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

ID PMID Title PublicationDate abstract
28102705 The acetyl code in rheumatoid arthritis and other rheumatic diseases. 2017 Apr Growing evidence supports the idea that aberrancies in epigenetic processes contribute to the onset and progression of human immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Epigenetic regulators of histone tail modifications play a role in chromatin accessibility and transcriptional responses to inflammatory stimuli. Among these, histone deacetylases (HDACs) regulate the acetylation status of histones and nonhistone proteins, essential for immune responses. Broad-spectrum HDAC inhibitors are well-known anti-inflammatory agents and reduce disease severity in animal models of arthritis; however, selective HDAC inhibitors remain poorly studied. In this review, we describe emerging findings regarding the aberrant acetyl code in RA and other rheumatic disorders which may help identify not only novel diagnostic and prognostic clinical biomarkers for RA, but also new targets for epigenetic pharmacological applications.
28455580 Cardiovascular risk in patients with rheumatoid arthritis. 2017 Jun Substantial epidemiologic data have shown an increased risk of cardiovascular (CV) disease in rheumatoid arthritis (RA) patients. Traditional CV risk factors may partly contribute to CV disease in RA; however, current evidence underlines the important role of inflammation in the pathogenesis of atherosclerosis and amplification of CV risk. Interplays between inflammation and lipid metabolism in the development of atherosclerosis have been established by recent scientific advances. Atherosclerosis is currently viewed as an inflammatory disease, and modifications of lipoproteins during inflammation accelerate atherogenesis. The role of inflammation in the increased CV risk in RA has been further demonstrated by the CV protective effect of methotrexate and TNF antagonists, particularly in patients responding to these treatments. The management of CV risk in RA should include the use of effective disease-modifying anti-rheumatic drugs to control disease activity and the treatment of traditional CV risk factors.
28516435 Management Considerations in Cancer Patients With Rheumatoid Arthritis. 2017 May 15 Rheumatoid arthritis is a common inflammatory disease that requires treatment with immunosuppressants to control symptoms and avoid joint destruction. Managing cancer in patients with concomitant rheumatoid arthritis poses special challenges that require close coordination of care between oncologists and rheumatologists. Potential clinical issues needing special consideration include: 1) perioperative management in patients undergoing cancer surgery, which often requires discontinuation of antirrheumatic therapy; 2) use of immunosuppressant therapies for rheumatoid arthritis, especially biologic agents that inhibit cytokine and immune pathways, which conceivably could affect immune-mediated antitumor responses (the issues are different in patients with active cancer vs those with a past history of cancer and no recurrences); 3) management in the palliative care setting; and 4) use of cancer immunotherapy, such as checkpoint inhibitor agents, in patients with pre-existing rheumatoid arthritis. We explore these clinical issues in case-based scenarios. In all cases, clinical decision making must include a careful weighing of risks and benefits of both cancer treatments and antirrheumatic therapies, with attention given to prognosis and life expectancy, quality of life, and patient preferences.
29124698 Role of Vitamin D in Rheumatoid Arthritis. 2017 Vitamin D is a fat soluble hormone, with a well described role in bone health and calcium/phosphate metabolism. Recent evidences have related vitamin D to other physiological functions and pathological conditions. Specifically, vitamin D has widely proven activities on immune system and evidences suggest that it may be implicated in the pathogenesis of rheumatoid arthritis (RA). The relationship between vitamin D and RA is complex, also because a deficitary vitamin D status, which is very common in RA patients, can contribute to the increased risk of osteoporosis typical of RA. In this chapter, will be described and discussed the main aspects of the relationship between RA and vitamin D.
28736274 Biomarkers as a treatment guide in rheumatoid arthritis. 2018 Jan It is anticipated that biomarkers support rheumatologists to judge a group of patients that can improve the diagnosis and prognosis, and further facilitate appropriate and precise treatment with targeted therapy. In particular, biomarkers for predicting and monitoring response to biological disease modifying anti-rheumatic drugs (DMARDs) are demanding. Given the mechanism action of biological DMARDs is much more simple than the conventional synthetic DMARDs, a variety of approaches to find such biomarkers has been taken recent years. In this article, I will summarize the background for biomarker research and introduce recent topics in the research and the possible clinical applications of biomarkers to guide treatment in rheumatoid arthritis (RA).
29108829 TNF inhibitors in rheumatoid arthritis and spondyloarthritis: Are they the same? 2018 Jan The advent of anti-tumour necrosis factor (TNF) drugs for rheumatoid arthritis (RA) or spondyloarthritis (SpA) has revolutionised the approach to patients with active disease who do not respond to conventional therapy. Although there are differences in their structure, morphology, pharmacokinetic properties and activity, all anti-TNF drugs ultimately neutralise the TNFα pathway of inflammation. However, despite their similar clinical efficacy, there are disagreements concerning drug survival and safety, with systematic reviews and meta-analyses confirming one result or the other. The fact that 20-30% of patients fail to respond to TNFα inhibitors indicates the possibility of primary resistance or the development of an immune response to the drugs themselves, which may act as antigens. The overall benefit of switching to another anti-TNF drug or a biological agent with a different mechanism of action, may be a valuable option in individual patients. There are few data concerning the use of anti-TNF drugs in patients with SpA but it seems that there are fewer adverse advents and higher drug survival in comparison with patients with RA.
27811914 Update on the genetic architecture of rheumatoid arthritis. 2017 Jan Human genetic studies into rheumatoid arthritis (RA) have uncovered more than 100 genetic loci associated with susceptibility to RA and have refined the RA-association model for HLA variants. The majority of RA-risk variants are highly shared across multiple ancestral populations and are located in noncoding elements that might have allele-specific regulatory effects in relevant tissues. Emerging multi-omics data, high-density genotype data and bioinformatic approaches are enabling researchers to use RA-risk variants to identify functionally relevant cell types and biological pathways that are involved in impaired immune processes and disease phenotypes. This Review summarizes reported RA-risk loci and the latest insights from human genetic studies into RA pathogenesis, including how genetic data has helped to identify currently available drugs that could be repurposed for patients with RA and the role of genetics in guiding the development of new drugs.
27903225 Weight Bearing Joints Destruction In Rheumatoid Arthritis. 2017 In many cases of rheumatoid arthritis (RA) joints of the upper extremities are affected. However, involvement of weight bearing joints of the lower extremities is strongly associated with a decreased activities of daily living ability such as gait disorder. Once the progression of weight bearing joint destruction occurs, lower extremity function will decrease even if RA disease activity is improved by pharmacotherapy. In this article, we investigated joint destruction suppressing effects of pharmacotherapy on the hip and knee joints, as well as risk factors for joint destruction. We also discuss surgical treatment strategies and clinical outcomes for progressive joint destruction.
28757342 Rheumatoid arthritis treated with tocilizumab in two patients with complicated chronic liv 2018 Jan Erosive, active rheumatoid arthritis inpatients with portal hypertension combining esophageal varices and ascites complicating chronic liver disease poses serious management problems. Current literature does not provide any valid therapeutic management. We report the case of a woman and a man aged 52 and 66 years respectively having this combination of pathologies. Infusions of 4mg/kg of tocilizumab as monotherapy have produced a weaning from corticosteroids, both clinical and structural remission, with particular liver safety satisfactory at 10 and 18 months.
28711139 Human Leukocyte Antigen-Disease Associations in Rheumatoid Arthritis. 2017 Aug The cause and pathogenesis of rheumatoid arthritis (RA) are influenced by environmental and genetic risk factors. Shared epitope-coding human leukocyte antigen (HLA)-DRB1 alleles increase RA risk and severity; however, the underlying mechanisms of action remain unclear. In contrast, several other DRB1 alleles protect against RA. Additionally, genome-wide association studies suggest that RA associates with other, HLA and non-HLA, genes; but the relative contributions of such risk loci to RA are incompletely understood. Future research challenges include integrating the epidemiologic and genomic data into validated arthritogenic pathways and determining the mechanisms of interaction between RA risk genes and environmental influences.
28337522 Pre-symptomatic autoimmunity in rheumatoid arthritis: when does the disease start? 2017 Jun It is well recognised that a state of autoimmunity, in which immunological tolerance is broken, precedes the development of symptoms in the majority of patients with rheumatoid arthritis (RA). For individuals who will later develop seropositive disease, this manifests as autoantibodies directed against proteins that have undergone specific post-translational modifications. There is evidence that the induction of this autoantibody response occurs at peripheral extra-articular mucosal sites, such as the periodontium and lung. In addition to their utility as diagnostic markers, these autoantibodies may have a pathogenic role that helps localise disease to the synovium. Alongside the development of autoantibodies, other factors contributing to pre-symptomatic autoimmunity may include dysbiosis of the gastrointestinal tract, abnormal development of lymphoid tissue, and dysregulated autonomic and lipid-mediated anti-inflammatory signalling. These factors combine to skew the balance between pro-inflammatory and anti-inflammatory signalling in a manner that is permissive for the development of clinical arthritis. We present data to support the concept that the transitions from at-risk states to systemic autoimmunity and then to classifiable RA depend on multiple "switches". However, further prospective studies are necessary to define the molecular basis of these switches and the specific features of pre-symptomatic autoimmunity, so that preventative treatments can be targeted to individuals at high risk for RA. In this review, we analyse mechanisms that may contribute to the development of autoimmunity in at-risk individuals and discuss the relationship between this pre-symptomatic state and subsequent development of RA.
29017507 Polyunsaturated fatty acids: any role in rheumatoid arthritis? 2017 Oct 10 BACKGROUND: Polyunsaturated fatty acids (PUFAs) are members of the family of fatty acids and are included in the diet. Particularly, western diet is usually low in n-3 PUFAs and high in n-6 PUFAs. PUFAs play a central role in the homeostasis of immune system: n-6 PUFAs have predominantly pro-inflammatory features, while n-3 PUFAs seem to exert anti-inflammatory and pro-resolving properties. Rheumatoid arthritis (RA) is a chronic inflammatory arthritis in which many inflammatory pathways contribute to joint and systemic inflammation, disease activity, and structural damage. Research on PUFAs could represent an important opportunity to better understand the pathogenesis and to improve the management of RA patients. METHODS: We searched PubMed, Embase, EBSCO-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI and Wanfang to identify primary research reporting the role of n-3 PUFAs in rheumatoid arthritis both in humans and in animal models up to the end of March 2017. RESULTS: Data from animal models allows to hypothesize that n-3 PUFAs supplementation may represent an interesting perspective in future research as much in prevention as in treating RA. In humans, several case-control and prospective cohort studies suggest that a high content of n-3 PUFAs in the diet could have a protective role for incident RA in subjects at risk. Moreover, n-3 PUFAs supplementation has been assessed as a valuable therapeutic option also for patients with RA, particularly in order to improve the pain symptoms, the tender joint count, the duration of morning stiffness and the frequency of NSAIDs assumption. CONCLUSIONS: n-3 PUFAs supplementation could represent a promising therapeutic option to better control many features of RA. The impact of n-3 PUFAs on radiographic progression and synovial histopathology has not been yet evaluated, as well as their role in early arthritis and the combination with biologics.
29204672 Bone Loss in Rheumatoid Arthritis: Basic Mechanisms and Clinical Implications. 2018 May Patients with rheumatoid arthritis (RA) have historically developed progressive damage of articular bone and cartilage, which correlates with disability over time. In addition, these patients are prone to periarticular and systemic bone loss, carrying additional morbidity. In contrast to what is seen in many other rheumatic diseases, the impact of inflammation on bone in RA is uniquely destructive. Loss of articular bone (erosions) and periarticular bone (demineralization) is a result of excessive bone resorption and markedly limited bone formation. There has been tremendous progress in preventing net bone loss in RA with the advent of disease-modifying agents, including biologic agents and small molecules, that both limit inflammation and may have a direct impact on the prevention of cytokine- and antibody-driven osteoclastogenesis. However, repair of existing bone erosions, although feasible, is observed infrequently. Lack of repair is a consequence of suppression of osteoblast function and bone formation by some of the same mechanisms that promote osteoclastogenesis and bone resorption. As new agents are introduced to control inflammation in RA, and novel mechanisms to target synovitis are identified, it may be possible in the future to fully repair damaged bone.
28463872 Vitamin D and rheumatoid arthritis: an ongoing mystery. 2017 Jul PURPOSE OF REVIEW: In recent years, there has been a growing interest in the value of vitamin D and its effects on autoimmunity. The aim of this review is to summarize the current knowledge on the association between vitamin D and rheumatoid arthritis (RA) in terms of prevalence, disease activity, clinical expression, serology and gene polymorphisms of vitamin D receptors. RECENT FINDINGS: Studies have shown contrasting findings concerning the association between vitamin D levels and RA. Vitamin D seems to have immunomodulatory properties. Therefore, low vitamin D levels could contribute to increased immune activation. However, the potential role of vitamin D supplementation in preventing RA manifestation and its beneficial role as a component of RA treatment remain controversial. The relationship between RA susceptibility and vitamin D polymorphisms is also unclear. SUMMARY: Despite advancements synthesized by some recent meta-analyses, the relationship between vitamin D and RA requires further evaluation. Further research is needed to confirm the relationship between RA susceptibility and vitamin D polymorphisms and to determine whether vitamin D plays a role in preventing the manifestation of RA. Finally, additional studies are required to determine the impact and optimal amount of vitamin D supplementation in the treatment of RA patients.
28599756 Tripterygium wilfordii Inhibiting Angiogenesis for Rheumatoid Arthritis Treatment. 2017 Summer Rheumatoid arthritis (RA) is a chronic inflammatory disease with a serious pre-vascular inflammatory phase, followed by significant increase in vessel growth. Inhibition of angiogenesis is a novel therapeutic strategy against RA. The Chinese herbal remedy Tripterygium wilfordii, Hook. f. (TwHf) has been reported to be therapeutically efficacious in the treatment of RA. Recent studies have revealed that treatment with TwHf extracts inhibit angiogenesis of RA, thereby elaborately attenuation RA symptom. This review mainly addresses the anti-angiogenesis effect of TwHf in treatment of RA.
28635309 Rheumatoid arthritis is associated with negatively variable impacts on domains of female s 2018 Jan To systematically review the literature to identify the impact of rheumatoid arthritis (RA) on specific female sexual function domains. A meta-analysis was performed and the related literature were searched in MEDLINE, EMBASE, Cochrane Library, CNKI, CBM and Web of Science databases, and in reference lists of articles and systematic reviews. Score of the Female Sexual Function Index (FSFI) was used as the outcome measurement, and mean differences (MD) with 95% confidence intervals (CI) were calculated. Five studies were included, including 346 women with RA and 237 healthy female controls. Each domain of the FSFI score: lubrication (MD, -2.48; 95% CI, -3.69, -1.28), orgasm-1.71 (-2.09, -1.33), sexual desire-1.27 (-1.59, -0.95), satisfaction-1.67 (-2.18, -1.16), arousal-1.83 (-2.85, -0.82), pain-1.57 (-2.43, -0.70) and the total score -8.84 (-11.88, -5.79) were lower in RA women than healthy controls. Furthermore, lubrication dimension was most severely affected especially. This meta-analysis showed that female RA patients scored lower in each dimension of FSFI, mostly in the lubrication domain. It demonstrated that targeted interventions should be done to improve their sexual function. Future well-designed researches with larger sample sizes are necessary to evaluate the potential risk factors which determine female sexual dysfunction.
28366478 Immune Mechanisms and Novel Targets in Rheumatoid Arthritis. 2017 May Significant progress has been made in understanding the pathophysiology of rheumatoid arthritis. It is widely recognized that early institution of treatment is one of the best predictive factors for response to therapy. Several novel approaches are currently being investigated and several novel biologics are in various stages of development. With advances in the fields of proteomics, genomics, and metabolomics, specific phenotypes of the disease can be better identified and specific therapies for particular phases of the disease and specific patients will allow for improved control of this condition.
28497350 Synovial cellular and molecular markers in rheumatoid arthritis. 2017 Jun The profound alterations in the structure, cellular composition, and function of synovial tissue in rheumatoid arthritis (RA) are the basis for the persistent inflammation and cumulative joint destruction that are hallmarks of this disease. In RA, the synovium develops characteristics of a tertiary lymphoid organ, with extensive infiltration of lymphocytes and myeloid cells. Concurrently, the fibroblast-like synoviocytes undergo massive hyperplasia and acquire a tissue-invasive phenotype. In this review, we summarize key components of these processes, focusing on recently-described roles of selected molecular markers of these cellular components of RA synovitis.
28324133 Foot health in patients with rheumatoid arthritis-a scoping review. 2017 Sep Rheumatoid arthritis affects joints and can cause significant impairments in daily life. The foot is often the first site of symptoms and foot problems are strongly related to RA. The aim of this review was, therefore, to describe foot health in patients with rheumatoid arthritis and to identify how patients perform foot self-care. With this knowledge interventions to support foot health and functional ability in RA patients can be developed. The design of the review was a scoping review. A systematic literature search of three electronic databases, MEDLINE, CINAHL and Embase, was conducted in June 2016. The search yielded 1205 studies, of which 32 were selected for the review. The data were analysed by means of content analysis. Foot problems in RA patients are prevalent and impair their daily activities. Foot pain and foot structural deformities were the most prevalent problems. RA patients have difficulties caring their own feet and in finding proper footwear. Many different instruments were used to measure different aspects of foot health. Patients with RA have a high prevalence of foot and ankle problems. These foot problems are a major burden to patients themselves. RA patients' ability to self-care ability can be diminished, since RA also affects joints in the hands. In future cross-cultural validation studies are needed to ensure psychometrically sound instrumentation. Methods to alleviate foot pain and to prevent foot problems in RA patients need to be developed and tested.
28177937 Massage Therapy for Pain and Function in Patients With Arthritis: A Systematic Review of R 2017 Sep BACKGROUND: Massage therapy is gaining interest as a therapeutic approach to managing osteoarthritis and rheumatoid arthritis symptoms. To date, there have been no systematic reviews investigating the effects of massage therapy on these conditions. DESIGN: Systematic review was used. OBJECTIVES: The primary aim of this review was to critically appraise and synthesize the current evidence regarding the effects of massage therapy as a stand-alone treatment on pain and functional outcomes among those with osteoarthritis or rheumatoid arthritis. METHODS: Relevant randomized controlled trials were searched using the electronic databases Google Scholar, MEDLINE, and PEDro. The PEDro scale was used to assess risk of bias, and the quality of evidence was assessed with the GRADE approach. RESULTS: This review found seven randomized controlled trials representing 352 participants who satisfied the inclusion criteria. Risk of bias ranged from four to seven. Our results found low- to moderate-quality evidence that massage therapy is superior to nonactive therapies in reducing pain and improving certain functional outcomes. It is unclear whether massage therapy is more effective than other forms of treatment. CONCLUSIONS: There is a need for large, methodologically rigorous randomized controlled trials investigating the effectiveness of massage therapy as an intervention for individuals with arthritis.