical trial in Iran.

Osteoarthritis (OA) routinely is known as a multifactorial degenerative joint disease. This trial aimed to assess the curcumin (an active element of turmeric) effects on the immune responses in OA patients. Thirty patients were selected according to the American College of Rheumatology (ACR) criteria and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and equally divided into the two groups; intervention (received Sinacurcumin® 80 mg daily) and placebo, followed for 3 months. In the intervention group, our data showed a noticeably decrease in Visual Analog Score (VAS), C-reactive protein (CRP), CD4+ and CD8+ T cells, Th17 cells and B cells frequency. Additionally, Treg cells indicated a significant increase and Treg/Th17 cells ratio showed a meaningfully shifted toward Treg lymphocytes. In conclusion, our data indicated that clinical manifestation was ameliorated considerably following the administration of curcumin. Moreover, our data demonstrated the immunomodulatory effects of curcumin in OA patients.

The Sufficient Immunoregulatory Effect of Autologous Bone Marrow-Derived Mesenchymal Stem Cell Transplantation on Regulatory T Cells in Patients with Refractory Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an advanced autoimmune disease described by joint involvement. The special properties of mesenchymal stem cells (MSCs) introduced them as a potential therapeutic candidate for RA. In this study, a single dose of autologous MSCs isolated from bone marrow (autologous BM-MSCs, 1 × 106 per kg) was injected intravenously into 13 patients suffering from refractory RA who were followed up within 12 months after the intervention to evaluate immunological elements. Our results showed that the gene expression of forkhead box P3 (FOXP3) in peripheral blood mononuclear cells (PBMCs) considerably increased at month 12. We found a substantial increasing trend in the culture supernatant levels of IL-10 and transforming growth factor-beta 1 (TGF-ß1) in PBMCs from the beginning of the intervention up to the end. Our data may reflect the sufficient immunoregulatory effect of autologous BM-MSCs on regulatory T cells in patients suffering from refractory RA.

A significant decrease of BAFF, APRIL, and BAFF receptors following mesenchymal stem cell transplantation in patients with refractory rheumatoid arthritis.

In the present study, we aimed to evaluate effects of autologous mesenchymal stem cells (MSCs) intravenous administration on the response of B cells, BAFF, APRIL, and their receptors on the surface of B cells at 1, 6, and 12 month follow-up periods in refractory rheumatoid arthritis (RA) patients. Thirteen patients with refractory RA received autologous MSCs. Plasma levels of BAFF and APRIL were measured employing ELISA method, followed by estimating B cell population and BAFFRs evaluation by flow cytometry technique. Gene expression of BAFF, APRIL, and their receptors on B cell surface in PBMCs was evaluated by SYBR Green real-time PCR technique. Plasma concentration of BAFF significantly decreased 1 and 6 months after the MSCT (MSCs Transplantation). Plasma concentration of APRIL significantly decreased 1 month after the MSCT. Percentages of CD19 + B cells in the PBMC population significantly decreased 12 months after the MSCT. Percentages of BR3 + CD19 + B cells and BCMA + CD19 + B cells significantly decreased at the 12th month after the MSCT. The gene expression of BAFF in the PBMC population significantly decreased during 6, and 12 months after the MSCT. The gene expression of APRIL significantly decreased on month 6 after the MSCT. The gene expression of BR3 significantly decreased during 1, 6, and 12 months after the MSCT. The MSCT seems to decrease B cells response because of the reduced production of BAFF and APRIL cytokines and decrease the expression of their receptors on the surface of B cells.

Intravenous injection of autologous bone marrow-derived mesenchymal stem cells on the gene expression and plasma level of CCL5 in refractory rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is the most prevalent autoimmune disease, in which CCL2 and CCL5 are critically involved. The objective was to evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells (MSCs) on the foregoing chemokines in RA patients. MATERIALS AND METHODS: Thirteen RA patients were evaluated in terms of clinical manifestations, paraclinical factors, gene expression, and plasma levels of CCL2 and CCL5 prior to treatment and 1 and 6 months after intervention. Real-time-polymerase chain reaction and enzyme-linked immunosorbent assay were employed to assess the gene expression and plasma levels of CCL2 and CCL5 at different time points after MSC therapy. Statistical analysis was performed by SPSS 16 and Prism 7. RESULTS: The CCL2 gene expression had statistically significantly increased (P = 0.034), and its plasma level had insignificantly reduced after 1 month. Furthermore, the gene expression and plasma level of CCL5 had statistically significantly decreased (P = 0.032, P < 0.001). The CCL5 gene expression had statistically significantly increased after 6 months (P = 0.001) and its plasma level had insignificantly reduced. CONCLUSION: The most significant inhibitory effects of MSC therapy on the gene expression and plasma level of CCL5 were observed at the end of 1 month. The differences between the gene expression and protein levels during the treatment might be related to microRNA effects or the insufficient number of MSC injection.

MicroRNAs as the Important Regulators of T Helper 17 Cells: A Narrative Review.

T helper (Th)-17 cells are a distinct and important subset of Th cells and their functions are due to the ability of production and secretion of key cytokines in the immune system such as interleukin (IL)-17, IL-22, IL-21, and tumor necrosis factor-α (TNF-α). According to these cytokines, these cells have vital roles in the pathogenesis of the disease such as rheumatoid arthritis (RA) and osteoarthritis (OA). Nowadays, microRNAs (miRNAs) are defined as essential regulators of cell function by targeting transcription factors and other elements that act in cells to control gene expression. The purpose of this study was to detect and investigate articles evaluating the function of miRNA in Th-17 cell performance. The language was restricted to English and the search was done in PubMed, Web of Science and Embase. In this review, we first explain the role of effective factors in the function of Th17 lymphocytes, and then, we summarize the performance of several miRNAs involved in the activation and appropriate functions of Th17 cells in the immune system.

The role of BAFF and APRIL in rheumatoid arthritis.

Development and activation of B cells quickly became clear after identifying new ligands and receptors in the tumor necrosis factor superfamily. B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are the members of membrane proteins Type 2 family released by proteolytic cleavage of furin to form active, soluble homotrimers. Except for B cells, ligands are expressed by all such immune cells like T cells, dendritic cells, monocytes, and macrophages. BAFF and APRIL have two common receptors, namely TNFR homolog transmembrane activator and Ca2+ modulator and CAML interactor (TACI) and B cell-maturation antigen. BAFF alone can also be coupled with a third receptor called BAFFR (also called BR3 or BLyS Receptor). These receptors are often expressed by immune cells in the B-cell lineage. The binding of BAFF or APRIL to their receptors supports B cells differentiation and proliferation, immunoglobulin production and the upregulation of B cell-effector molecules expression. It is possible that the overexpression of BAFF and APRIL contributes to the pathogenesis of autoimmune diseases. In BAFF transgenic mice, there is a pseudo-autoimmune manifestation, which is associated with an increase in B-lymphocytes, hyperglobulinemia, anti-single stranded DNA, and anti-double-stranded DNA antibodies, and immune complexes in their peripheral blood. Furthermore, overexpressing BAFF augments the number of peripheral B220+ B cells with a normal proliferation rate, high levels of Bcl2, and prolonged survival and hyperactivity. Therefore, in this review article, we studied BAFF and APRIL as important mediators in B-cell and discussed their role in rheumatoid arthritis.

Amelioration of clinical symptoms of patients with refractory rheumatoid arthritis following treatment with autologous bone marrow-derived mesenchymal stem cells: A successful clinical trial in Iran.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune arthropathy characterized by synovial hyperplasia leading to functional impairment. Although the exact cause of RA is unknown, there is evidence suggesting the role of T cell subtypes in the pathogenesis of RA. Conventional therapy in some RA patients is associated with mild or severe side effects, and resistance of some patients has been reported to these types of therapy. The therapeutic potential of mesenchymal stem cells (MSCs) introduced them as a novel therapeutic choice for the treatment of rheumatic diseases. The aim of our study was to evaluate the effects of intravenous administration of autologous bone marrow-derived MSCs on the immunological, clinical and para-clinical factors such as regulatory T cells, Th17 cells, CD8+ T cells, CD4+ T cells, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), visual analogue scale (VAS), ESR, C-reactive protein (CRP), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibodies in patients with refractory RA. Nine refractory RA patients with no other rheumatologic disorders were included in this study. All patients received a single intravenous dose of 1 × 106 autologous bone marrow-derived MSCs/kg, and were followed up at 1, 6 and 12 months after injection of MSCs. We found a significant decreasing trend in Th17 percentage and geometric mean fluorescence intensity for IL-17A following injection of MSCs at 12 months compared to the time point zero. Furthermore, a significant increase in regulatory T cells percentage was observed at the end of the first month after the intervention. DAS28-ESR decreased significantly at 1 and 12 months after MSC therapy. VAS score showed a significant decreasing trend during the follow-up periods. No significant difference was found for serum CRP and anti-CCP levels after the intervention. In conclusion, our data indicated that clinical symptoms were significantly ameliorated following the intravenous injection of autologous bone marrow-derived MSCs to the patients with refractory RA.