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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
16550339 Joint inflammation and cytokine inhibition in rheumatoid arthritis. 2006 Mar The hallmark of rheumatoid arthritis (RA) is chronic synovial inflammation resulting in progressive joint damage. Cytokines are key mediators of inflammation and can be found in abundance both in the joint and blood of patients with active disease. They are responsible not only for the destructive synovitis but also for some of the systemic features. Research over the last 2 decades has highlighted the important role of cytokines such as tumour necrosis factor alpha (TNF-alpha) and interleukins (IL) 1, 6 and 15 in the pathogenesis of RA and these are potential therapeutic targets. Inhibitors of TNF-alpha and IL-1 are already licensed treatments for RA. Novel biologic agents targeting IL-6 and -15 are currently being developed and showed promise in early clinical trials. This article reviews the role of various cytokines in the pathogenesis of RA and the therapeutic effect of inhibiting these cytokines.
16959892 Perioperative medication management for the patient with rheumatoid arthritis. 2006 Sep The treatment of rheumatoid arthritis has improved dramatically in recent years with the advent of the latest generation of disease-modifying antirheumatic drugs. Despite these advances, in some patients inflammation is not diminished sufficiently to prevent irreversible musculoskeletal damage, thus requiring surgical intervention to reduce pain and improve function. In these cases, the orthopaedic surgeon frequently encounters patients on a drug regimen consisting of nonsteroidal anti-inflammatory drugs, glucocorticoids, methotrexate, and biologic agents (disease-modifying antirheumatic drugs). Consultation with a rheumatologist is recommended, but the surgeon also should be aware of these medications that could potentially affect surgical outcome. Prudent perioperative management of these drugs is required to optimize surgical outcome. A balance must be struck between minimizing potential surgical complications and maintaining disease control to facilitate postoperative rehabilitation of patients with rheumatoid arthritis.
16137613 Anti-citrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis: specificity 2005 Sep Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific and sensitive markers for rheumatoid arthritis (RA). For instance, for the anti-CCP2 assay, sensitivities ranging from 55% to 80% and specificities ranging from 90% to 98% have been reported. Despite their high specificity, recent reports have suggested that ACPA may be found in some patients with other rheumatic autoimmune diseases, including psoriatic arthritis, systemic lupus erythematosus and Sjögren's syndrome. Also, the differences between the classical rheumatoid factor (RF) and ACPA, as well as the complementarity between both tests have recently been demonstrated more clearly. Indeed, both antibody systems have a different association with specific RA features like extra-articular manifestations, a different association with the HLA shared epitope and, behave differently following anti-TNF therapy.
17317617 The synovial membrane as a prognostic tool in rheumatoid arthritis. 2007 Mar The ability to effectively treat patients with rheumatoid arthritis (RA) has become increasingly feasible with the use of powerful treatment regimens early on in the disease. The use of such regimens has, however, created a pressing requirement for better prognostic markers to allow the targeting of these treatments to those most at need, hence minimizing expense and toxicity. As the synovial membrane has been ever more recognised as the primary pathogenetic site in RA its role as a prognostic indicator has been explored. As yet no reliable single prognostic marker has been identified. This article discusses the range of pathological variables already examined and those markers holding most potential.
15711233 Understanding functioning, disability, and health in rheumatoid arthritis: the basis for r 2005 Mar PURPOSE OF REVIEW: To examine the recent literature on rheumatoid arthritis in relation to functioning and disability, highlighting it from the perspective of the biopsychosocial model of functioning, disability, and health of the World Health Organization. This review focuses on longitudinal studies because they clarify associations found in cross-sectional studies and are useful in shedding light on the mechanisms that explain functioning and disability. RECENT FINDINGS: The studies that contribute best to understanding of functioning and disability in patients with rheumatoid arthritis are studies that (1) incorporate a comprehensive model to integrate different variables of interest, (2) use a longitudinal design to examine the potential casual relationships among the variables, and (3) use hierarchical regression analyses or path analysis to study the relation among variables. SUMMARY: It is time to rethink and redefine what should be measured when addressing functioning and disability of patients with rheumatoid arthritis. The use of a universally agreed framework and classification, such as the International Classification of Functioning, Disability and Health, a universally agreed-on comprehensive list of variables potentially relevant to functioning and disability in rheumatoid arthritis, and a greater focus on functioning-oriented versus disability-oriented perspectives constitute a solid foundation for such a rethinking process.
15797492 Selecting criteria for monitoring patients with rheumatoid arthritis. 2005 Mar Four treatment objectives govern the management of rheumatoid arthritis (RA): to control the clinical manifestations, to prevent structural damage, to prevent functional impairments, and to reduce excess mortality. Disease activity determines the extent of structural damage, the severity of functional impairments, and in part the excess mortality related to cardiovascular disease. In established RA, the functional impairments depend also on the extent of the structural damage. Methods for assessing disease activity, treatment responses, structural damage, and functional impairments are reviewed herein. A standardized follow-up protocol is suggested as a means of achieving greater uniformity in clinical practice.
17075189 [Approach from bedside to etiology/pathophysiology/treatment of rheumatoid arthritis]. 2006 Oct Rheumatoid arthritis (RA) is a disease full of variety. We need to elucidate various clinical doubts for the complete cure of RA. We observed a lot of patients with human parvovirus B19 (B19) infection who developed to RA till now. We investigated B19 infection in relation with RA etiology. B19 infects persistently to immune cells through cell surface Ku80 autoantigen as a cellular receptor. We are able to detect B19 in immune cells which infiltrate in synovial tissues of patients with RA. B19 is activated in infected cells, and functional viral protein NS1 induces over production of inflammatory cytokine TNFalpha. As a result, it promotes a neutrophile activation and migration to the synovium where there are B19-infected immune cells. This may cause arthritis and create a vicious circle of chronic inflammation that develops into RA. As for the B19 persistent infection to immune cells, abnormality of anti-B19 humoral immunity may participate in imperfection of B19 neutralization of a host. It is expected the development of effective treatment that cure progressing RA from B19 infection. NS1 may be one of the candidates of therapeutic target.
15720280 A role for the complement system in rheumatoid arthritis. 2005 The production of autoreactive antibodies from self-reactive B cells results in the formation of immune complexes that deposit in tissue and fix complement, contributing to the pathogenesis of rheumatoid arthritis (RA). Earlier mouse models emphasize the importance of autoreactive antibodies formed against "self" proteins that serve as a source for T cell-mediated immune response, stemming from cross-reactivity and resulting in B cell activity. However, more recent models suggest the need for both autoantibodies and the initiation of the inflammatory cascade via the alternative complement pathway, which is unbridled as the cartilage lacks the usual regulatory proteins of the complement system. Furthermore, deficiencies in specific complement proteins could lead to an escape from negative selection by these self-reactive B cells. Moreover, the classical complement pathway establishes chemotactic gradients by which inflammatory cells follow and accumulate in the synovial fluid where they engulf immune complexes and release proteolytic enzymes. In addition, the processing of circulating immune complexes either via Fc receptor or CR1 and opsonization by complement fragments plays a key role in determining the fate of immune status. In addition, complement proteins are a major determinant in the size and solubility of an immune complex, which also affects clearance. The evidence regarding intra-articular activation of the complement system in RA provides the possibility to pharmacologically manipulate various parts of the complement system for therapeutic purposes and potential therapeutic targets for the control of inflammation and the prevention of joint destruction.
17010589 Genes, environment and immunity in the development of rheumatoid arthritis. 2006 Dec The combined role of genes, environment and immunity in the development of rheumatoid arthritis (RA) has been the subject of recent investigations. New data support a gene-environment interaction between smoking and the MHC class II HLA-DRB1 shared epitope (SE) genes in anti-citrulline antibody (anti-CP(+)) RA but not in anti-CP(-) disease. These data from genetic epidemiology, together with information on citrullination in the lungs of smokers, have prompted the formulation of a new etiological hypothesis for anti-CP(+) RA, suggesting that smoking in the context of HLA-DR SE might trigger immunity to citrulline-modified proteins and that this immunity, after several years, might cause arthritis.
16884972 The history of bacteriologic concepts of rheumatic fever and rheumatoid arthritis. 2006 Oct OBJECTIVES: Review of the development of etiologic and pathogenetic concepts of rheumatic fever (RF) and rheumatoid arthritis (RA) from the beginning of clinical bacteriology to the discovery of antibiotics. METHOD: Analysis of English and German language publications pertaining to bacteriology and "rheumatism" between the 1870s and 1940s. RESULTS: Early in the 20th century there was a widely held belief that a microbial cause would eventually be found for most diseases. This encouraged pursuit of the intermittent findings of positive blood and synovial fluid cultures in cases of RF and RA. Development of a streptococcal agglutination test supported the erroneous belief that RA is a streptococcal infection, while the simultaneous development of other immunologic tests for streptococci suggested that a hemolytic streptococcus was etiologic in RF. Table 1 provides a chronology of major events supporting and retarding resolutions. CONCLUSIONS: Much of the conflicting data and inferences regarding the etiology of RF and RA can be attributed to the absence or inadequacy of controls in observations of clinical cohorts and laboratory experiments.
15639053 Estrogens and arthritis. 2005 Feb Sex hormones seem to play an important role as modulators and perpetuators of rheumatic disorders with autoimmune involvement, such as rheumatoid arthritis or systemic lupus erythematosus. Estrogens are implicated in the immune response as enhancers of the humoral immunity. Sex hormones can exert local actions (paracrine) in the tissues in which they are formed; an accelerated peripheral metabolic conversion of upstream androgen precursors to estrogens has been well-assessed. Local effects of sex hormones in autoimmune rheumatic diseases seem to consist mainly of the modulation of cell proliferation and cytokine production. All of these data further suggest caution in exogenous estrogen administration in patients who have autoimmune diseases.
16855149 Sex hormones and risks of rheumatoid arthritis and developmental or environmental influenc 2006 Jun Sex hormone relationships for onset risks of rheumatoid arthritis (RA) were analyzed in a nested case-control study, derived from a large community-based prospective cohort. A self-reported history of RA in a first-degree relative, heavy cigarette smoking, and positive rheumatoid factor (RF) were confirmed predictors of subsequent RA onset in this data set. In the 11 premenopausal onset cases, lower serum dehydroepiandrosterone sulfate levels were observed as was an imbalance in serum IL-1beta to IL-1ra levels; the latter was not observed in the 43 controls (CNs). In the 18 male cases, significantly higher serum cortisol was observed in the six cases with positive family history versus the 12 with a negative history. To the contrary, a small minority of the male cases had combined low serum cortisol and testosterone, which was not observed in the 72 CNs. Significant gender dimorphism was observed between the sex hormones and serum log RF titers as well as in the correlations of serum log testosterone and estradiol. Principal component analysis of multiply-imputed data sets extracted four uncorrelated components, which provided concordant neuroendocrine immune relationships to the previously investigated univariate and multivariate analyses. The literature on developmental and environmental influences on sex hormones and risks of RA was reviewed.
16082642 Interventions for foot disease in rheumatoid arthritis: a systematic review. 2005 Aug 15 OBJECTIVE: To systematically review medical and surgical foot intervention studies in rheumatoid arthritis (RA), focusing on clinical efficacy, study quality, and risk of harm. METHODS: We searched appropriate databases using a combination of the terms "rheumatoid arthritis" and "foot" against terms indicating treatment; we also hand-searched references. We selected articles in English (1968-2003) comprising randomized controlled trials (RCTs), controlled clinical trials (CCTs), prospective observational studies, and large retrospective observational surgical studies (> 50 cases). RCT quality was examined using Jadad scoring; other designs were assessed qualitatively. RESULTS: Inclusion criteria were met by 33 of 894 identified studies, comprising 5 RCTs and 1 CCT (all nonsurgical), 15 prospective observational studies (8 nonsurgical, 7 surgical), and 12 large retrospective studies (all surgical). Functional, custom-designed and semirigid orthoses and extra-depth shoes were effective in single RCTs of variable quality; no comparative studies have been conducted. This finding was supported by a CCT and prospective observational studies. There was no evidence of harm. There were no controlled trials of surgery. Prospective observational studies suggest that forefoot arthroplasty and first metatarsophalangeal joint implants, but not plantar callous debridement, are effective. Comparative retrospective analyses suggest that some procedure variants may be better, and surgery may relieve pain better than orthoses. Infection was the main risk. CONCLUSION: RCT evidence shows that orthoses and special shoes are likely to be beneficial in patients with RA. The only evidence of benefit from surgery comes from observational studies, because no RCTs have been conducted. Further RCT evidence is needed, although well-designed observational studies may be helpful.
16127011 Tumor necrosis factor inhibitor therapy for rheumatoid arthritis. 2005 Jun The immunopathology of rheumatoid arthritis (RA) is now better understood, and this knowledge has been translated into more effective therapy with biologic response modifiers. The first group of biologic response modifiers are the tumor necrosis factor inhibitors. There efficacy in controlling RA has been such that remission is now the goal of RA management. As with any patient treatment, safety is an issue; patients will need ongoing monitoring for infections, tumors, and other rare complications.
16918493 p38 mitogen-activated protein kinase (MAPK) in rheumatoid arthritis. 2006 Aug The importance of p38 MAPK inhibitors as new drug for rheumatoid arthritis is reflected by the large number of compounds that has been developed over the last years. In this review new insights such as non-stressful activation of p38 MAPK, and the role of p38 MAPK in regulation of NF-kappaB recruitment are also discussed.
15896730 Proteomic: new advances in the diagnosis of rheumatoid arthritis. 2005 Jul 24 BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting the joints. A number of novel treatment modalities have been introduced over the past years, and rheumatologists are now attempting to institute optimal treatment in recent-onset arthritis. To facilitate diagnosis during the early stages of disease, when often not all clinical symptoms are manifest, a good serological marker is needed. METHODS: Antibodies directed to citrullinated proteins provide this ability. The most sensitive assay for detecting these antibodies is the so-called anti-cyclic citrullinated peptide, second generation (CCP II) enzyme-linked immunosorbent assay (ELISA). RESULTS: The diagnostic and prognostic potential of anti-CCP antibodies and the availability of a fully automated assay method lead us to conclude that the test is satisfactory for routine use as a serological marker of RA. In addition, we consider the potential of multiplex autoantibody assays, including miniaturized, high-throughput microarray technology, to improve diagnosis and prognostication in early onset arthritis patients.
17106534 Rheumatoid arthritis, cytokines and hypoxia. What is the link? 2006 Nov Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that affects approximately 1% of the population, in a female to male ratio of 3:1. The disease can occur at any age, but it is most common among those aged 40-70 years. Despite many years of study, the etiology of RA is still undefined. However, with increased understanding of the immune system the pathogenesis of RA has become clearer. A large bulk of data suggests that T lymphocytes and macrophages play a critical role in the initiation and perpetuation of synovial inflammation. Recently, the cytokine profile of T helper cells has been associated with the disease, the cytokine repertoire of inflamed synovia is categorized as that of T helper 1 response. Moreover, in RA elevated levels of pro-inflammatory or inflammatory cytokines such as Tumor Necrosis Factor - alpha (TNF-alpha) and Interleukin -1 beta (IL-1beta) have been detected. Hypoxia up-regulates TNF-alpha and IL-1beta; therefore, considerable research interest has been focused on the biological consequences of the hypoxic nature of the rheumatoid synovium. Hypoxia might underlie the functional polarization of the T cells and cytokine production, and thus may contribute to the progression and persistence of the disease. In this short review, we discuss our current knowledge of the link between cytokines and RA and the role of hypoxia in the pathogenesis of the disease.
17049202 Treatment of early rheumatoid arthritis in developing countries. Biologics or disease-modi 2006 Dec Biologics are highly effective in the treatment of rheumatoid arthritis (RA), but they are very expensive. The costs of biologics should limit their usage in patients with RA, especially in the developing countries. Therefore, it is necessary to develop suitable strategies for treating RA patients in these countries. In this article, the efficacy, toxicity, and cost-effectiveness of conventional DMARDs and biologics will be investigated. The therapeutic strategies for treating early RA will also be proposed.
16274868 Management of the distal radioulnar joint in rheumatoid arthritis. 2005 Nov The DRUJ frequently is involved in RA and can be a source of major disability. Nonoperative treatment consists of adequate hand/occupational therapy, judicious splinting, and pharmacologic management. If unacceptable pain and dysfunction persists or if there is tendon rupture, surgery is indicated. Surgical treatment ranges from debridement and soft tissue balancing if the joint is preserved to osseous procedures ranging from Darrach resection, Sauve-Kapandji procedure, hemiresection, to distal ulna replacement. Tendon ruptures usually require tendon transfers. If an osseous procedure is required, the authors prefer the Sauve-Kapandji procedure in the younger, active adult. Darrach distal ulna resection is recommended for the older, sedentary patient. For either procedure, if there is evidence of pre-existing radiocarpal instability, partial or total wrist arthrodesis or arthroplasty should bea concomitant procedure.
15755408 Derangement, osteoarthritis, and rheumatoid arthritis of the temporomandibular joint: impl 2005 Apr Temporomandibular joint (TMJ) dysfunction is often believed to bea young person's malady. However, geriatric patients also present with clinical findings of TMJ clicking, locking, crepitation, limited opening, and pain. With our aging population and the high prevalence of rheumatic and musculoskeletal diseases in the elderly, it is important to understand the etiopathogenesis, clinical presentation, and management of derangement, rheumatoid arthritis, and osteoarthritis of the TMJ. Although arthritis of the TMJ usually causes only mild-to-moderate dysfunction in older patients, they present challenges related to medication use and comorbidity. This article presents the most recent understanding and therapeutic protocols for patient diagnosis and management.