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ID PMID Title PublicationDate abstract
28425787 Defining the proteomic landscape of rheumatoid arthritis: progress and prospective clinica 2017 May The heterogeneity of Rheumatoid Arthritis (RA) and the absence of clinical tests accurate enough to identify the early stages of this disease have hampered its management. Therefore, proteomics research is increasingly focused on the discovery of novel biological markers, which would not only be able make an early diagnosis, but also to gain insight into the different pathological mechanisms underlying the heterogeneity of RA and also to stratify patients, which is critical to enabling effective treatments. Areas covered: The proteomic approaches that have been utilised to provide knowledge about RA pathogenesis, and to identify biomarkers for RA diagnosis, prognosis, disease monitoring and prediction of response to therapy, are summarized. Expert commentary: Although each proteomic study is unique in its design, all of them have contributed to the understanding of RA pathogenesis and the discovery of promising biomarkers for patient stratification, which would improve clinical care of RA patients. Still, efforts need to be made to validate these findings and translate them into clinical practice.
28833093 Multifaceted role of IL-21 in rheumatoid arthritis: Current understanding and future persp 2018 May Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder designated with hyperplastic synovium, bone destruction and cartilage degradation. Current therapies involve targeting major cytokines and inflammatory mediators involved in RA to alleviate the pain and provide a temporary relief. Interleukin 21 (IL-21), a recently identified cytokine is known to possess a versatile role in modulating the cells of the RA synovium. Over the past decade, the pleiotropic role of IL-21 in RA pathogenesis has been implicated in several aspects. T helper 17 (Th17) and follicular T helper cells (Tfh), being the key immunomodulators of the RA synovium secrete high amounts of IL-21 during disease progression. Several studies have provided experimental evidences elucidating the multifaceted role of IL-21 in RA disease progression. IL-21 has the potential to activate T cells, B cells, monocytes/macrophages and synovial fibroblasts in RA pathogenesis through activation of JAK-STAT, MAPK and PI3K/Akt signaling pathways. Till date, therapies targeting Th17 cells and its inflammatory cytokines have been under investigation and are subjected to various clinical trials. This review showcases the role of IL-21 in RA pathogenesis and recent reports implicating its function in various immune cells, major signaling pathways, and in promoting osteoclastogenesis.
29221594 Periodontal disease and periodontal bacteria as triggers for rheumatoid arthritis. 2017 Feb There is an epidemiological association between periodontitis and rheumatoid arthritis (RA), which is hypothesised to lead to enhanced generation of RA-related autoantibodies that can be detected years before the onset of RA symptoms. Periodontitis is a common dysbiotic disease; tissue damage occurs because the immune system fails to limit both the resident microbial community and the associated local immune response. Certain periodontal bacteria, including Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, may contribute to RA autoantibody production through direct post-translational modification of proteins or, indirectly, by influencing neutrophil-mediated neo-epitope generation. Oral bacteria that invade the blood may also contribute to chronic inflammatory responses and generation of autoantibodies. The putative association between periodontitis and the development of RA raises the potential of finding novel predictive markers of disease and disease progression and for periodontitis treatment to be included in the future as an adjunct to conventional RA immunotherapy or as part of a preventive strategy.
28205331 New insights to the mechanisms underlying atherosclerosis in rheumatoid arthritis. 2017 Mar Rheumatoid arthritis (RA) is an inflammatory circumstance, which has been associated with increased risk of cardiovascular disease (CVD). Although RA management has been promoted, mortality rate due to CVD remains remarkable. Approximately, 50% of premature death cases in RA are attributable to CVD. RA patients develop atherosclerosis in a greater amount than the general population. Moreover, atherosclerotic lesions develop rapidly in RA patients and might be more susceptible to rupture. The inflammatory condition of RA, such as cytokines, abnormally activated immune cells, play a role in the initiation, perpetuation and exacerbation of atherosclerosis. RA and CVD have genetic and environmental contributing risk factors in common, implying to potential coincidence of both disorders. Accelerated atherosclerosis in RA is attributed to inflammation, which carries its role out both through modulation of traditional risk factors and direct effect on the vessel wall. Hence, anti-inflammatory medications in RA like tumor necrosis factor blockers might have a beneficial effect on preventing cardiovascular development. Increasing age, smoking, hypertension, male gender, hypercholesterolemia and diabetes are enumerated as traditional CVD risk factors. Hopefully, further understanding of the cardiovascular risk factors by perceiving the disease conditions behind CVD, will improve management of cardiovascular risks in patients with RA.
28707487 The role of genetic analysis for predicting outcome of rheumatoid arthritis. 2017 Sep Rheumatoid Arthritis (RA) varies from a mild to a severe, unremitting illness characterized by uncontrolled inflammation with consequent damage to cartilage and bone of joints. Individualized therapeutic approaches based on likely outcome would facilitate a personalized therapeutic approach. Areas covered: Genetics is known to contribute a significant component of the variability in RA outcome, estimated at 45-60%. A number of candidate gene studies have been associated with variability in radiologically assessed joint damage; however a more comprehensive genome wide analysis is required to more fully characterize the genetic basis of RA severity. Expert commentary: Genetic profiling of patient presenting with RA has the potential to aid stratification based on predicted prognosis, this would inform the clinical development of a personalized therapeutic approach. It will also result in the identification of novel mediators of tissue damage in RA.
28872725 Dorsal Root Ganglion Field Stimulation Prevents Inflammation and Joint Damage in a Rat Mod 2018 Apr OBJECTIVES: Electrical stimulation of the dorsal root ganglion (DRG), referred to here as ganglionic field stimulation (GFS), is effective in reducing clinical pain, probably by interrupting transmission of afferent impulse trains on sensory neurons as they pass through the DRG. We therefore tested whether efferent impulse trains conveyed by sensory neurons, which contribute to neurogenic inflammation, may also be interrupted by GFS. MATERIALS AND METHODS: Collagen-induced arthritis, a model of clinical rheumatoid arthritis, was initiated in rats concurrently with the insertion of an electrode for GFS at the fourth lumbar DRG. Continuous GFS (20 Hz pulse rate, current at 80% of the motor threshold) was initiated 6 days later and continued for 14 days. Plantar pain sensitivity, ankle arthritis score, and dimensions of the foot and ankle were determined one hour after termination of GFS. RESULTS: The foot/ankle contralateral to GFS developed hypersensitivity to threshold and noxious mechanical stimulation, swelling, and high arthritis score, all of which were normalized in the foot/ankle ipsilateral with GFS. Histology showed GFS limited joint destruction. Electrophysiological recording showed GFS can block efferent impulse trains. CONCLUSIONS: Our findings show that GFS can reduce neurogenic inflammation and the resulting joint damage in a model of rheumatoid arthritis, probably by blocking the transit of impulse trains through the DRG. GFS may have clinical utility in limiting joint destruction in inflammatory arthritis such as rheumatoid arthritis.
28861200 Reverse Shoulder Arthroplasty in Patients with Rheumatoid Arthritis: A Systematic Review. 2017 Sep BACKGROUND: There are limited data available regarding the results of reverse shoulder arthroplasty (RSA) in patients with rheumatoid arthritis (RA). We performed a systematic review of the literature to investigate the radiological and clinical outcomes after RSA in patients with RA. METHODS: A literature search for publications between 1987 and 2014 was conducted by 2 independent reviewers using PubMed, Scopus, Embase, and Cochrane Central Register of Controlled Trials. Articles were retrieved by an electronic search using keywords and their combinations. Studies that met inclusion criteria were assessed for pertinent data. RESULTS: Seven studies including 123 shoulders met the inclusion criteria. The mean age of the patients was 67.9 years and the mean follow-up period was 46.6 months. The mean Constant score and American Shoulder and Elbow Surgeons (ASES) score increased from 18.6 and 27.5 preoperatively to 58.6 and 73.7, respectively, at the final follow-up evaluation. The mean active forward flexion, abduction, and external rotation increased from 57.2°, 50.4°, and 11.4° to 127.1°, 116.7°, and 26.4°, respectively. The incidence of scapular notching was 33.7%. Twenty-seven (22.0%) of 123 shoulders had one or more complications, 12 of which (44.4%) had intraoperative or postoperative fractures. Nine shoulders (7.3%) had one or more revision surgeries. CONCLUSIONS: RSA in RA showed similar short- to mid-term results without higher complication rates as compared to RSA in cuff tear arthropathy. Although RSA can be considered a reliable treatment option in patients with RA, further large-scale studies are required to determine the long-term survival of the implant.
28805201 [Osteoporosis and vascular calcification in rheumatoid arthritis - the role of osteoproteg 2017 Jul 21 Disorders of bone tissue metabolism and increased frequency of cardiovascular diseases are among the well-known, extra-articular complications of rheumatoid arthritis (ra). The mechanisms leading to local and generalized loss of bone tissue as well as those promoting calcification of vessels are similar. Recently, a great interest has aroused among the studies related to the meaning of the RANKL/RANK/OPG system and the Wnt/β-catenin signaling pathway, as biological links between the bone and vascular systems. In the course of ra, lowering of the mineral density of bones and intensification of vascular calcification seem to be associated with the increase of plasma concentration of osteoprotegerin (OPG) and sclerostin - the regulatory proteins of the RANKL/RANK/OPG system and the Wnt/β-catenin pathway. Molecular mechanisms associated with the osteoblasts' activation and repression of bone resorption in the future can become the target of a precise, combination therapy in osteoporosis and calcification changes. The article presents the role of the RANKL/RANK/ OPG system and the Wnt/β-catenin pathway in the pathogenesis of disorders of bone tissue metabolism and calcification of vessels in ra, with particular emphasis on the role of OPG and sclerostin.
28547815 Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis. 2017 Jul Imbalance in the autonomic nervous system (ANS) has been observed in many established chronic autoimmune diseases, including rheumatoid arthritis (RA), which is a prototypic immune-mediated inflammatory disease (IMID). We recently discovered that autonomic dysfunction precedes and predicts arthritis development in subjects at risk of developing seropositive RA. In addition, RA patients with relatively high vagus nerve tone (higher parasympathetic parameters, measured by heart rate variability) respond better to antirheumatic therapies. Together, these data suggest that the ANS may control inflammation in humans. This notion is supported by experimental studies in animal models of RA. We have found that stimulation of the so-called cholinergic anti-inflammatory pathway by efferent electrical vagus nerve stimulation (VNS) or pharmacological activation of the alpha7 subunit of nicotinic acetylcholine receptors (α7nAChR) improves clinical signs and symptoms of arthritis, reduces cytokine production and protects against progressive joint destruction. Conversely, increased arthritis activity was observed in alpha7nAChR knockout mice. These studies together with previous work in animal models of sepsis and other forms of inflammation provided the rationale for an experimental clinical trial in patients with RA. We could for the first time show that an implantable vagus nerve stimulator inhibits peripheral blood cytokine production in humans. VNS significantly inhibited TNF and IL-6 production and improved RA disease severity, even in some patients with therapy-resistant disease. This work strongly supports further studies using a bioelectronic approach to treat RA and other IMIDs.
27412376 Meta-analyses of the association of HLA-DRB1 alleles with rheumatoid arthritis among Arabs 2017 Jul AIM: Various studies incorporating Arab populations have reported on specific associations between HLA-DRB1 variants and rheumatoid arthritis (RA). We sought to provide an overview on the association of HLA-DRB1 with RA in Arabs using meta-analysis tools. METHODS: Data on allele counts and frequencies were compiled from the relevant literature (published before 16 February 2016) and the associations of 13 -DRB1 variants with RA were assessed; relationships were defined in terms of odds ratios (ORs) with a 95% confidence interval. RESULTS: Based on a collection of six studies, risk conferring or protective allele associations were derived from allele counts in 475 RA patients and 1213 controls. Two HLA-DRB1 alleles (-DRB1*04, *10) significantly conferred an increased risk for RA (OR > 2; P < 0.0001). Conversely, four alleles (-DRB1*03, *07, *11 and *13) significantly conferred a protective effect against RA (OR < 1; P < 0.05). No significant associations with RA were found for seven -DRB1 variants (-DRB1*01, *08, *09, *12, *14, *15 and *16). CONCLUSION: With increased statistical power and effect size over individual studies, we present a more robust profile on the association of HLA-DRB1 variants with RA in the Arab ethnicity, and contribute to the global geo-ethnic picture in this context.
28842173 MicroRNAs and bioactive compounds on TLR/MAPK signaling in rheumatoid arthritis. 2017 Oct Rheumatoid arthritis (RA) is a chronic autoimmune mediated joint disease with severe complications affecting 1% of the population worldwide. Although the exact mechanism underlying the aggravation of RA remains unknown, its occurrence can lead to joint degradation and functional disability. Recent evidences have shown that the aberrant expression of microRNAs (miRNAs) play a prominent role in the furtherance of RA. Over the last decade, various intensive studies have validated different microRNAs to be good candidates for diagnostic purposes and for monitoring the disease progression in various inflammatory diseases. A deeper understanding of the molecular mechanism through which miRNAs amplify the production of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17), pro-inflammatory mediators, growth factors and MMPs will act as potential therapeutic targets. More importantly, several studies have briefly reported the crucial role of TLR dependent MAPK signaling pathway, which mediates the pathological features of RA. In this review, we summarize the recent findings and provide a detailed report of the molecular mechanism of microRNA along with the role of TLR/MAPK signaling pathway in RA. However, the major aim of this review is to correlate the aberrantly expressed microRNAs in TLR/MAPK pathway with various well reported bioactive compounds that can modulate these signaling pathways in rheumatoid arthritis. Targeting miRNA expression using specific bioactive compounds might be a potent and an effective target in RA treatment by suppressing the TLR/MAPK pathway.
28251248 Does exercise impact on sleep for people who have rheumatoid arthritis? A systematic revie 2017 Jun To systematically search for the availability of evidence for exercise impacting on sleep for people who have rheumatoid arthritis. Two reviewers independently searched seven electronic databases, identified and extracted relevant studies by applying eligibility criteria. Sources of bias were assessed independently by two reviewers using the Cochrane bias assessment tool for randomized controlled trials (RCTs) and Newcastle-Ottawa Quality Assessment Scale for non-RCTs. Data were synthesized using a level of evidence approach. Meta-analyses were deemed to be inappropriate due to the heterogeneity of study designs, measurement tools and interventions. Five studies were included: one RCT; two pilot RCTs and two samples of convenience. A total of 262 people with RA were included. Interventions used were difficult to assess due to the heterogeneity of study designs and the inclusion of two using different types of yoga as an intervention. Different sleep outcome measures were used thus, it was not feasible to pool results. Studies had a high risk of bias. This review could find no consistent or conclusive evidence on whether exercise impacts on sleep in people who have rheumatoid arthritis, therefore no firm conclusions can be made. However, there is some indication that exercise may have positive benefits on sleep in people who have rheumatoid arthritis. Further studies with improved study designs, using subjective and objective measures, are needed.
28205390 Circulating adiponectin and visfatin levels in rheumatoid arthritis and their correlation 2018 Mar AIM: This study aimed to evaluate the relationship between circulating adiponectin and visfatin levels and rheumatoid arthritis (RA) and to establish a correlation between serum adipokine levels and RA activity. METHODS: We conducted meta-analyses on serum/plasma adiponectin or visfatin levels in patients with RA and controls and correlation coefficients between circulating adiponectin and visfatin levels and Disease Activity Score of 28 joints (DAS28) in RA patients. RESULTS: Eleven studies comprising 813 RA patients and 684 controls were included in this meta-analysis. The meta-analysis revealed that adiponectin levels were significantly higher in the RA group than in the control group (standardized mean difference [SMD] = 1.529, 95% confidence interval [CI] = 0.354-2.704, P = 0.011). Circulating adiponectin level was not associated with RA activity based on DAS28 and C-reactive protein (CRP) levels. Visfatin levels were significantly higher in the RA group than in the control group (SMD = 2.575, 95% CI: = 0.963-4.189, P = 0.002). A trend of positive correlation among circulating visfatin levels and DAS28 and CRP levels was found (correlation coefficient = 0.416, 95% CI: = -0.917 to 0.795, P = 0.177; correlation coefficient = 0.366, 95% CI: = -0.074 to 0.687, P = 0.101, respectively). CONCLUSIONS: Our meta-analysis demonstrated that circulating adiponectin levels were significantly higher in patients with RA than in controls. Circulating visfatin levels were significantly higher in patients with RA than in controls and a positive correlation between circulating visfatin level and RA activity is suggested.
27739363 The Effect of Treatments for Rheumatoid Arthritis on Endothelial Dysfunction Evaluated by 2017 Rheumatoid Arthritis (RA) is a chronic inflammatory disease with a potential cardiovascular (CV) risk. Flow-Mediated Vasodilation (FMD) is an ultrasonic method to evaluate endothelial function. RA is a contributor to endothelial dysfunction, a CV risk. Relevant insights on the improvement of the CV outcomes in RA patients may be obtained by a systematic review of trials that investigated the effects of RA treatment on FMD in RA patients. This review found that treatments with antirheumatic drugs and some non-antirheumatic drugs could improve the FMD in RA patients. Treatment with anti-tumour necrosis factor (TNF)-α drugs, including infliximab, etanercept and adalimumab, improved the FMD in RA patients. Treatment with non-anti-TNF-α drugs, including rituximab, anakinra and tocilizumab, also improved the FMD. One trial showed that conventional synthetic Disease-Modifying Antirheumatic Drugs (DMARDs) improved the FMD. Regarding non-antirheumatic drugs, treatment with ramipril, spironolactone and statins/ezetimibe improved the FMD in RA patients. Treatment of advanced glycation endproducts inhibitors improved the FMD in RA patients, while treatment of pioglitazone did not. Overall, treatments for RA improved endothelial dysfunction, as evaluated by FMD, in RA patients. This information may be useful in patient management, although further studies are necessary to establish strategies in relation to endothelial dysfunction among these patients.
28516867 The link between Proteus mirabilis, environmental factors and autoantibodies in rheumatoid 2017 Sep Rheumatoid arthritis (RA) is a relatively common and potentially disabling immune-mediated inflammatory systemic disease, predominantly affecting women and characterised by multiple small joint arthritis. Extensive data supports the roles of genetic, environmental and microbial factors in the triggering and development of this disease. Proteus mirabilis is considered as the main microbial culprit in the causation of RA. The evidence for the role of these microbes in RA and their links with commonly associated autoantibodies such as rheumatoid factors and anti-citrullinated peptide antibodies have been elucidated together with their relations with some of the non-microbial environmental factors which have been implicated in the aetiopathogenesis of RA. The most likely mechanism in the development of RA is "molecular mimicry" where Proteus antigens were found to share homologous sequences, which cross-react with certain self-antigens present in synovial tissues. This could raise possibilities for implementing a new therapeutic strategy in the treatment of RA.
28361332 Managing Cardiovascular Disease Risk in Rheumatoid Arthritis: Clinical Updates and Three S 2017 Apr ᅟ: The increase in cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) is well known; however, appropriate management of this elevated risk in rheumatology clinics is less clear. PURPOSE OF REVIEW: By critically reviewing literature published within the past 5 years, we aim to clarify current knowledge and gaps regarding CVD risk management in RA. RECENT FINDINGS: We examine recent guidelines, recommendations, and evidence and discuss three approaches: (1) RA-specific management including treat-to-target and medication management, (2) assessment of comprehensive individual risk, and (3) targeting traditional CVD risk factors (hypertension, smoking, hyperlipidemia, diabetes, obesity, and physical inactivity) at a population level. Considering that 75% of US RA visits occur in specialty clinics, further research is needed regarding evidence-based strategies to manage and reduce CVD risk in RA. This review highlights clinical updates including US cardiology and international professional society guidelines, successful evidence-based population approaches from primary care, and novel opportunities in rheumatology care to reduce CVD risk in RA.
29200665 The Role of High-Mobility Group Box-1 and Its Crosstalk with Microbiome in Rheumatoid Arth 2017 Rheumatoid arthritis (RA) is a chronic, definitely disabling, and potentially severe autoimmune disease. Although an increasing number of patients are affected, a key treatment for all patients has not been discovered. High-mobility group box-1 (HMGB1) is a nuclear protein passively and actively released by almost all cell types after several stimuli. HMGB1 is involved in RA pathogenesis, but a convincing explanation about its role and possible modulation in RA is still lacking. Microbiome and its homeostasis are altered in patients with RA, and the microbiota restoration has been proposed to patients with RA. The purpose of the present review is to analyze the available evidences regarding HMGB1 and microbiome roles in RA and the possible implications of the crosstalk between the nuclear protein and microbiome in understanding and possibly treating patients affected by this harmful condition.
29238722 Clinical, Epidemiological, and Histopathological Features of Respiratory Involvement in Rh 2017 Although by definition rheumatoid arthritis (RA) is an articular disorder, it is a systemic disease, and 18-40% of patients experience extra-articular manifestations (EAMs). The involvement of the respiratory system occurs in about 30-40% of RA patients, and in about 10-20% of them it represents the first manifestation of RA. A wide range of pulmonary manifestations are detectable in RA patients, including pulmonary parenchymal disease, pleural involvement, and airway and pulmonary inflammation. The clinical, radiological, and histological spectra of respiratory manifestations in RA reflect chronic immune activation, increased susceptibility to infection (often related to immunosuppressive medications), or direct drug. The type and severity of pulmonary involvement influence the prognosis, ranging from mild self-limiting conditions to severe life-threatening complications. Herein, we reviewed the various manifestations of respiratory involvement in RA, providing an overview on epidemiological, histological, clinical, and radiological data.
28899798 Is ACPA positivity the main driver for rheumatoid arthritis treatment? Pros and cons. 2017 Nov Rheumatoid Arthritis (RA) is an autoimmune chronic disease that is characterized by the positivity of various antibodies, the most specific being autoantibodies against citrullinated antigens (ACPA). Despite ACPA are not arthritogenic by themselves, ACPA positive individuals have high risk of RA development and ACPA positivity is associated with severe erosive phenotype and higher mortality rate compared to seronegative RA. Moreover, ACPA status is associated with favorable response to biologics targeting pathways involving autoantibody producing cells as B lymphocytes. In the current review we have discussed the pros and cons on the available scientific evidences, regarding the diagnostic, prognostic and management implications of ACPAs in RA.
27503624 cDNA phage display for the discovery of theranostic autoantibodies in rheumatoid arthritis 2017 Feb Rheumatoid arthritis (RA) is the world's most common autoimmune disease mainly characterized by a chronic inflammation of multiple synovial joints. Rheumatologists now have a whole range of treatment options including glucocorticoids (GCs), classical synthetic and biological disease-modifying antirheumatic drugs (cs- and bDMARDS), resulting in a tremendous improvement in treatment outcomes for RA patients over the last two decades. Despite this progress, the choice of treatment regimen to achieve stable remission at the individual patient level still largely depends on trial and error. In this review, the need for novel theranostic markers that can predict a patient's response to methotrexate, the standard first-line csDMARD treatment, is discussed. Like in many autoimmune diseases, the majority of RA patients form a whole range of autoantibodies. We aim to find novel theranostic autoantibody markers using serological antigen selection, a high-throughput technique that uses cDNA phage display to identify novel antigen targets. We have constructed a barcoded cDNA phage display library from the synovial tissue of three RA patients by fusing cDNA products to the filamentous phage minor coat protein VI. This library contains a large proportion of full-length genes and gene fragments that are cloned in frame with the phage gene VI. By screening this library for antibody reactivity in serum samples of patients from the CareRA trial, which compared different intensive treatment strategies based on csDMARDs and a step-down GC schedule, our cDNA phage display library has great potential for the discovery of novel theranostic autoantibody biomarkers.