Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 21339228 | microRNAs in rheumatoid arthritis: midget RNAs with a giant impact. | 2011 Mar | MicroRNAs (miRNAs) are tiny, non-coding molecules that primarily modulate gene expression at the post-transcriptional level by predominantly hybridising to complementary sequences in the 3'-untranslated region of their corresponding mRNAs. Depending on the degree of Watson-Crick base pairing, a miRNA either accelerates the degradation of the corresponding transcript or restricts its translation. There is compelling evidence that miRNAs have crucial roles in controlling and modulating immunity, while dysregulation of miRNAs can lead to autoimmunity and promote tumourigenesis, making miRNA regulation a balancing act between immunity and tumourigenesis. Here, the focus is on the role of miRNAs during the establishment and sustainment of rheumatoid arthritis (RA), a systemic, inflammatory autoimmune disease with irreversible joint destruction. An overview of the known function of miRNAs in RA and what the future might hold for the use of these small RNA molecules in RA diagnosis and treatment is provided. | |
| 22265259 | The synovium as a privileged site in rheumatoid arthritis: cadherin-11 as a dominant playe | 2011 Dec | Rheumatoid arthritis is a systemic disease in which an autoimmune response translates primarily into joint inflammation with attendant joint destruction. While evidence implicates both the adaptive and innate immune system in rheumatoid synovitis, several lines of evidence now support the concept that the synovial tissue itself actively participates in the destructive inflammatory processes of arthritis. Specifically, the resident mesenchymal cells, the fibroblast-like synoviocytes (FLSs), frame a synovial microenvironment that responds to, augments and perpetuates the inflammatory process. Moreover, the FLSs have been recognised as the dominant cells mediating joint destruction. The identification of cadherin-11 expression on FLS provided an opportunity to unravel molecular mechanisms by which these resident mesenchymal cells govern processes that result in destructive synovitis in the context of systemic autoimmune disease. Herein, we discuss the unfolding biology of the synovial cadherin with its implications for the synovial pathology in arthritis, especially rheumatoid arthritis. | |
| 22819092 | Environmental and gene-environment interactions and risk of rheumatoid arthritis. | 2012 May | Multiple environmental factors including hormones, dietary factors, infections, and exposure to tobacco smoke, as well as gene-environment interactions, have been associated with increased risk for rheumatoid arthritis (RA). The growing understanding of the prolonged period before the first onset of symptoms of RA suggests that these environmental and genetic factors are likely acting to drive the development of RA-related autoimmunity long before the appearance of the first joint symptoms and clinical findings that are characteristic of RA. This article reviews these factors and interactions, especially those that have been investigated in a prospective fashion before the symptomatic onset of RA. | |
| 22685274 | Disease control with glucocorticoid therapy in rheumatoid arthritis. | 2012 Jun | DMARDs aim to improve long-term prognosis of RA, as indicated by reduced progression of radiographic damage and maintenance of function. However, it may be more appropriate to consider disease-modifying strategies rather than drugs alone. Despite the challenges (e.g. lack of standard outcome measures, poor reporting of dose levels), a systematic review of 15 studies involving more than 1400 patients showed that glucocorticoid treatment for 1-2 years slowed radiographic progression compared with control treatment. Evidence for longer term disease-modifying benefits of glucocorticoids comes from individual studies with extended follow-up. In the Utrecht study, patients with early RA originally assigned to prednisone 10 mg/day for 2 years and then tapered off the therapy showed significantly less radiographic progression at follow-up after a further 3 years than patients originally assigned placebo, with no significant difference in the use of synthetic DMARD therapy. In the combination therapy in early RA (COBRA) study, patients with newly diagnosed RA treated with glucocorticoid (starting with 60 mg/day, quickly reduced to 7.5 mg/day for weeks 7-28 and subsequently stopped), MTX up to week 40 and SSZ showed significantly decreased radiographic progression compared with those treated with SSZ alone. The benefits of short-term combination therapy on disease progression were still apparent at 5-year and 11-year follow-up. In conclusion, there is clear evidence that treatment regimens including low-dose glucocorticoids given early in RA slow radiographic progression, meeting the definition of a DMARD. Furthermore, the evidence suggests that such treatment strategies favourably alter the disease course even after glucocorticoid discontinuation. | |
| 22137926 | Quality of life and the outcome of established rheumatoid arthritis. | 2011 Aug | Rheumatoid arthritis (RA) is a long-term condition causing joint pain and swelling and sometimes systemic involvement. The aims of treatment are, first, to reduce the impact the disease has on a patient and, second, to halt progression of disease. The advent of intensive therapy, including biologics, has led to a major improvement in outcome. To assess treatment impact, formal outcome measures have been developed. Traditionally, these focussed on the clinical aspects such as disease activity and joint damage. More recently, there has been an increased focus on patient-related outcome measures including quality-of-life measures. These enable illness evaluation from patients' perspectives, examination of care quality and comparison of the effectiveness and cost-effectiveness of treatment. This article examines advantages and disadvantages of the various outcome measures which are generally used in RA, with a focus on quality of life and patient-related measures. | |
| 22608957 | Management of rheumatoid arthritis in Spain (emAR II). Clinical characteristics of the pat | 2012 Sep | BACKGROUND: There is a wide variability in the diagnostic and therapeutic methods in rheumatoid arthritis (AR) in Spain, according to prior studies. The quality of care could benefit from the application of appropriate clinical practice standards; we present a study on the variability of clinical practice. METHODS: Descriptive review of clinical records (CR) of patients aged 16 or older diagnosed with RA, selected by stratified sampling of the Autonomous Communities in two stages per Hospital Center and patient. Collected analysis of sociodemographic data, evolution, follow-up, joint count, reactants, function, job history, Visual Analogue Scales (VAS) and other. RESULTS: We obtained valid information of 1,272 RA patients. The ESR, CRP and rheumatoid factor (RF) were regularly used parameters. The percentages of missing data in tender (TJN) and swollen (SJN) joint counts were 8.2% and 9.6% respectively; regarding the VAS we found 53.6% (patient), 59.1% (pain), and 72% in the physician VAS. CONCLUSIONS: Despite having clinical practice guidelines on RA, there still exists a significant variability in RA management in our country. | |
| 21732051 | Anti-citrullinated protein antibodies (ACPA) in early rheumatoid arthritis. | 2012 Feb | Autoantibodies with the highest specificity for rheumatoid arthritis (RA) are the antibodies directed to citrulline-containing epitopes, so-called anti-citrullinated peptide/protein antibodies (ACPA). During the past decade it became clear that the presence of these antibodies was highly predictive of and specific for RA, and illustrating the importance of ACPA. Therefore, the presence of these antibodies is one of the new American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria for RA. Apart from the presence of these antibodies, the composition of this antibody response matures during RA development. This review summarizes the current knowledge of the characteristics of ACPA in RA development. | |
| 21515267 | Effector T cells in rheumatoid arthritis: lessons from animal models. | 2011 Dec 1 | The development of an immune response to self antigens drives naive T cells to differentiate into subsets of CD8(+) and CD4(+) effector cells including T(H)1, T(H)2, cells and the more recently described T(H)17, and regulatory T cells (T(reg)). Rheumatoid arthritis is an autoimmune disease that engages an uncontrolled influx of inflammatory cells to the joints, eventually leading to joint damage. The role that effector T cells play in the local or systemic maintenance of, or protection against, inflammation and subsequent joint damage is now becoming better understoodthrough the use of animal models. In this review, we will explore the different animal models of RA, and their contribution to elucidating the role that effector T cells play in the regulation, induction, and maintenance of inflammatory joint disease. This understanding will aid in the design of more effective therapeutic strategies for rheumatoid arthritis and other autoimmune disorders. | |
| 22011672 | Amyloid A amyloidosis secondary to rheumatoid arthritis: pathophysiology and treatments. | 2011 Sep | The introduction of biological therapies targeting specific inflammatory mediators revolutionised the treatment of rheumatoid arthritis (RA). Targeting key components of the immune system allows efficient suppression of the pathological inflammatory cascade that leads to RA symptoms and subsequent joint destruction. Reactive amyloid A (AA) amyloidosis, one of the most severe complications of RA, is a serious, potentially life-threatening disorder caused by deposition of AA amyloid fibrils in multiple organs. These AA amyloid fibrils derive from the circulatory acute-phase reactant serum amyloid A protein (SAA), and may be controlled by treatment. New biologics may permit AA amyloidosis secondary to RA to become a treatable, manageable disease. Rheumatologists, when diagnosing and treating patients with AA amyloidosis secondary to RA, must understand the pathophysiology and clinical factors related to development and progression of the disease, including genetic predisposition and biological versatility of SAA. | |
| 21386796 | Unresolved issues in biologic therapy for rheumatoid arthritis. | 2011 Apr | The advent of biologic therapies for the treatment of rheumatoid arthritis (RA) has radically changed this therapeutic area. The currently available biologic agents have been studied extensively as part of their development and also during their subsequent years of use in clinical practice; as a result, the knowledge base regarding these therapeutics is very large. Nonetheless, a number of important questions remain and some key issues are still incompletely understood. In this Review, I discuss a number of these unresolved issues, including: the correct placement of biologic therapies in the long-term evolution of the RA disease process, and the expectations associated with such use; comparisons of therapeutic strategies that include conventional as well as biologic agents; optimal dosing of biologic agents; the elusive goal of personalized therapy; and an appraisal of the real impact of biologic therapy on patients' lives. It is concluded that, despite these unresolved issues, important progress has been made and many additional advances in our understanding can be expected during the coming years. | |
| 22703866 | Vascular calcification in rheumatoid arthritis: prevalence, pathophysiological aspects and | 2012 Oct | Individuals with rheumatoid arthritis (RA) are at increased risk for morbidity and mortality from cardiovascular disease. Excess cardiovascular mortality in RA patients cannot be fully explained by conventional cardiovascular risk factors. The purpose of this review is to discuss recent progress concerning the prevalence and pathophysiological aspects of vascular calcification in RA. RA patients have early-onset diffuse calcification involving multiple vascular beds compared to age and sex-matched controls. Pathogenesis of vascular calcification in RA patients is not fully understood, but specific mediators such as proinflammatory cytokines and not global inflammation could be involved. The possible link between osteoporosis and vascular calcification in RA will not be discussed. Finally, potential targets to reduce vascular calcification in RA will be discussed. | |
| 23230093 | Imaging tools in rheumatoid arthritis: ultrasound vs magnetic resonance imaging. | 2012 Dec | As modern imaging tools such as US and MRI become increasingly available, rheumatologists now have access to highly sensitive measures to assist in the evaluation of both the inflammatory and structural damage components underlying various arthritides over the disease duration. Both US and MRI have associated strengths and weaknesses, and at times they can provide complementary information. This review compares the performance of US vs MRI as diagnostic, prognostic and monitoring tools for RA, and to provide insights into which modality can provide the optimal information for a desired outcome in a given clinical trial or practice situation. | |
| 21575746 | Immunosenescence and rheumatoid arthritis: does telomere shortening predict impending dise | 2011 Jul | The pathogenesis of RA, a disabling autoimmune disease, is incompletely understood. Early in the development of RA there appears to be loss of immune homeostasis and regulation, and premature immunosenescence. While identification of risk factors and understanding of the phases of RA pathogenesis are advancing, means of accurately predicting an individual's risk of developing RA are currently lacking. Telomere length has been proposed as a potential new biomarker for the development of RA that could enhance prediction of this serious disease. Studies examining telomere length in relation to RA have found that telomere erosion appears to proceed more rapidly in subjects with RA than in healthy controls, and that telomere lengths are shorter in those with the RA-risk HLA-shared epitope genes. These studies have been small, however, with retrospective or cross-sectional designs. The potential role of telomere shortening as an independent biomarker for future RA risk, perhaps strongly genetically determined by HLA-SE genes, after controlling for known risk factors such as smoking, body mass index and immunosuppressant medication use, as well as systemic inflammation, is an unanswered question. | |
| 21176800 | Current concepts in the treatment of rheumatoid arthritis of the distal radioulnar joint. | 2011 Feb | Rheumatoid arthritis (RA) may progressively affect all articulations of the wrist. Involvement of the distal radioulnar joint (DRUJ) is common and may be the first clinical signs of symptoms of RA. When the DRUJ is affected by RA, upper extremity function can be affected. Effective surgical management includes the Darrach procedure, the Suave-Kapandji procedure, the hemiresection interposition arthroplasty procedure and extensor tenosynovectomy. The long-term effectiveness of DRUJ arthroplasty is currently unknown. | |
| 22012611 | Interleukin-23 as a potential therapeutic target for rheumatoid arthritis. | 2012 Feb | Cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases, including rheumatoid arthritis (RA). Increasing evidence has revealed the importance of IL-23, which closely resembles IL-12 structurally and immunologically, in linking innate and adaptive immunity. IL-23, a newly identified heterodimeric pro-inflammatory cytokine, is composed of a p40 subunit in common with IL-12 and a unique p19 subunit. Recent evidence suggests that IL-23, rather than IL-12, is the crucial factor in the pathogenesis of various immune-mediated disorders. In addition, recent studies have explored the role of IL-23 in patients with RA. An elevated expression of IL-23 has been demonstrated in the synovial fibroblasts and plasma of patients with RA. Moreover, an association between IL-23 and IL-23R polymorphisms with susceptibility to RA has been reported. Therefore, the targeting of IL-23 or the IL-23 receptor has been proposed as a potential therapeutic approach for RA. In this review we will discuss the biological features of IL-23, and summarize recent advances in our understanding of the role of IL-23 in the pathogenesis and treatment of RA. | |
| 21718320 | FDG PET for rheumatoid arthritis: basic considerations and whole-body PET/CT. | 2011 Jun | [(18) F]Fluorodeoxyglucose (FDG) is a tracer for glucose metabolism. Its distribution is not specific to cancer cells but is also observed in inflammatory tissue, including macrophages, capillaries, and fibroblasts. Rheumatoid arthritis (RA) is a systemic, chronic inflammation of the joints resulting in synovitis. The disease is characterized by fibrovascular proliferation leading to the formation of a pannus and causing high FDG uptake. Several clinical studies of RA have demonstrated that FDG uptake in affected joints reflects the disease activity of RA, with strong correlations between uptake and various clinical parameters having been noted. Furthermore, the use of FDG PET for the sensitive detection and monitoring of the response to RA therapy has been reported. FDG PET/computed tomography (CT) enables the detailed evaluation of disease in large joints throughout the whole body, which is a unique advantage of PET/CT. FDG PET/CT can also be used to detect high-risk disease complications, such as atlanto-axial joint involvement, at an early stage. The possible contribution of FDG PET to the management of patients with RA remains to be studied in detail. | |
| 21468144 | Induction of immune tolerance in the treatment of rheumatoid arthritis. | 2011 May | Progress in our understanding of the genetics and immunology of rheumatoid arthritis (RA) has translated into clinical practice with the introduction of a first generation of biologic agents that effectively interfere with the inflammatory cascade by blocking a key component. This evolution has not only changed the way we practice, but perhaps also the way we think about RA and its treatment. In our view direct manipulation of specific pathogenic pathways is increasingly being used to replace generalized pharmacological immune suppression. The next leap forward will be to develop therapeutic approaches that will lead to maintenance of disease remission with a minimal-treatment or even drug-free regimen, relying on the induction of immune tolerance rather than the suppression of the immune system. Immune tolerance has the potential to prevent tissue damage secondary to inflammatory responses while at the same time maintaining homeostasis through physiologic recognition of self and the ability to perceive and react to 'danger'. Novel therapeutic approaches are emerging from these concepts. Such therapies will hopefully be safe and efficacious, and will complement the first generation of biologic agents that are currently available. | |
| 22891483 | [Genetic and environmental interactions on the development of rheumatoid arthritis]. | 2012 May | Rheumatoid arthritis (RA) more and more becomes a syndrome, rather than a disease, with genetic, hormonal and environmental influences, among which smoking and the microbiota generate focused interest. The shared epitope and PTPN22 loci are associated with RA, and, particularly, with the "classical" form with anti-citrullinated peptide antibodies (ACPA) and IgM-rheumatoid factor (IgM-RF) positivity. Pregnancy is associated with a--temporary--remission of RA. Epidemiological studies have shown that oral contraception, parity and hormonal replacement therapy influence the severity of RA, and, this is still discussed, its incidence. Smoking is the first environmental factor strongly associated with RA, specifically with the shared epitope and with ACPA. The study of the microbiota is a novel emerging field that will help us to better understand patterns and evolution of RA. | |
| 21539940 | The metabolic syndrome: the crossroads between rheumatoid arthritis and cardiovascular ris | 2011 Aug | Rheumatoid arthritis (RA) patients have an incidence of cardiovascular (CV) diseases at least two times higher than the general population. Atherosclerosis, the main determinant of CV morbidity and mortality, and carotid intima-media thickness, an early preclinical marker of atherosclerosis, also occur early on in RA. Traditional CV risk factors seem to have the same prevalence in RA and non-RA patients, and thus do not fully explain the increased CV burden, suggesting that RA inflammation and therapies play a role in increasing CV risk in these patients. The metabolic syndrome and fat tissue are likely to be the major players in this complex network. The metabolic syndrome (MetS) represents a cluster of cardiovascular risk factors that have in common insulin resistance and increased visceral adiposity. This entity has received great attention in the last few years due to its contribution to the burden of cardiovascular morbidity and mortality. Moreover, recently the adipose tissue has emerged as a dynamic organ that releases several inflammatory and immune mediators (adipokines). The association of MetS and atherosclerosis is thought to be partly mediated by altered secretion of adipokines by the adipose tissue and, on the other hand, there are evidence that adipokines may play some role in inflammatory arthritides. Obesity is now regarded as a systemic, low-grade inflammatory state, and inflammation as a link between obesity, metabolic syndrome, and cardiovascular diseases. To obtain a full control of the CV risk, data suggest that it is therefore mandatory a "tight control" of both RA and MetS inflammations. | |
| 21734327 | [Heat shock proteins in rheumatoid arthritis: friend or foe?]. | 2011 Jun 29 | Rheumatoid arthritis (RA) is one of the most common rheumatic diseases in the world. RA is a progressive and incurable systemic connective tissue disease with autoimmune background. Numerous reports indicate that the highly evolutionarily conserved heat shock proteins (HSP) are able to interact with the immune system. Recent research has shown that HSP play an important role in the regulation of chronic inflammation in RA, with the majority of information concerning the role of proteins belonging to the HSP70, HSP60 and HSP40 classes. This paper presents recent views on the role of HSP in the development of rheumatic diseases, as well as the potential for application of HSP in immunotherapy of patients suffering from RA. |