Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
32030116 Real-World Dose Modification Patterns of Subcutaneous Tocilizumab Among Patients with Rheu 2019 Dec BACKGROUND: The treatment of rheumatoid arthritis is based on the use of disease-modifying antirheumatic drugs (DMARDs). Tocilizumab can be used as monotherapy or in combination with conventional synthetic DMARDs for the treatment of moderate-to-severe active rheumatoid arthritis. Subcutaneous (SC) and intravenous forms of the drug are available, but the SC form is more widely used. OBJECTIVE: To understand the real-world dose modification patterns of SC tocilizumab in the treatment of patients with rheumatoid arthritis in the United States. METHODS: Data were obtained from the Truven (now IBM) MarketScan and Optum Clinformatics databases. Patients were included if they had ≥1 pharmacy claims for SC tocilizumab and met other inclusion criteria. The mean, standard deviation, and median values were reported for the continuous variables, and frequency was reported for the categorical variables. Kaplan-Meier analysis was used to analyze the time to first dose modification. Logistic regression modeling was used to identify predictors of the likelihood of dose modification. RESULTS: The study included 1266 patients in the Truven database and 512 patients in the Optum database who had commercial or Medicare Advantage or supplemental insurance. Of the patients who started treatment with biweekly SC tocilizumab (48% each in the Truven and Optum databases), 37% in Truven and 40% in Optum had dose escalation to a weekly dose. Of those who started weekly SC tocilizumab (43% in the Truven and 49% in the Optum databases), 3% (Truven) and 4% (Optum) had dose reduction. The remaining patients started alternative SC tocilizumab doses. Overall, 60% and 68% of patients in the Truven and Optum cohorts, respectively, initiated or escalated to the higher weekly dose of tocilizumab; the mean time to dose escalation was 126 days and 112 days, respectively. In the Truven cohort, corticosteroid use, age, and anemia were the main predictors for dose escalation. In the Optum cohort, female patients had increased odds of dose escalation compared with male patients. CONCLUSION: The dosing trends observed in this study show that physicians have taken advantage of the option to increase SC tocilizumab dosing, but only a few providers chose to reduce the dose. This trend in dose modification may increase the costs related to SC tocilizumab therapy.
31261785 Current Therapeutic Options in the Treatment of Rheumatoid Arthritis. 2019 Jun 28 Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints. Untreated RA leads to a destruction of joints through the erosion of cartilage and bone. The loss of physical function is the consequence. Early treatment is important to control disease activity and to prevent joint destruction. Nowadays, different classes of drugs with different modes of action are available to control the inflammation and to achieve remission. In this review, we want to discuss differences and similarities of these different drugs.
33281390 Therapeutic influence of some dietary articles on gut microbiota in the pathogenesis of rh 2019 Jul BACKGROUND: Amavata is a chronic immune‑inflammatory systemic disorder caused by the formation of Ama and its association with Vata at Kaphasthana (joints) and can be simulated with rheumatoid arthritis (RA). Published evidences show that treatment indicated in Amavata is effective in RA. Increased inflammatory status in RA is suggestive of gut dysbiosis involving gut microbiota (GM). AIM: The aim of the present study was to analyze the influence of diet on GM of RA patients based on Pathya (dietary advice) mentioned for Amavata. MATERIALS AND METHODS: Laghutrayis such as Bhavaprakasha Samhita, Madhava Nidana and Sharangadhara Samhita, Bhaishajya Ratnavali and Nighantus (Sanskrit glossary) such as Raja Nighantu, Bhavaprakasha Nighantu and Yogaratnakara, Ashtanga Hridaya also different databases were reviewed for Pathya of Amavata. Different databases such as PubMed, Scopus, DHARA, Google Scholar, Science Direct were searched with research papers establishing the role of nonnutritive bioactive components in horse gram, barley, garlic, ginger, drumstick leaves, cow urine and buttermilk in the management of RA were also reviewed. It was found that Pathya influences on the GM by lowering or inhibiting inflammatory markers such as interleukin‑6 (IL‑6), 17 and leukotrines through Bowman‑Birk inhibitors and polyphenolic compounds. Among them, Takra is already a proven probiotic. Gomutra augments B and T lymphocytes, IL‑1 and IL‑2, strengthening the immune system. CONCLUSION: It was concluded that Pathya Ahara mentioned for Amavata have a direct link with GM of RA patients. Even though the pharmacological actions have been clinically proven/practised, this review creates evidence for its scientific basis.
31217874 Bcl2 like protein-12 suppresses Foxp3(+) regulatory T cells in patients with rheumatoid ar 2019 Immune dysregulation plays an important role in the pathogenesis of rheumatoid arthritis (RA). Bcl2 like protein 12 (Bcl2L12) has the ability of immune regulation. This study aims to investigate the role of Bcl2L12 in interfering with Foxp3(+) regulatory T cell (Treg) development and function in RA patients. In this study, RA patients were recruited in RA clinic. The peripheral blood samples were collected from RA patients and healthy (HA) subjects. Treg status was analyzed by a variety of immune assessing approaches. We observed that the frequency of Tregs in RA patients was significantly lower than that in HA subjects. The expression of Bcl2L12 was detected in CD4(+) T cells, which was markedly higher in the RA group than that in HA group. Naive CD4(+) T cells from RA patients were refractory to develop as Tregs. Inhibition of Bcl2L12 in CD4(+) T cells from RA patients promoted Treg generation. Tregs isolated from RA patients showed functional defects, which could be restored by knocking down of Bcl2L12. In conclusion, Bcl2L12 plays a role in suppressing Treg development and function in RA patients. Inhibition of Bcl2L12 may have therapeutic potential in the treatment of RA.
30693283 IL-17 in Rheumatoid Arthritis and Precision Medicine: From Synovitis Expression to Circula 2018 Interleukin (IL)-17A has a direct contribution in early induction and late chronic stages of various inflammatory diseases. In vitro and in vivo experiments have first characterized its local effects on different cell types and then its systemic effects. For instance, IL-17 axis is now identified as a key driver of psoriasis through its effects on keratinocytes. Similar observations apply for rheumatoid arthritis (RA) where IL-17A triggers changes in the synovium that lead to synovitis and maintain local inflammation. These results have prompted the development of biologics to target this cytokine. However, while convincing studies are reported on the efficacy of IL-17 inhibitors in psoriasis, there are conflicting results in RA. Patient heterogeneity but also the involvement of mediators that regulate IL-17 function may explain these results. Therefore, new tools and concepts are required to identify patients that could benefit from these IL-17 targeted therapies in RA and the development of predictive biomarkers of response has started with the emergence of various bioassays. Current strategies are also focusing on synovial biopsies that may be used to stratify patients. From local to systemic levels, new approaches are developing and move the field of RA management into the era of precision medicine.
31766446 Interstitial Lung Disease in Rheumatoid Arthritis Remains a Challenge for Clinicians. 2019 Nov 21 Interstitial lung disease (ILD) is a serious complication of rheumatoid arthritis (RA) contributing to significantly increased morbidity and mortality. Other respiratory complications, such as chronic obstructive pulmonary disease and bronchiectasis, are frequent in RA. Infections and drug toxicity are important differential diagnoses and should be considered in the diagnostic work-up of patients with RA presenting with respiratory symptoms. This review provides an overview of the epidemiology and pathogenesis of RA-ILD, the radiological and histopathological characteristics of the disease as well as the current and future treatment options. Currently, there is no available evidence-based therapy for RA-ILD, and immunosuppressants are the mainstay of therapy. Ongoing studies are exploring the role of antifibrotic therapy in patients with progressive fibrotic ILD, which may lead to a new treatment approach for subgroups of patients with RA-ILD.
31431810 The role of microbiome in rheumatoid arthritis treatment. 2019 Rheumatoid arthritis (RA) is an autoimmune disorder with multifactorial etiology; both genetic and environmental factors are known to be involved in pathogenesis. Treatment with disease-modifying antirheumatic drugs (DMARDs) plays an essential role in controlling disease progression and symptoms. DMARDs have immunomodulatory properties and suppress immune response by interfering in various pro-inflammatory pathways. Recent evidence has shown that the gut microbiota directly and indirectly modulates the host immune system. RA has been associated with dysbiosis of the gut microbiota. Patients with RA treated with DMARDs show partial restoration of eubiotic gut microbiome. Hence, it is essential to understand the impact of DMARDs on the microbial composition and its consequent influences on the host immune system to identify novel therapies for RA. In this review, we discuss the importance of antirheumatic-drug-induced host microbiota modulations and possible probiotics that can generate eubiosis.
31239737 Abatacept: from a budget impact model to cost-effectiveness analysis - data from RCT and r 2019 Rheumatoid arthritis (RA) is a chronic inflammatory disorder that affects joints with swelling and progressive joint destruction. The pathology leads to a progressive disability with an impact on the quality of life of the patients. Strategies to reduce in-patient care costs could have a considerable impact on lowering the direct medical costs of RA in Italy. Abatacept, a selective T-cell costimulation modulator, is a valuable treatment option for patients with moderate-to-severe RA. A search using the keywords "cost-effectiveness analysis", "budget impact model", "abatacept", and "rheumatoid arthritis" was carried out on PubMed. Abatacept in the first- and second-treatment lines has been evaluated in our research. We evaluated patients with inadequate MTX response, inadequate anti-TNF agents response, switch studies and real-world data. Furthermore, in our research, we evaluated the main head-to-head studies published.
32280660 The effect of ginger supplementation on IL2, TNFα, and IL1β cytokines gene expression le 2019 Background: Rheumatoid arthritis (RA) is a chronic autoimmune and inflammatory disease that affects the joints and consequently leads to the destruction of cartilage and bone lesions. Traditionally, ginger has been consumed in treatment of osteoarthritis, joint and muscle pain, neurological diseases, and inflammation of gums, tooth pain, asthma, stroke, diabetes, and constipation. The aim of this study was to determine the effect of ginger on some immunological and inflammatory markers in patients with rheumatoid arthritis. Methods: In this study, which was performed during 2013-2016, 66 patients with active rheumatoid arthritis who referred to the rheumatology clinic at Shariati hospital were en-rolled. Patients were randomly divided into 2 groups: one group consumed 1.5 gr ginger per day, and the other group took roasted wheat flour (placebo), respectively. To determine the effect of confounding factors on the findings of the study, questionnaires for nutrient intake, physical activity, and medication were filled, and BMI was measured. For each participant, at the beginning and end of the study, Serum hs-CRP and mRNA levels of IL-1β, IL-2 and TNF-α were determined by ELISA and Quantitative Real Time PCR, respectively. Statistical analysis was performed using SPSS software. Significance level was set at p<0.05. Results: Results of the study showed ginger powder supplementation caused a significant decline in CRP (p=0.050) and IL-1β mRNA level (p=0.021). TNFα mRNA levels reduced in ginger group compared to placebo groupalthough the difference was not significant between the 2 groups (p=0.093). Ginger had no effects on IL2 gene expression. Conclusion: This study showed that ginger reduces inflammatory factors hs-CRP and IL-1β gene expression in patients with active RA and it seems that ginger can improve the inflam-mation in the patients.
30937527 [Sjögren's syndrome]. 2019 Aug The prevalence of primary Sjögren's syndrome (pSS) is between 1:100 and 1:1000 and it is therefore the most common connective tissue disease. Nevertheless, it can be difficult to diagnose pSS as the symptoms are frequently unspecific and diagnostic markers are lacking in many patients. In addition, only few controlled therapeutic studies of pSS have been carried out so that the optimal management is not yet clear. Meanwhile, outcome parameters to monitor clinical improvement have been developed and a large number of therapeutic studies are currently being performed. This review article summarizes the current diagnostic and treatment options for pSS.
32038727 Receptor targeting drug delivery strategies and prospects in the treatment of rheumatoid a 2019 Dec Rheumatoid arthritis (RA), a chronic inflammatory disease, is characterized by cartilage damage, bone tissue destruction, morphological changes in synovial fluids, and synovial joint inflammation. The inflamed synovial tissue has potential for passive and active targeting because of enhanced permeability and retention effect and the existence of RA synovial macrophages and fibroblasts that selectively express surface receptors such as folate receptor β, CD44 and integrin αVβ. Although there are numerous interventions in RA treatment, they are not safe and effective. Therefore, it is important to develop new drug or drug delivery systems that specifically targets inflamed/swollen joints but attenuates other possible damages to healthy tissues. Recently some receptors such as toll-like receptors (TLRs), the nucleotide-binding oligomerization domain-like receptors, and Fc-γ receptor have been identified in synovial tissue and immune cells that are involved in induction or suppression of arthritis. Analysis of the TLR pathway has moreover suggested new insights into the pathogenesis of RA. In the present paper, we have reviewed drug delivery strategies based on receptor targeting with novel ligand-anchored carriers exploiting CD44, folate and integrin αVβ as well as TLRs expressed on synovial monocytes and macrophages and antigen presenting cells, for possible active targeting in RA. TLRs could not only open a new horizon for developing new drugs but also their antagonists or humanized monoclonal antibodies that block TLRS specially TLR4 and TLR9 signaling could be used as targeting agents to antigen presenting cells and dendritic cells. As a conclusion, common conventional receptors and multifunctional ligands that arte involved in targeting receptors or developing nanocarriers with appropriate ligands for TLRs can provide profoundly targeting drug delivery systems for the effective treatment of RA.
31137469 Application of GC/MS-Based Metabonomic Profiling in Studying the Therapeutic Effects of Ac 2019 May 20 Aconitum carmichaeli with Ampelopsis japonica (AA) is a classical traditional Chinese medicine (TCM) formula. There are a lot of examples showing that AA can be used to treat rheumatoid arthritis, but its mechanism of action is still not completely clear. In this research, collagen-induced arthritis (CIA) was chosen as a rheumatoid arthritis (RA) model. Rats of treated groups were continuously administered Aconitum carmichaeli (AC), Ampelopsis japonica (AJ) and Aconitum carmichaeli + Ampelopsis japonica (AA) orally once a day from the day after the onset of arthritis (day 7) until day 42. The results showed that AA not only significantly reduced paw swelling, but also improved the levels of TNF-α and IL-6 in serum. GC-MS-based urine metabonomics was established to analysis metabolic profiles and 21 biomarkers of RA rats were identified by the Partial Least Squares Discriminant Analysis (PLS-DA) and Support Vector Machine (SVM) methods. The prediction rate of the SVM method for the 21 biomarkers was 100%. Twenty of 21 biomarkers, including D-galactose, inositol and glycerol, gradually returned to normal levels after administration of AA. Metabolomic Pathway Analysis (MetPA) generated three related metabolic pathways-galactose metabolism, glycerolipid metabolism and inositol phosphate metabolism-which explain the mechanism of AA treatment of rheumatoid arthritis. This research provides a better understanding of the therapeutic effects and possible therapeutic mechanism of action of a complex TCM (AA) on rheumatoid arthritis.
31049128 Redox Status and Muscle Pathology in Rheumatoid Arthritis: Insights from Various Rat Hindl 2019 Due to atrophy, muscle weakness is a common occurrence in rheumatoid arthritis (RA). The majority of human studies are conducted on the vastus lateralis muscle-a muscle with mixed fiber type-but little comparative data between multiple muscles in either rodent or human models are available. The current study therefore assessed both muscle ultrastructure and selected redox indicators across various muscles in a model of collagen-induced rheumatoid arthritis in female Sprague-Dawley rats. Only three muscles, the gastrocnemius, extensor digitorum longus (EDL), and soleus, had lower muscle mass (38%, 27%, and 25% loss of muscle mass, respectively; all at least P < 0.01), while the vastus lateralis muscle mass was increased by 35% (P < 0.01) in RA animals when compared to non-RA controls. However, all four muscles exhibited signs of deterioration indicative of rheumatoid cachexia. Cross-sectional area was similarly reduced in gastrocnemius, EDL, and soleus (60%, 58%, and 64%, respectively; all P < 0.001), but vastus lateralis (22% smaller, P < 0.05) was less affected, while collagen deposition was significantly increased in muscles. This pathology was associated with significant increases in tissue levels of reactive oxygen species (ROS) in all muscles except the vastus lateralis, while only the gastrocnemius had significantly increased levels of lipid peroxidation (TBARS) and antioxidant activity (FRAP). Current data illustrates the differential responses of different skeletal muscles of the hindlimb to a chronic inflammatory challenge both in terms of redox changes and resistance to cachexia.
31428318 Content analysis of Twitter in relation to biological treatments for chronic inflammatory 2019 May OBJECTIVE: To analyse the volume and content of tweets in relation to biological treatments for chronic inflammatory arthropathies. METHODS: A Twitter analysis was carried out during one month using the following keywords: 'rheumatoid arthritis', 'ankylosing spondylitis', 'psoriatic arthritis' and their biological therapies: 'abatacept', 'adalimumab', 'certolizumab', 'etanercept', 'golimumab', 'infliximab' and 'tocilizumab'. Tweets were hand-coded and filtered for content. RESULTS: 25 441 tweets contained at least one of the keywords. After filtering, 2480 tweets were included in the analysis. Regarding the 983 tweets about therapies, the most frequently mentioned biologics were 'adalimumab' (n=359), 'infliximab' (n= 278) and 'etanercept' (n= 205). In the 1497 tweets about diseases, the term 'rheumatoid arthritis' (n= 1109) was used more frequently than 'psoriatic arthritis' (n= 233) and 'ankylosing spondylitis' (n= 155). The most commonly addressed subjects in the tweets in relation to biological therapies were related to safety/adverse events (136 of 983 (13.8%)) and to administration, particularly drug infusion (60 of 983 (6.1%)) and self-administration (57 of 983 (5.8%)). Regarding diseases, the most commonly addressed subjects were non-pharmacological recommendations such as alternative therapies (145 of 1497 (9.7%)), nutrition (128 of 1497 (8.5%)) and exercise (91 of 1497 (6.1%)). CONCLUSIONS: Twitter is widely used to search for information about biological treatments for chronic athropathies. Learning more about the subjects dealt with in the tweets will enable us to improve our understanding of the areas of greater interest and concern among patients. This could help hospital pharmacists establish patient-focused strategies addressing the needs of the patients.
30873111 Rheumatoid Meningitis Presenting With Acute Parkinsonism and Protracted Non-convulsive Sei 2019 Rheumatoid meningitis is a rare complication of rheumatoid arthritis (RA). It is associated with substantial morbidity and mortality. The condition may present in a variety of ways and is therefore diagnostically challenging. Uncertainty still exists regarding the optimal treatment strategy. Herein, we describe the case of a 74-year-old man with a history of well-controlled seropositive RA on low-dose prednisone, hydroxychloroquine, and methotrexate. The patient presented with a several-month history of multiple prolonged episodes of expressive aphasia, right hemiparesis, and encephalopathy. Although no epileptiform activity was recorded on repeated electroencephalography, the symptoms fully resolved following treatment with antiepileptic drugs. He subsequently developed acute asymmetrical parkinsonism of the right hemibody. Magnetic resonance imaging revealed subtle enhancement of the leptomeninges over the left frontoparietal convexity. Cerebrospinal fluid analysis revealed a mild lymphocytic pleocytosis and elevated proteins. Histopathologic analysis of a meningeal biopsy revealed nodular rheumatoid meningitis. The patient was treated with corticosteroids and cyclophosphamide, following which he incompletely recovered. This is the first description of rheumatoid meningitis manifesting with acute parkinsonism and protracted non-convulsive seizures. A summary of cases reported since 2005, including data on pathology, therapy and outcomes, along with a discussion on the efficacy of different treatment strategies are provided.
32010887 Serum Pyridinoline is Associated With Radiographic Joint Erosions in Rheumatoid Arthritis. 2019 Dec OBJECTIVES: This study aims to compare the serum pyridinoline (Pyd) levels between rheumatoid arthritis (RA) patients and healthy controls and to determine the correlation of serum Pyd levels with radiographic joint erosions. PATIENTS AND METHODS: Serum samples were obtained from 48 patients with RA (9 males, 39 females; mean age 60.5 years; range 54 to 64 years) and 48 healthy controls (9 males, 39 females; mean age 57.5 years; range, 47 to 65 years). The enzyme-linked immunosorbent assay method was used for quantitative analysis of serum Pyd. Besides, all RA patients were assessed for joint damage based on modified Sharp score, disease activity based on disease activity score in 28 joints and functional capacity based on health assessment questionnaire-disability index. RESULTS: The median serum Pyd levels were significantly higher among the RA patients (110.20 ng/mL [92.30-120.64]) compared to the controls (98.22 ng/mL [85.54-111.41]); p<0.05. RA patients with erosive disease had significantly higher serum Pyd levels (p=0.024). There was a significant positive correlation between serum Pyd levels and joint erosion score (r=0.285, p=0.049). The serum Pyd levels had no demonstrable association with disease activity or functional capacity. Steroid therapy did not appear to influence the levels of serum Pyd. CONCLUSION: Rheumatoid arthritis patients had significantly higher levels of serum Pyd compared to healthy controls. The serum Pyd levels had significant correlation with radiographic joint erosions which reflected disease damage.
32010898 Nitroxidized-Albumin Advanced Glycation End Product and Rheumatoid Arthritis. 2019 Dec Rheumatoid arthritis (RA) is an autoimmune disease whose major clinical consequence is inflammation of small joints and contiguous structures. Oxidative and nitrosative stress along with increased formation of advanced glycation end products (AGEs) play an important role in the disease process. Generation of reactive species during glycation of proteins further adds to the oxidative and nitrosative stress. Albumin, being the most abundant plasma protein, is frequently targeted by different oxidizing and nitrating agents, including peroxynitrite (OONO-) anion. Albumin is also targeted and modified by dicarbonyl metabolites (glyoxal and methylglyoxal) which are formed in oxidative and non-oxidative processes during the synthesis of AGEs. The endogenously formed OONO- and dicarbonyls may modify plasma albumin including those albumin that have travelled or migrated to synovial cells and caused nitration, oxidation, and glycation. These modifications may produce crosslinks, aggregate in albumin and confer immunogenicity. Simultaneous modification of albumin by OONO- and dicarbonyls may generate nitroxidized-AGE-albumin which may persist in circulation for a longer duration compared to native albumin. Nitroxidized-AGE-albumin level (or serum autoantibodies against nitroxidized- AGE-albumin) along with other pre-clinical features may help predict the likely onset of RA.
30692825 The roles of anti-citrullinated protein antibodies in the immunopathogenesis of rheumatoid 2019 Jan Rheumatoid arthritis (RA) is a common systemic autoimmune disease. Its major manifestation is persistent joint inflammation, which can lead to bone destruction and severe disability. The immunopathogenesis of RA is very complex, involving both innate and adaptive immune systems. Recently, the discovery of anti-citrullinated protein antibodies (ACPAs) has revolutionized the diagnosis and our understanding of the immunopathogenesis of RA. The presence of ACPAs is also closely linked to the disease activity of RA. Therefore, it is reasonable to believe that ACPAs and protein citrullination are key issues for the development of RA. We have summarized the recent study results in this review. The first theory concerning the pathogenesis of RA proposed that ACPAs link the well-known genetic and environmental risk factors for developing RA. However, due to the close association between joint inflammation and ACPAs, a more direct role of ACPAs in the immunopathogenesis of RA is anticipated. Within the past 10 years, many studies, including some of our own, have shown that ACPAs can promote an inflammatory response through complement activation, formation of neutrophil extracellular traps, and direct binding to key players, including monocytes, osteoclasts, and osteoblasts, in the mediation of bone destruction in the joints of RA patients. We also present some new perspectives and issues that need to be further investigated.
32140060 Etanercept in the treatment of Graves' ophthalmopathy with primary hypothyroidism and rheu 2019 Graves' ophthalmopathy (GO) is an autoimmune disease affecting ocular and orbital tissues. Overproduction of tumor necrosis factor α (TNF-α) in rheumatoid arthritis (RA) and GO has destructive consequences. The subject of this paper is a case of a female patient initially diagnosed with primary hypothyroidism substitution with levothyroxine, and subsequent diagnosis of RA with insufficient therapeutic efficacy of a standard medication. Three years later, the patient presented symptoms and signs of GO. Etanercept was administrated for RA, and after four months, an improvement of the eye symptoms and reduced exophthalmos were observed and confirmed using visual methods. Graves' ophthalmopathy association with primary hypothyroidism is uncommon. The treatment of RA using etanercept led to clinical improvement of GO symptoms, which indicates that RA and GO may share similar pathogenic features. The paper suggests that etanercept may suppress the symptoms and clinical signs of GO. However, controlled trials are needed to further evaluate the effect of TNF-α inhibitors, particularly etanercept, and to compare its side effects with the current options for medical treatment.
31655532 IFN-? stimulated dental follicle mesenchymal stem cells regulate activated lymphocyte resp 2019 Oct 27 BACKGROUND/AIM: Multipotent mesenchymal stem cells (MSCs) have been investigated in autoimmune diseases such as rheumatoid arthritis (RA) due to their immunomodulatory and regenerative properties. In this study, their immunosuppressive effects on peripheral blood mononuclear cells (PBMC) of RA patients were studied. MATERIALS AND METHODS: Dental Follicle Stem Cells (DFSCs) were isolated from follicle tissue in the orofacial region. Characterization and multipotency analyses were performed. Lymphocytes were isolated from peripheral venous blood of RA patients (n=5) and healthy individuals (n=5). DFSCs were pre-incubated with IFN-? for 48 hr. PBMCs of RA patients and healthy individuals were separately cultured with or without DFSCs for 72 hours. After the culture period, lymphocyte proliferation and viability, the frequency of CD4+ CD25+FoxP3+ T regulatory cells, IL-10 and TNF-? levels in the culture supernatants were measured via flow cytometry. RESULTS: Our results demonstrated that DFSCs suppressed proliferation of T lymphocytes by increasing the number of FoxP3 expressing CD4+CD25+ T regulatory cells and suppressed lymphocyte apoptosis in RA patients. Also, DFSCs reduced TNF-? cytokine secretion and upregulated IL-10 secreting cells. CONCLUSIONS: Such cells could potentially be a source for future immunomodulatory treatments of RA patients.