Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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20528498 | Outcomes associated with early rheumatoid arthritis. | 2006 Oct | Rheumatoid arthritis is a common disease affecting 1% of adults in the UK and western countires. No single outcome measure comprehensively captures the full range of potential outcomes in early rheumatoid arthritis, so a range of measures are needed. This article evaluates the clinical and economic outcomes of early rheumatoid arthritis. These include pain, which is a major concern for patients, fatigue and persisting disease activity. The key therapeutic goal - remission of these clinical features - is achieved by 10-36% of early rheumatoid arthritis patients using currently available treatment. Disability, erosive damage and work disability are other important negative outcomes of early rheumatoid arthritis. Together, they account for its high direct and indirect medical costs. These various outcomes are outlined in this article. | |
20477047 | Adalimumab for early rheumatoid arthritis. | 2008 Mar | Rheumatoid arthritis affects 1% of the population and can result in joint destruction, reduced quality of life and function, loss of work productivity and, in severe cases, early mortality. Recent advances with optimal therapeutic strategies, including early initiation of treatment, tight control of the disease activity aiming for remission of the disease and the advent of biological therapies, have led to improved outcomes for patients with rheumatoid arthritis. It is generally agreed that the best outcomes for patients with rheumatoid arthritis occur when treatment is started early. Adalimumab is a new fully humanized monoclonal antibody that blocks the adverse effects of excess TNF-alpha. New studies using this agent early in the course of rheumatoid arthritis indicate superior rates of remission for patients with this disease. | |
23105718 | Lipid peroxidation and antioxidant status in patients with rheumatoid arthritis. | 2008 Jan | The changes in the erythrocyte lipid peroxidation products (MDA), levels of glutathione (GSH), ascorbic acid and plasma vitamin E (non enzymatic antioxidant parameters) and activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GP(X)), catalase in erythrocytes and plasma glutathione - S - transferase (GST) activity were estimated in patients with rheumatoid arthritis. This work was undertaken to assess oxidative stress and anti oxidant status in patients with rheumatoid arthritis. It was observed that there was a significant increase in erythrocyte MDA levels, activities of SOD, GP(X), plasma GST and a significant decrease in erythrocyte GSH, ascorbic acid, plasma vitamin E levels and catalse activity in patients with rheumatoid arthritis when compared to controls. The results of our study suggests higher oxygen free radical production, evidenced by increased MDA and decreased GSH, ascorbic acid, vitamin E and Catalase activity, support to the oxidative stress in rheumatoid arthritis. The increased activities of antioxidant enzymes may be a compensatory regulation in response to increased oxidative stress. | |
23105613 | Positive influence of Methotrexate-Hydroxychloroquine combination on the expression of GM- | 2006 Sep | Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) has been inducted as a mediator of inflammation in rheumatoid arthritis. Methotrexate combination therapy forms an important component of the treatment regimen in rheumatoid arthritis. The present study was undertaken to evaluate the influence of Methotrexate-Hydroxychloroquine (MTX-HCQ) combination and Sulfsalazine- Hydroxychloroquine (SSZ-HCQ) combination on the expression GM-CSFR in neutrophils isolated from synovial fluids. 15 cases of confirmed rheumatoid arthritis patients who presented at the hospital for surgical correction of joint deformities were selected for the study. Neutrophils isolated from the synovial fluids were used as the source of the receptor for quantitation on an enzyme immunoassay (EIA). The EIA was developed and standardized in our laboratory for quantification of the GM-CSF R. The findings are suggestive of the fact that the administration of MTX-HCQ combination has positive influence on the expression of the GM-CSF R on neutrophils as against SSZ-HCQ combination. The physiological basis of this increase needs further investigation. | |
18786965 | IL-6 trans-signalling directly induces RANKL on fibroblast-like synovial cells and is invo | 2008 Nov | OBJECTIVES: We investigated the influence of cytokines on the expression of RANK ligand (RANKL) in fibroblast-like synoviocytes from RA patients (RA-FLS). METHODS: RA-FLS were stimulated by IL-6, TNF-alpha, IL-17 and IL-1beta with or without soluble IL-6 receptor (sIL-6R) for 24 h. The expression of RANKL was measured by real-time PCR, western blotting and immunostaining. In proliferation assay, RA-FLS were cultured with cytokines for 3 days. RA-FLS were co-cultured with RAW cell in the presence of IL-6/sIL-6R for 3 days and then NFATc1 mRNA expression in RAW cells was examined. RA-FLS was cultured with parthenolide [PAR, signal transducer and activator of transcription (STAT) inhibitor] or PD98059 (PD, mitogen-activated protein kinase inhibitor) in the presence of IL-6/sIL-6R and then the influence of these drugs on phosphorylation of STAT3 and ERK1/2, and RANKL expression was examined. RESULTS: RANKL expression was induced by IL-6/sIL-6R (but not IL-6 alone) and by IL-1beta. On the other hand, TNF-alpha and IL-17 did not induce RANKL expression, although TNF-alpha, IL-17 or IL-1beta stimulated cell growth and IL-6 production. However, in the presence of sIL-6R, TNF-alpha or IL-17 induced RANKL expression. By the co-culture of RA-FLS, NFATc1 mRNA expression was induced in RAW cells. Finally, IL-6/sIL-6R induced phosphorylation of STAT3 and ERK1/2 in RA-FLS, and was completely inhibited by PAR and PD, respectively. PAR completely inhibited IL-6/sIL-6R-induced RANKL expression, but PD did not. CONCLUSIONS: IL-6/sIL-6R directly induced RANKL expression in RA-FLS and it is essential for RANKL induction by TNF-alpha and IL-17. Moreover, RANKL induction by IL-6/sIL-6R is mediated by the janus kinase/STAT signalling pathway. | |
18836242 | Evidence for species differences in the regulation of MMPs by all-trans retinoic acid in c | 2008 | In inflammatory conditions, chondrocytes produce large amounts of matrix metalloproteases (MMP) and nitric oxide (NO) thought to contribute to joint degradation. We tested the ability of all-trans retinoic acid (ATRA, a retinoic acid receptor (RAR) agonist) to modulate these inflammatory genes in chondrocytes from humans or rats, chosen as representative of animal models of arthritis. All RAR subtypes and RXR-alpha or -beta were expressed at the mRNA level in both species, although IL-1beta (10 ng/ml) inhibited RAR subtypes more markedly in rat than in human cells. ATRA (300 or 1000 nM) inhibited IL-1-induced expression of iNOS and nitrites level in both species, although the NO pathway was induced maximally in rat cells. ATRA displayed controversial effects on MMPs between rat and human chondrocytes, especially for MMP-9 expression. The effects of ATRA were irrelevant to the nuclear translocation of AP-1. The present data underlines that retinoids have a species-dependent impact on IL-1-induced responses in chondrocytes, suggesting that extrapolation of their pharmacological properties from animal cells has a poor relevance to clinical situation. | |
27732364 | Rheumatoid arthritis in practice Peter Taylor Rheumatoid arthritis in practice The Royal S | 2007 Feb 1 | The concise, relatively small book is an excellent resource for aspiring or established nurse specialist or advanced practitioners and prescribers who are interested in evidence based care of the individual with rheumatoid arthritis. However, there are one or two caveats to recommending this book. Firstly it fails to describe the full benefits of key roles that nurses and multi-professional teams play - although these are briefly discussed it will not give the reader enough information about the scope of each individual role. In addition, the social and psychological impact of the condition is not really considered in this book. So these issues and aspects of managing symptoms and supporting the individual with rheumatoid arthritis are sadly lacking and the reader would need to other key nursing textbooks to compliment this otherwise excellent book. | |
21886713 | Fixed drug eruption followed by lichen aureus during abatacept add-on therapy of rheumatoi | 2008 Dec 27 | BACKGROUND: Abatacept is a soluble fusion protein approved as add-on drug in rheumatoid arthritis. MAIN OBSERVATIONS: Here we report the first case of fixed drug eruption followed by lichen aureus due to abatacept in a 67-year-old woman. CONCLUSION: Fixed drug eruption is an unexpected drug reaction for abatacept, since T-cell activation is inhibited. | |
17957371 | The potential utility of B cell-directed biologic therapy in autoimmune diseases. | 2008 Jan | Increasing awareness of the importance of aberrant B cell regulation in autoimmunity has driven the clinical development of novel B cell-directed biologic therapies with the potential to treat a range of autoimmune disorders. The first of these drugs-rituximab, a chimeric monoclonal antibody against the B cell-specific surface marker CD20-was recently approved for treating rheumatoid arthritis in patients with an inadequate response to other biologic therapies. The aim of this review is to discuss the potential use of rituximab in the management of other autoimmune disorders. Results from early phase clinical trials indicate that rituximab may provide clinical benefit in systemic lupus erythematosus, Sjögren's syndrome, vasculitis, and thrombocytopenic purpura. Numerous case reports and several small pilot studies have also been published reporting the use of rituximab in conditions such as myositis, antiphospholipid syndrome, Still's disease, and multiple sclerosis. In general, the results from these preliminary studies encourage further testing of rituximab therapy in formalized clinical trials. Based on results published to date, it is concluded that rituximab, together with other B cell-directed therapies currently under clinical development, is likely to provide an important new treatment option for a number of these difficult-to-treat autoimmune disorders. | |
16462444 | Inflammatory arthritides of the spine: surgical versus nonsurgical treatment. | 2006 Feb | Ankylosing spondylitis and rheumatoid arthritis are disorders that cause marked alterations in the structure and function of the axial skeleton. Ankylosing spondylitis causes calcification of spinal structures causing limited motion. Rheumatoid arthritis causes synovial hypertrophy, joint destruction, and spinal instability. Surgical therapy for patients with ankylosing spondylitis corrects angular deformities with spinal osteotomies, and stabilization for spinal fractures. Spinal operative therapy for rheumatoid arthritis concentrates on correction of abnormal motion in the cervical spine. Advances in the medical therapy of spondyloarthritis have resulted in control of the inflammation of the axial skeleton halting the damage to spinal structures. The new biologic therapies for ankylosing spondylitis prevent progression of disease. Similarly, these same biologic therapies can also control the progression of rheumatoid arthritis including the cervical spine. The new medical therapies are very effective in preventing joint damage. The need for surgical intervention for patients with ankylosing spondylitis and rheumatoid arthritis will become a rare event in the setting of the new medical therapies for these inflammatory arthropathies. | |
18472730 | [Adult-onset Still's disease]. | 2008 Mar 19 | If the diagnosis of Adult-onset Still disease is often entertained, the disease remains difficult to diagnose in the absence of any specific clinical or laboratory anomaly. Diagnosis is still a diagnosis of exclusion, and the difficulty rests in the rational and appropriate use of those exclusion tests. Treatment is pragmatic, based on an analysis of the situation and a clear definition of the objectives. Finally, if biological treatments appear efficient, they should be reserved for patients resistant to conventional therapy or corticodependant. | |
18662412 | Septic arthritis in patients with rheumatoid arthritis. | 2008 Jul 29 | There is an increasing number of rheumatoid patients who get septic arthritis. Chronic use of steroids is one of the important predisposing factors. The clinical picture of septic arthritis is different in immunocompromised patients like patients with rheumatoid arthritis. The diagnosis and management are discussed in this review article. | |
20477671 | Outcome measures in rheumatoid arthritis: the OMERACT process. | 2007 May | The development of valid outcome measures is essential for appropriate management of any condition, but particularly chronic rheumatic diseases, such as rheumatoid arthritis. Over the last 15 years, Outcome Measures in Arthritis Clinical Trials has been dedicated to developing such measures in a variety of musculoskeletal conditions, including rheumatoid arthritis, osteoarthritis, osteoporosis, ankylosing spondylitis and gout. | |
18476458 | Coexistence of systemic sclerosis, scleroderma-like syndromes and neoplastic diseases. | 2008 Mar | Coexistence of rheumatic and neoplastic diseases may take different forms. Rheumatic paraneoplastic syndromes, including systemic sclerosis, scleroderma-like changes and Raynaud's phenomenon are induced by substances secreted by neoplastic cells and immunological disturbances connected are associated with malignancy. They may precede the clinical manifestation of neoplasm, occur simultaneously or after its diagnosis. In turn, chronic course of rheumatic diseases (Sjögren's syndrome, systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis) by immunologic stimulation may promote carcinogenesis. Genetic, environmental factors (viruses, chemical substances, radiation) and alterations of immunological surveillance may be the cause of both rheumatic and paraneoplastic disorders. Anticancer therapy may cause rheumatic diseases and immunosuppressive agents used in patients with rheumatic syndromes may have carcinogenic effect. Patients with long-standing or atypical course of rheumatic disorders, positive family or personal history of neoplastic disease, positive cancer markers, monoclonal antibodies or presence of other paraneoplastic syndromes should be diagnosed as possibly having occult neoplasm. In this paper we reviewed available literature on coexistence of rheumatic processes and malignancies to attract particular attention to practical aspects of this vital issue. | |
17958024 | [Early rheumatoid arthritis (ERA) diagnosis]. | 2007 Sep | The rheumatoid arthritis (RA) diagnosis is based on the ARA criteria, even though the radiological joint erosions are often a requirement to make a definite diagnosis. The early rheumatoid arthritis (ERA) concept was thought of following the poor therapeutic response of the established RA. The "window of opportunity" is defined as a time frame in the early phase of the disease in which the therapeutic response is favoured, and thus giving a real chance to modify the course and the prognosis of RA. To achieve such a goal, new imaging modalities have been developed (MRI and Musculoskeletal ultrasonography--MSU), together with new serologic, inflammatory markers, genetic tests and taking into account the environmental impact (such as tobacco smokers). Such an issue can be achieved with a tight collaboration between the primary care physician and the rheumatology speciality care. | |
16219707 | Diagnosis and management of adult onset Still's disease. | 2006 May | BACKGROUND: Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown aetiology that is responsible for a significant proportion of cases of fever of unknown origin and can also have serious musculoskeletal sequelae. OBJECTIVE: To assess and synthesise the evidence for optimal diagnosis and management of AOSD. METHODS: The key terms, adult onset Still's disease, AOSD, adult Still's disease, ASD, Still's disease were used to search Medline (1966-2005) and PubMed (1966-2005) for all available articles in the English language. Clinically relevant articles were subsequently selected. Bibliographies, textbooks, and websites of recent rheumatology conferences were also assessed. RESULTS: Data on diagnosis and treatment of AOSD are limited in the medical literature and consist mainly of case reports, small series, and modest scale retrospective studies. Diagnosis is clinical and requires exclusion of infectious, neoplastic, and other autoimmune diseases. Laboratory tests are non-specific and reflect heightened immunological activity. Treatment comprises non-steroidal anti-inflammatory drugs, corticosteroids, immunosuppressive drugs (methotrexate, leflunomide, gold, azathioprine, cyclosporin A, cyclophosphamide), and intravenous gammaglobulin. The recent successful application of biological agents (anti-tumour necrosis factor, anti-interleukin (IL)1, anti-IL6), often in combination with traditional immunosuppressive drugs, has been very promising. CONCLUSIONS: AOSD often poses a diagnostic and therapeutic challenge and clinical guidelines are lacking. The emergence of validated diagnostic criteria, discovery of better serological markers, and the application of new biological agents may all provide the clinician with significant tools for the diagnosis and management of this complex systemic disorder. | |
20477085 | Leflunomide in the treatment of rheumatoid arthritis. | 2006 Jan | Rheumatoid arthritis is a chronic and highly morbid disease affecting approximately 1% of the world's population. With the advent of disease-modifying antirheumatic drugs, patients are increasingly able to maintain control of their arthritis and prevent joint destruction. However, not all patients respond adequately to any single disease-modifying antirheumatic drug, and many newer parenteral therapies are cost prohibitive. Leflunomide, an inhibitor of pyrimidine biosynthesis, is the first oral disease-modifying antirheumatic drug to have been approved for rheumatoid arthritis in the USA in the last 15 years, and is now widely used in over 70 countries around the world. Leflunomide is efficacious when used as monotherapy or in combination with methotrexate to treat patients with rheumatoid arthritis, and is generally well tolerated. As clinical use increases, new ways to use leflunomide in order to minimize toxicity and maximize efficacy are being explored. | |
18466462 | Application of bivariate mixed counting process models to genetic analysis of rheumatoid a | 2007 | We sought to i) identify putative genetic determinants of the severity of rheumatoid arthritis in the NARAC (North American Rheumatoid Arthritis Consortium) data, ii) assess whether known candidate genes for disease status are also associated with disease severity in those affected, and iii) determine whether heterogeneity among the severity phenotypes can be explained by genetic and/or host factors. These questions are addressed by developing bivariate mixed-counting process models for numbers of tender and swollen joints to evaluate genetic association of candidate polymorphisms, such as DRB1, and selected single-nucleotide polymorphisms in known candidate genes/regions for rheumatoid arthritis, including PTPN22, and those in the regions identified by a genome-wide linkage scan of disease severity using the dense Illumina single-nucleotide polymorphism panel. The counting process framework provides a flexible approach to account for the duration of rheumatoid arthritis, an attractive feature when modeling severity of a disease. Moreover, we found a gain in efficiency when using a bivariate compared to a univariate counting process model. | |
18466443 | One- and two-locus models for mapping rheumatoid arthritis-susceptibility genes on chromos | 2007 | To evaluate whether there is evidence for two rheumatoid arthritis (RA) susceptibility genes on chromosome 6, we applied new robust methods for two-locus multipoint identical-by-descent mapping to the rheumatoid arthritis data of the Genetic Analysis Workshop 15. The software GEEARP was used to estimate the locations and the corresponding genetic effects for one locus or two linked loci in a region on chromosome 6, on the basis of affected relative pairs. These methods were applied to the data sets from the North American Rheumatoid Arthritis Consortium, Canada, France, and the first screen of United Kingdom. From the resultant 95% confidence intervals given by a robust variance estimator, a linked region, other than the well-known HLA region, was at 54.7-69.6 cM, providing evidence for a second rheumatoid arthritis susceptibility locus on chromosome 6. | |
18342072 | [Interstitial granulomatous dermatitis with arthritis: four cases]. | 2008 Jan | BACKGROUND: Interstitial granulomatous dermatitis with arthritis, or Ackerman's syndrome, is characterized by inflammatory articular flares of potentially destructive outcome and cutaneous lesions of varied patterns: cord-like lesions on the flanks or violaceous plaques on the trunk and limbs. Histologically, the main features are histiocytes laminated between collagen fibres, sometimes organized in rosettes comprising tiny granulomas surrounding fibres of homogeneous aspect. CASE REPORTS: Four patients fitting this description were investigated. Cutaneous lesions displayed various patterns: cord-like lesions (one patient), brown plaques on the flanks edged with papules (one patient), grossly annular violaceous plaques on the back (one patient), and infiltrated plaques on the palms and thighs (one patient). Joint symptoms were present in all cases (one seropositive rheumatoid arthritis and one seronegative rheumatoid arthritis, both already known; acute rheumatoid arthritis in two cases). The histological pattern was quite similar in all cases, with laminated histiocytes in palisading layers mixed with swollen collagen fibres; "rosette" figures were present in two cases. Autoimmune response was seen with antinuclear antibodies (two cases) and/or rheumatoid factor (two cases). The short-term outcome of cutaneous lesions was rapidly favourable in most cases with systemic steroids (one case) or Non Steroidal Anti-Inflammatory Drugs (one case), and spontaneously in one case. COMMENTS: This entity, defined by the presence of inflammatory arthritis and cutaneous lesions of various clinical types, either more specific but infrequent (cord-like), or less specific but more frequent (plaque-like), and featuring a peculiar histological pattern, chiefly affects women aged between 30 and 80 years. Pathophysiological mechanisms and nosological borders are debatable and authors consider this condition as either an autonomous disease or else a mere subset of vasculitis with palisading granulomas in collagen vascular disorders, despite the rarity of authentic vasculitis. A setting of autoimmunity is frequently present. Furthermore, a fairly similar histological pattern is sometimes seen in some lesions forming a subset of cutaneous side-effects of drugs. Articular outcome may be unfavourable with joint destruction in more than half of patients, whether or not in a setting of rheumatoid arthritis. Spontaneous resorption can occur. Treatment has not yet been codified and is based primarily on anti-inflammatory drugs. |