Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 18364173 | [Health-related quality of life of patients with rheumatoid arthritis. Which factors are o | 2008 Mar 3 | Rheumatoid arthritis (RA) is a chronic inflammatory disease causing joint pain, loss of function and decreased health-related quality of life (HRQoL). HRQoL in RA patients is associated with several risk factors; in this paper the evidence relating to the most important risk factors is reviewed. Modern medical therapy has improved HRQoL in RA patients, while demographic factors (female sex and older age), low socioeconomic status (in terms of education and position in the work force) and the presence of comorbid conditions appear to be associated with poorer HRQoL. | |
| 18219763 | The function of interleukin 17 in the pathogenesis of rheumatoid arthritis. | 2007 Sep | Interleukin (IL)-17 is a 30- to 35-kDa homodimeric polypeptide cytokine cloned in 1993 and originally named cytotoxic T lymphocyte-associated antigen-8 (CTLA-8). Sequencing the human genome resulted in the discovery of an additional five members of the IL-17 family that were consecutively named IL-17B to IL-17F. IL-17A is exclusively produced by a newly identified CD4+ T-helper subset that was recently named Th17. Differentiation of these cells from naive CD4+ T cells requires both TGF-beta and IL-6. IL-15 and, especially, IL-23 are required for these cells' survival and efficient IL-17 production. IL-17 binding to an IL-17 receptor expressed on epithelial, endothelial, and fibroblastic stromal cells triggers the activation of transcription factor NF-kappaB and mitogen-activated protein kinase (p-38), which in turn results in the secretion of IL-1, TNF-alpha, IL-6, IL-8, or prostaglandin E2. The IL-17 family plays a key role in the regulation of immune and inflammatory response, in the homeostasis of several tissues, and the progression of autoimmune diseases. In addition, IL-17 exerts synergistic effects with TNF-alpha and IL-1 in the induction of joint inflammation and cartilage and joint destruction. Given these properties, it is not surprising that in certain pathological conditions, for example rheumatoid arthritis, Th17 cells emerge as a new pathological cell type that, by IL-17 production and release, contributes to their pathogeneses. | |
| 17075600 | Monitoring disease activity of rheumatoid arthritis in clinical practice: contributions fr | 2006 Nov | Rheumatoid arthritis is a heterogeneous and progressive autoimmune disease, and patients with this condition show varied responses to treatment. Practical, reliable, individually tailored measures of disease activity and treatment responses are needed. Outcome measures used in randomized, controlled trials, including American College of Rheumatology response criteria and Disease Activity Scores, identify when treatment should be initiated or changed, but can be time consuming and impractical in daily practice. Simplified disease activity indices, abbreviated joint counts and patient-report questionnaires are more-convenient ways to assess therapeutic responses in the clinic. Patient-reported measures of physical function, pain and global disease activity best differentiate the results of active treatment from those of placebo treatment in randomized, controlled trials. Improvements in physical function closely reflect changes in health-related quality of life. Recent trials have demonstrated limited correlations between clinical responses and radiographically demonstrated responses; both should be assessed on a regular basis. It is recommended that three domains be assessed in the clinic for therapeutic responses: patient-reported measures of physical function and/or global disease activity; physician assessment of disease activity; and imaging of the hands and/or feet on a biannual basis. Problematic joints and cervical spine involvement should be followed as clinically indicated. Measures of improvement for individually relevant physical activities need to be defined for each patient. | |
| 17251223 | What effects might anti-TNFalpha treatment be expected to have on cardiovascular morbidity | 2007 Sep | Patients with rheumatoid arthritis (RA) have an increased burden of atherosclerotic cardiovascular disease which cannot be explained by an increased prevalence of traditional cardiovascular risk factors alone. Atherosclerosis is now being viewed as an inflammatory condition and the cumulative inflammation experienced in RA may contribute to accelerated atherosclerosis. It has been hypothesised that treatment with anti-tumour necrosis factor (TNF) alpha in RA may reduce both intra-articular inflammation and the inflammation associated with atherosclerosis. Thus, TNFalpha blockade may reduce the cardiovascular morbidity and mortality associated with RA. This review examines the pathophysiological role of TNFalpha in atherosclerosis and the evidence to date that anti-TNFalpha treatment modifies this process in RA. | |
| 18613841 | The role and therapeutic implications of fibroblast-like synoviocytes in inflammation and | 2008 Jun | Fibroblast-like synoviocytes (FLS) are resident mesenchymal cells of synovial joints that have been recognized to play an increasingly important role in the pathogenesis of rheumatoid arthritis (RA). Activation of FLS in the setting of RA leads to the production of a broad array of cell surface and soluble mediators that help to recruit, retain, and activate both cells of the immune system and resident joint cells, leading to the promotion of ongoing inflammation and tissue destruction. The ability of FLS to stimulate both inflammation and tissue damage suggests that this cell type may be a unique target for the treatment of inflammatory arthritis. Greater understanding of how FLS are activated and how they interact with other cells in the RA synovium may provide insights that allow development of novel agents for RA therapy. | |
| 17558653 | Anti-citrulline antibodies in the diagnosis and prognosis of rheumatoid arthritis: evolvin | 2007 | Citrulline is a non-standard amino acid that can be incorporated into proteins only by post-translational modification of arginine by peptidylarginine deiminase (PAD) enzymes during a variety of biologic processes, including inflammation. Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, with a prevalence of 0.3 to 1% worldwide, which leads to progressive joint erosion and substantial disability if not treated early. A reliable and specific test for a marker present early in the disease would be useful to identify RA patients prior to the occurrence of joint damage. A new group of autoantibodies, the anti-cyclic citrullinated peptide antibodies (anti-CCP), can be detected in up to 80% of patients with RA, are highly specific for the disease, and may be of value for both the diagnosis and the prognosis of RA. The fact that these antibodies may appear before the onset of the disease suggests a potential role in primary prevention. Interestingly, they may also play a role in the pathophysiology of this disabling disease. The process of citrullination, its physiologic role, and citrullination-related pathologies, as well as the use of anti-citrullinated protein antibody tests (ACPA) for the early diagnosis and prognosis of RA and their potential role in the pathophysiology of the disease, are discussed. | |
| 16920569 | Immunopathologic role of B lymphocytes in rheumatoid arthritis: rationale of B cell-direct | 2006 Aug | Although the immunopathogenesis of rheumatoid arthritis (RA) remains unclear, recent advances have paved the way for new therapies, such as anti-cytokine and cell-directed therapies. Here, B cells have re-gained interest concerning the pathogenesis of a number of autoimmune diseases after observing that patients with RA and non-Hodgkin lymphoma, who received anti-CD20 therapy leading to B cell depletion, demonstrated remarkable improvements. The underlying modes of action appear to be related to B cell functions, such as deletion of memory B cells, interruption of immune activation, antigen-presentation and production of inflammatory cytokines. In many RA patients, synovial extrafollicular germinal centers develop, where B cells play an intimate role in local inflammation and the generation of memory B cells and plasma cells. These local processes lead to activation of the immune system and ultimately to joint destruction in RA. Recent data demonstrating the clinical value of B cell depletion in refractory RA patients substantiate the notion that B cells are important players in the pathogenesis of the disease. Future studies should clarify which functions are affected by B cell depletion, providing the promise of new avenues to patient-tailored therapies. | |
| 16329045 | Expression and function of cell cycle proteins in rheumatoid arthritis synovial tissue. | 2006 Feb | Rheumatoid Arthritis (RA) is a chronic disease characterised by synovial lining hyperplasia and progressive destruction of joint tissues. Experimental data suggests that abnormal alterations in the expression of proteins involved in maintaining homeostatic control of the cell cycle is involved in disease progression in RA. By contributing to the overgrowth of synovial tissue, factors such as dysregulated proliferation or reduced apoptosis of cells can directly influence the pathological outcome of RA. | |
| 17150009 | Rituximab: novel B-cell depletion therapy for the treatment of rheumatoid arthritis. | 2006 Dec | Significant numbers of patients with rheumatoid arthritis (RA) suffer from disease that is refractory to both conventional therapy and newer biological agents such as TNF-alpha inhibitors. These patients may respond insufficiently, lose an effective response, develop toxicity or carry contraindications to such agents. Rituximab, a chimeric monoclonal antibody against CD20 that effectively depletes B cells in peripheral blood, has been licensed for the treatment of certain haematological malignancies for almost 10 years. B cells are now known to have multiple key roles in the pathogenesis of RA. Data is now available that indicates efficacy and safety of B-cell depletion with rituximab in the treatment of RA in a variety of patient groups. The clinical outcomes from these studies, together with its safety profile, have led to rituximab being licensed for the treatment of patients with RA who have failed to obtain benefit from anti-TNF-alpha agents. | |
| 17023257 | Systemic rheumatoid vasculitis: a review. | 2006 Oct | OBJECTIVES: To review the most recent information on the incidence, clinical course, pathology, pathogenesis, diagnosis, and treatment of rheumatoid vasculitis (RV), including the still scanty data on the use of biologics. METHODS: PubMed and MEDLINE databases (1950-2006) were searched for the key words "vasculitis" and "rheumatoid arthritis"; and "rheumatoid arthritis" and "extra-articular manifestations." All relevant articles in English and French were reviewed. Additional words used in follow-up research include "anti-TNF," "rituximab," "IL-1 receptor antagonists," and "CTLA-4 Ig," all in conjunction with "vasculitis." Pertinent secondary references were also retrieved. RESULTS: RV is an inflammatory condition of the small- and medium-sized vessels that affects a subset of patients with established rheumatoid arthritis (RA) (approximately 1 to approximately 5%). It has a vast array of clinical manifestations with a predilection for the skin (peripheral gangrene, deep cutaneous ulcers) and the peripheral nervous system (mononeuritis multiplex). Because of the lack of specific signs and symptoms, the diagnosis relies on the exclusion of other causes of similar lesions (diabetes, atherosclerosis, drug reactions, infection, neoplasias) and, ideally, on the histopathological demonstration of necrotizing vasculitis. Despite the availability of a host of promising new drugs for the treatment of RA, no clinical trials have tested their efficacy in RV; therefore, its management remains largely empirical. CONCLUSIONS: Although RV has apparently been decreasing over the last 2 decades, possibly as a consequence of the more energetic approach to the management of RA currently used, it remains an important complication of RA that needs to be promptly recognized and treated. | |
| 17290298 | PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and b | 2007 Mar | Dysregulated signal transduction in innate and adaptive immune cells is known to be associated with the development of various autoimmune and inflammatory diseases. Consequently, targeting intracellular signalling of the pro-inflammatory cytokine network heralds hope for the next generation of anti-inflammatory drugs. Phosphoinositide 3-kinases (PI3Ks) generate lipid-based second messengers that control an array of intracellular signalling pathways that are known to have important roles in leukocytes. In light of the recent progress in the development of selective PI3K inhibitors, and the beneficial effects of these inhibitors in models of acute and chronic inflammatory disorders, we discuss the therapeutic potential of blocking PI3K isoforms for the treatment of rheumatoid arthritis and other immune-mediated diseases. | |
| 18159206 | [Cystic Rheumatoid Arthritis--case report]. | 2007 Oct | Among the many radiological findings seen in Rheumatoid Arthritis RA small subchondral geodes and erosions are typical. Large geodes are far less common abnormalities and their presence may indicate diagnostic and therapeutic difficulties. We present a case report of a 55-year old woman with seronegative RA that developed a large geode in the knee with extensive joint destruction. | |
| 16932675 | Technology insight: gene transfer and the design of novel treatments for rheumatoid arthri | 2006 Mar | Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by systemic inflammation and joint destruction. Novel therapies have emerged during the past decade, marking a new era in the treatment of RA. Meanwhile, in vivo and in vitro gene-transfer studies have provided valuable insights into mechanisms of disease pathogenesis. Advanced gene-delivery techniques and animal models promise further progress in RA research and the development of novel therapeutic strategies for this disease. In this article we provide an overview of the wide spectrum of potential targets that have been identified so far, discuss currently available gene-transfer methods, and outline the barriers that need to be overcome for these approaches to be successfully applied in daily practice. | |
| 17635796 | Pathological survivin expression links viral infections with pathogenesis of erosive rheum | 2007 Aug | Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage and bone destruction. Insufficient apoptosis in the inflamed RA synovium along with accumulation of highly differentiated B- and T-lymphocytes as well as invasive growth of macrophages and fibroblasts is among the major mechanisms supporting joint destruction. We have recently shown that circulating survivin, an apoptosis inhibitor tightly bound to tumorigenesis, is an independent predictor of development and progression of joint destruction in RA. In this review we discuss the possible connectivity between viral infection, leading to interferon (IFN)-alpha production, survivin expression, and subsequent joint inflammation. The role of IFN-alpha and the involvement of IFN transcription factors and phosphoinositide-3-kinase signalling as essential modulators of arthritogenic process are discussed in the context of survivin. | |
| 18937635 | Limitations of a quantitative swollen and tender joint count to assess and monitor patient | 2008 | A quantitative count of swollen and tender joints is a primary measure to assess patients with rheumatoid arthritis (RA), and is weighted of higher value than the other 5 Core Data Set measures in all indices in which it is included. However a number of limitations of the swollen and tender joint count have been described in the rheumatology literature, including poor reproducibility, with a requirement to be performed by the same observer at each visit; likelihood to improve with placebo treatment as much or more than the other 5 RA Core Data Set measures in clinical trials; similar or lower relative efficiencies than global and patient measures to document differences between active and control treatments in clinical trials; improvement over 5 years in clinical care, while joint damage and functional disability may progress; and lower sensitivity to detect inflammatory activity than ultrasound. Most visits to a rheumatologist do not include a formal quantitative joint count. It may be suggested that a careful qualitative joint count, supplemented by quantitative patient self-report questionnaire scores, may be more than adequate to monitor and document changes in patient status in busy clinical settings. | |
| 16633925 | Potential impact of observational cohort studies in Japan on rheumatoid arthritis research | 2006 | For better management of rheumatoid arthritis (RA) patients, we need information both from well-designed clinical trials, such as randomized controlled trials, and from observational cohorts. Observational cohort study has not been developed in Japanese RA patients; however, two cohorts, IORRA (formerly J-ARAMIS) from 2000 and NinJa by iR-net from 2002, have been established. These two cohorts are an important source not only for better management of Japanese RA patients but also for solutions to a variety of issues concerning RA clinical practice in general. In this minireview, necessities of observational cohort studies are discussed. | |
| 17426357 | The immune response to citrullinated proteins in patients with rheumatoid arthritis: genet | 2007 Feb | This article reviews data concerning the applicability of anti-citrullinated peptide antibodies in the diagnosis, estimation of prognosis, and follow-up of patients with rheumatoid arthritis (RA). The production of anti-citrullinated peptide antibodies is closely associated with the presence of the HLA-DRB1 shared epitope, a known risk factor for development of RA, and the production may be influenced by environmental factors such as tobacco smoking. Patients who harbor this antibody from the early stage of their disease develop more severe erosive disease than patients with RA who lack the antibody. The anti-citrullinated peptide antibody level may be a reflection of disease activity, at least in the early phase of the disease. The antibody can sometimes be found several years before the onset of clinical symptoms of RA, which may represent an open window for preventive measures to be taken. | |
| 17684874 | Laryngeal involvement in rheumatoid arthritis. | 2007 Jun | Patient with rheumatoid arthritis should be screened prior to surgery for any laryngeal manifestation. A thorough history and physical examination coupled with indirect or direct laryngoscopy are mandatory. Nonspecific laryngeal symptoms in patients with rheumatoid arthritis should raise suspicion of laryngeal involvement. Phonatory disturbances or airway difficulties may reflect advanced stages of the disease. Their presence is usually coupled with high resolution computerized tomography findings. Aggressive therapy should be started and corticosteroid injection should be contemplated in cases of failure of conventional treatment. The anesthesiologist should handle with extreme care the inflamed laryngeal structures and be least aggressive in securing the airway. | |
| 18375533 | Reporting of patient-reported outcomes in recent trials in rheumatoid arthritis: a systema | 2009 Feb | OBJECTIVES: Patient-reported outcomes (PROs) have been increasingly recognised as important in rheumatoid arthritis (RA). The objective of this study was to assess the frequency of use of different PROs in recently published RA articles and to compare the tools used through a systemic literature review. METHODS: (1) DATA SOURCE: In PUBMED MEDLINE database, articles reporting any type of clinical study for adult patients with RA, published between February 2005 and February 2007, and reporting any type of PRO. Articles were excluded if they did not concern adult RA or if they did not report any PROs. (2) DATA EXTRACTION: demographic characteristics of patients, study design, treatment assessed and all PROs. (3) DATA ANALYSIS: descriptive. RESULTS: Of 109 reports, 50 (45%) were randomised controlled trials and 59 were other types of studies. A total of 63 questionnaires or tools for PROs were used, corresponding to 14 domains of health. Frequently reported domains (and most frequent tools) were: function, 83% (most frequent tool, health assessment questionnaire, HAQ); patient global assessment, 61% (most frequent tool, visual analogue scale, VAS); pain, 56% (VAS); and morning stiffness 27%. Domains such as fatigue, coping or sleep disturbance were infrequently reported. CONCLUSIONS: PROs are reported with great heterogeneity in recently published trials in RA. Some domains that appear important from the patient's perspective are infrequently reported. Further work is needed in this field. | |
| 17703178 | Contribution of genetic studies in rodent models of autoimmune arthritis to understanding | 2007 Oct | Rheumatoid arthritis (RA) is a chronic and potentially debilitating autoimmune disease. While novel therapies have emerged in recent years, disease remission is rarely achieved. RA is a complex trait, and the identifying of its susceptibility and severity genes has been anticipated to generate new targets for therapeutic intervention. However, finding those genes and understanding their function has been a challenging task. Studies in rodent intercrosses and congenics generated from inbred strains have been an important complementary strategy to identify arthritis genes, and understand how they operate to regulate disease. Furthermore, these new rodent arthritis genes will be new targets for therapeutic interventions, and will identify new candidate genes or candidate pathways for association studies in RA. In this review-opinion article I discuss RA genetics, difficulties involved in gene identification, and how rodent models can facilitate (1) the discovery of both arthritis susceptibility and severity genes, (2) studies of gene-environment interactions, (3) studies of gene-gender interactions, (4) epistasis, (5) functional characterization of the specific genes, (6) development of novel therapies and (7) how the information generated from rodent studies will be useful to understanding and potentially treating RA. |