Browse

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

ID PMID Title PublicationDate abstract
26999417 IL-1β at the crossroad between rheumatoid arthritis and type 2 diabetes: may we kill two 2016 Aug Although in the past the prevention of joint destruction in rheumatoid arthritis (RA) was strongly emphasized, now a great interest is focused on associated comorbidities in these patients. Multiple data suggest that a large percentage of RA patients are affected by Type 2 Diabetes (T2D), whose incidence has reached epidemic levels in recent years, thus increasing the health care costs. A better knowledge about the pathogenesis of these diseases as well as the mechanisms of action of drugs may allow both policy designers and physicians to choose the most effective treatments, thus lowering the costs. This review will focus on the role of Interleukin (IL)-1β in the pathogenesis of both the diseases, the efficacy of IL-1 blocking molecules in controlling these diseases, and will provide information suggesting that targeting IL-1β, in patients affected by both RA and T2D, may be a promising therapeutic choice.
26208443 From the model of integral attention to the creation of centers of excellence in rheumatoi 2015 Mar For the Pan American Health Organization (PAHO), the care of patients with chronic diseases currently experiences fragmentation in attention, generating poor performance of health services. Thus, comprehensive health care strategies arise to mitigate these problems; one of them are Centers of Excellence (CoEs), which aim to obtain high quality results in health from the adequate and minimum use of resources. The objective of this study was to describe the history and current context of the CoE in comprehensive care in patients with rheumatoid arthritis (RA). A systematic search of the literature terms (MeSH) was performed. The bases used were PubMed, Ebsco Host, Lilacs, Science Direct, Ovid, and Google (gray literature). The source of the information was evaluated to determine its quality. International standards focus the CoEs starting from comprehensive management of patients with RA and patient volume, continuous improvement, and quality of health care, constituting an interdisciplinary team. The REAL-PANLAR group suggested that the inclusion of the strategy "Treat to Target", and patient education improves patient conditions and understanding of the disease. RA is a prevalent and costly disease. The creation of comprehensive care centers of the CoE type is an initiative that improves the prognosis of RA. This document aims to encourage rheumatologists and scientific societies to structure CoE in an interdisciplinary endeavor.
27013626 [Genome-wide association study for rheumatoid arthritis]. 2016 Apr Rheumatoid arthritis(RA)is a multifactorial disease, where both genetic and environmental factors are involved. Genome-wide association studies have been identified more than 100 loci associated with RA. Majority of these loci are expression quantitative trait loci(eQTLs), in which genetic variants regulate the level of transcription. Here, I review the genetic background of RA, by describing the RA-associated genes such as HLA-DRB1, PADI4, and CCR6.
26563338 Multidisciplinary team care for people with rheumatoid arthritis: a systematic review and 2016 Mar The objective of this study was to systematically review the evidence from randomised controlled trials (RCTs) evaluating the effectiveness of multidisciplinary team (MDT) care for the management of disability, disease activity and quality of life (QoL) in adults with rheumatoid arthritis (RA). Data sources identified published (MEDLINE, PsychINFO, EMBASE, CINAHL, Web of Science, CENTRAL) and unpublished (OpenGrey) literature. Independent data extraction and quality assessment, using the Cochrane risk of bias tool, were conducted by two reviewers. The primary outcome was change in disability at 12 months; secondary outcomes included disability at other time points and disease activity and QoL at 12 months. Where possible, the pooled effect sizes were calculated for inpatient or outpatient MDT interventions. Four hundred and fifteen studies were retrieved. Twelve manuscripts, which reported 10 RCTs, representing 1147 participants were included. Only data from five high- or moderate-quality trials were pooled according to clinical setting. There was no difference in disability between inpatient MDT care and any comparison group [mean difference (95% confidence intervals) 0.04, -0.13 to 0.20] or between outpatient MDT care and comparison groups (0.09, -0.07 to 0.25) at 12 months. There was no difference in disability at 2 years or <12 months or disease activity and QoL at 12 months between MDT care and any comparison group. There is limited evidence evaluating the effect of MDT care on disability, disease activity or QoL in people with RA. There is likely to be no effect of MDT care on disability at 12 months or other time points.
26609565 The effect of gene polymorphisms on patient responses to rheumatoid arthritis therapy. 2016 INTRODUCTION: Rheumatoid arthritis (RA) is a systemic disease leading to joint destruction. The therapy of RA is mainly based on disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs. The response to treatment is different among patients. Therefore, we have searched for factors that may predict the efficacy and toxicity during therapy in individual patients. AREAS COVERED: This review presents the role of genetic polymorphisms as predictors of the efficacy and toxicity during the therapy of RA patients with DMARDs (methotrexate, leflunomide, sulfasalazine) and biological drugs (anti-TNF-alpha antagonists, Tocilizumab, Rituximab). EXPERT OPINION: Despite studies having shown an association between genetic polymorphisms and response to therapy in RA patients, the majority of these findings are still inconclusive and inconsistent. We are still far from applying pharmacogenetic tests in routine clinical practice that can predict the outcome of treatment. Several factors, such as small sample size with low statistical power, variability in the outcome definitions and the heterogeneity of the cohorts, limited number of tested single nucleotide polymorphisms (SNPs), small effect for the selected variant, and a lack of consideration of epigenetic factors, may contribute to the inconsistency observed and may lead to limited success in personalizing therapy.
26692475 Risk of incident atrial fibrillation in patients with rheumatoid arthritis: a systematic r 2017 Apr AIMS: Patients with rheumatoid arthritis (RA) might be at an increased risk of developing atrial fibrillation (AF) as a result of deleterious effects of inflammatory cytokines on cardiomyocytes. This study aimed to comprehensively review all available evidence to further characterize this possible association. METHODS: We conducted a systematic review and meta-analysis of cohort studies that reported relative risk, hazard ratio, incidence ratio or standardized incidence ratio with 95% confidence intervals comparing the risk of incidence of AF in patients with RA versus non-RA participants. Pooled risk ratio and 95% confidence interval were calculated using random-effect, generic inverse-variance methods of DerSimonian and Laird. RESULTS: Three retrospective cohort studies with 39 912 cases of RA and 4 269 161 non-RA controls were included in the data analysis. The pooled risk ratio of subsequent development of AF in patients with RA versus controls was 1.29 (95% CI, 1.05-1.59). The statistical heterogeneity was moderate with an I(2) of 71%. CONCLUSION: Our meta-analysis demonstrated a statistically significant increased risk of subsequent development of AF among patients with RA.
27029468 Rheumatoid meningitis. 2016 Aug Rheumatoid meningitis is a rare, potentially treatable condition that can mimic a wide range of neurological conditions, including vascular syndromes and encephalopathies. Despite a concurrent history of rheumatoid arthritis, patients often have no active synovitis. Here we describe a patient with rheumatoid meningitis who presented to a hyperacute stroke unit with dysarthria on waking and transient facial droop.
27762192 The Computer Assisted Management in Early Rheumatoid Arthritis programme tool used in the 2016 Sep The history, issues and result of the development of the computer decision software tool used for the two tight control and treat-to-target CAMERA (Computer Assisted Management in Early Rheumatoid Arthritis) studies are described. The software tool is simple and can be used with various protocolled strategies and visit intervals both in clinical trials and daily practice, because it does not dictate strategy steps and is independent of visit intervals. The tool gives information on whether enough improvement since the last visit is present and whether there is remission or not. With this information, strategy steps according to various protocols and treatment arms can be taken.
25719499 One year in review: novelties in the treatment of rheumatoid arthritis. 2015 Jan Rheumatoid arthritis (RA) is a chronic disease characterised by inflammation of the synovial tissue in joints, which can lead to joint destruction. The primary aim of the treatment is to control pain and inflammation, reduce joint damage and disability, and maintain or improve physical function and quality of life. In this article, we provide a critical analysis of the recent literature on the novelties in the treatment of RA, with a particular focus on the most relevant studies published over the last two years.
26235544 Sustained biologic-free and drug-free remission in rheumatoid arthritis, where are we now? 2015 Aug 3 The advent of new medications and new treatment strategies for rheumatoid arthritis has made it possible to achieve remission in more patients than before. Furthermore, recent clinical trials and register studies suggest that some patients who initially required aggressive therapy may achieve biologic-free remission or even the ultimate goal of therapy, drug-free remission, resembling recovery. Here, we present a discursive review of the most important studies addressing these issues. Based on the overall results, it remains unclear if achieving biologic-free and drug-free remissions are primarily due to the natural course of the disease or to the early therapeutic intervention according to the 'window of opportunity' hypothesis. Although medication-free remission is only achievable in a small subset of patients, characterizing this patient cohort may provide important information about beneficial prognostic factors and the underlying mechanisms. In summary, in a subset of patients biologic-free and even drug-free remission can be achieved; pursuing these possibilities in practice may decrease the risk for long-term side effects and attenuate the economic burden of the disease.
27779104 TNFAIP3 gene rs10499194, rs13207033 polymorphisms decrease the risk of rheumatoid arthriti 2016 Dec 13 Accumulating evidences suggested that tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs10499194, rs13207033 polymorphisms may be associated with the risk of rheumatoid arthritis (RA). However, these studies yielded contradictory findings. To clarify convincing associations, we conducted a comprehensive meta-analysis by searching in PubMed, Embase, and the China Knowledge Resource Integrated Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. A total of 13 case-control studies for rs10499194 polymorphism and 6 studies for rs13207033 polymorphism were included. Our data indicated that TNFAIP3 gene rs10499194, rs13207033 polymorphisms were associated with the decreased risk of RA. Stratification analyses of ethnicity indicated rs10499194, rs13207033 polymorphisms decreased the risk of RA among Caucasian populations, but not among Asian populations. In conclusion, this meta-analysis indicates that TNFAIP3 gene rs10499194, rs13207033 polymorphisms decrease the risk of RA, especially among Caucasian populations.
26957528 Smoking and Air Pollution as Pro-Inflammatory Triggers for the Development of Rheumatoid A 2016 Jul INTRODUCTION: Smoking is now well recognized not only as a risk factor for rheumatoid arthritis (RA), but also as a determinant of disease activity, severity, response to therapy, and possibly mortality. METHODS: Studies, mostly recent, which have provided significant insights into the molecular and cellular mechanisms which underpin the pathogenesis of smoking-related RA, as well as the possible involvement of other types of outdoor and indoor pollution form the basis of this review. RESULTS: Smoking initiates chronic inflammatory events in the lungs. These, in turn, promote the release of the enzymes, peptidylarginine deiminases 2 and 4 from smoke-activated, resident and infiltrating pulmonary phagocytes. Peptidylarginine deiminases mediate conversion of various endogenous proteins to putative citrullinated autoantigens. In genetically susceptible individuals, these autoantigens trigger the production of anti-citrullinated peptide, pathogenic autoantibodies, an event which precedes the development of RA. CONCLUSIONS: An increasing body of evidence has linked chronic inflammatory events in the lungs of smokers, to the production of anti-citrullinated peptide autoantibodies and development of RA. Creation of awareness of the associated risks, assessment of smoking status and implementation of compelling antismoking strategies must be included in the routine clinical management of patients presenting with suspected RA. IMPLICATIONS: Chronic inflammatory mechanisms operative in the lungs of smokers lead to the production of anti-citrullinated protein antibodies which, in turn, drive the development of RA. These mechanistic insights not only reinforce the association between smoking and risk for RA, but also the necessity to increase the level of awareness in those at highest risk.
25774937 Non-canonical NF-κB signaling in rheumatoid arthritis: Dr Jekyll and Mr Hyde? 2015 Jan 28 The nuclear factor-κB (NF-κB) family of transcription factors is essential for the expression of pro-inflammatory cytokines, but can also induce regulatory pathways. NF-κB can be activated via two distinct pathways: the classical or canonical pathway, and the alternative or non-canonical pathway. It is well established that the canonical NF-κB pathway is essential both in acute inflammatory responses and in chronic inflammatory diseases, including rheumatoid arthritis (RA). Although less extensively studied, the non-canonical NF-κB pathway is not only central in lymphoid organ development and adaptive immune responses, but is also thought to play an important role in the pathogenesis of RA. Importantly, this pathway appears to have cell type-specific functions and, since many different cell types are involved in the pathogenesis of RA, it is difficult to predict the net overall contribution of the non-canonical NF-κB pathway to synovial inflammation. In this review, we describe the current understanding of non-canonical NF-κB signaling in various important cell types in the context of RA and consider the relevance to the pathogenesis of the disease. In addition, we discuss current drugs targeting this pathway, as well as future therapeutic prospects.
27581587 Probiotic bacteria: a viable adjuvant therapy for relieving symptoms of rheumatoid arthrit 2016 Oct The burgeoning use of probiotics has proliferated during the past two decades. However, the effect of probiotic administration for either the prevention or treatment of rheumatoid arthritis (RA) has been investigated in a limited number of studies. Randomized controlled clinical trials have provided evidences that specific probiotics supplementation exhibit anti-inflammatory effects, help to increase daily activities and alleviate symptoms in patients with RA. Therefore, using probiotic bacteria as an adjuvant therapy may be considered as a promising treatment option for RA. This review summarizes the available data about the therapeutic and preventive effect of probiotics in RA, together with probiotic supplement as a possible therapy in clinical treatment.
26385261 Does the buck stop with the bugs?: an overview of microbial dysbiosis in rheumatoid arthri 2016 Jan The human body is an environmental niche which is home to diverse co-habiting microbes collectively referred as the human microbiome. Recent years have seen the in-depth characterization of the human microbiome and associations with diseases. Linking of the composition or number of the human microbiota with diseases and traits date back to the original work of Elie Metchnikoff. Recent advances in genomic technologies have opened up finer details and dynamics of this new science with higher precision. Microbe-rheumatoid arthritis connection, largely related to the gut and oral microbiomes, has showed up as a result - apart from several other earlier, well-studied candidate autoimmune diseases. Although evidence favouring roles of specific microbial species, including Porphyromonas, Prevotella and Leptotricha, has become clearer, mechanistic insights still continue to be enigmatic. Manipulating the microbes by traditional dietary modifications, probiotics, and antibiotics and by currently employed disease-modifying agents seems to modulate the disease process and its progression. In the present review, we appraise the existing information as well as the gaps in knowledge in this challenging field. We also discuss the future directions for potential clinical applications, including prevention and management of rheumatoid arthritis using microbial modifications.
27117623 [Potential of bone regenerative therapy with mesenchymal stem cells in rheumatoid arthriti 2016 May Mesenchymal stem cell(MSC)exists throughout the body. The discovery of the immunosuppressive effect with low immunogenicity has led MSC as a new tool for cell therapy in various diseases. Within the arthritis animal model, periarticular implantation of bone marrow derived MSC with a scaffold has demonstrated treatment effect with low cell number whereas systemic administration had limited effect. Bone marrow derived MSC suppressed in vitro osteoclastogenesis and osteoblastogenesis of MSC was enhanced in the presence of IL-1β.On the other hand, experiments with adipose-derived MSC suggested the involvement in abnormal tissue calcification in the presence of IL-6. Therefore, MSC generated from the appropriate tissue and clarification of the major cytokines involved in pathogenesis is necessary when considering regenerative therapy for destructed joint in RA patients.
27142378 [Novel immunodiagnostics for inflammatory arthritis]. 2016 May Immunodiagnostics play an important role in the differential diagnostics of arthritis but the test results must be interpreted with respect to the clinical context. The detection of antibodies against citrullinated proteins has significantly improved the immunodiagnostics of arthritis, whereas the importance of testing for rheumatoid factor has decreased due to the low specificity. Antibodies against carbamylated or oxidized proteins will expand the immunodiagnostics of arthritis (especially rheumatoid arthritis) in the future. In contrast, the determination of cytokine concentrations in plasma or synovial fluid plays a subordinate role in the differential diagnostics of arthritis. Indirect immunofluorescence continues to be the gold standard in the detection of antinuclear antibodies (ANA) and in the case of positive results further testing for antigen specificity should be carried out. The presence of ANA is not necessarily associated with autoimmune diseases. An example of a non-pathogenic ANA is anti-DFS70 antibodies.
28132045 THE ROLE OF T REGULATORY AND TH17 CELLS IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS (REVIE 2016 Dec Chronic inflammation of joints of autoimmune origin - rheumatoid arthritis - develops due to deplorable coincidence of genetic, immune and environmental factors. Th17 cells are considered as the main effector cells in the pathogenesis of rheumatoid arthritis. Analysis of many reports clarify positive correlation between the frequencies of circulating Th17 cells, serum levels of IL-17A and IL-23, synovial IL-17 and disease activity. Autoreactive Th clone response is regulated by the certain population of suppressor cells - T regulatory cells (Tregs). Contradictory results have been reported concerning Treg cell proportion in RA peripheral blood, but there is a general agreement on Treg cell enrichment in RA synovial fluid, that somehow compensates inflammation, but cytokine environment in the inflamed joint reduces functional activity of Tregs. Imbalance between Th17 and Treg cells may play a initiative role in RA pathogenesis because predominant Th17 cells can provoke vigorous pro-inflammatory response by producing IL-17 and impaired Tregs, partly due to the cytokine microenvironment, cannot regulate autoreactive immune response. Currently, a major focus of study in RA is to control IL-17 and modulate Treg activity in order to design new and improved therapies to limit inflammation and re-establish self-tolerance.
27814748 Glucocorticoids and endothelial function in inflammatory diseases: focus on rheumatoid art 2016 Nov 5 Rheumatoid arthritis (RA) is the most common systemic autoimmune disease characterized by articular and extra-articular manifestations involving cardiovascular (CV) diseases. RA increases the CV mortality by up to 50 % compared with the global population and CV disease is the leading cause of death in patients with RA. There is growing evidence that RA favors accelerated atherogenesis secondary to endothelial dysfunction (ED) that occurs early in the course of the disease. ED is a functional and reversible alteration of endothelial cells, leading to a shift of the actions of the endothelium towards reduced vasodilation, proinflammatory state, proliferative and prothrombotic properties. The mechanistic links between RA and ED have not been fully explained, but growing evidence suggests a role for traditional CV factors, auto-antibodies, genetic factors, oxidative stress, inflammation and iatrogenic interventions such as glucocorticoids (GCs) use. GCs have been used in RA for several decades. Whilst their deleterious CV side effects were described in the 1950s, their effect on CV risk associated with inflammatory arthritis remains subject for debate. GC might induce negative effects on endothelial function, via a direct effect on endothelium or via increasing CV risk factors. Conversely, they might actually improve endothelial function by decreasing systemic and/or vascular inflammation. The present review summarizes the available data on the impact of GCs on endothelial function, both in normal and inflammatory conditions, with a special focus on RA patients.
26697771 Arthroplasty in patients with established rheumatoid arthritis (RA): Mitigating risks and 2015 Aug Patients with rheumatoid arthritis (RA) continue to undergo arthroplasty to relieve pain and restore lost function caused by joint damage, despite improvements in disease-modifying therapy. The widespread use of potent immunosuppressant medications by RA patients implies that they frequently receive these drugs at the time of surgery. In addition to the medical challenges of medication and disease management at the time of surgery, there are surgical complexities related to complex deformities, osteoporotic bone, and ligament laxity. This paper discusses the current state of the art regarding arthroplasty utilization, outcomes, and perioperative management from a medical and surgical perspective, and highlights the clinical challenges to achieve optimal outcomes.