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ID PMID Title PublicationDate abstract
16567358 Synovial fibroblasts: key players in rheumatoid arthritis. 2006 Jun Rheumatoid arthritis (RA) is a chronic autoimmune-disease of unknown origin that primarily affects the joints and ultimately leads to their destruction. The involvement of immune cells is a general hallmark of autoimmune-related disorders. In this regard, macrophages, T cells and their respective cytokines play a pivotal role in RA. However, the notion that RA is a primarily T-cell-dependent disease has been strongly challenged during recent years. Rather, it has been understood that resident, fibroblast-like cells contribute significantly to the perpetuation of disease, and that they may even play a role in its initiation. These rheumatoid arthritis synovial fibroblasts (RASFs) constitute a quite unique cell type that distinguishes RA from other inflammatory conditions of the joints. A number of studies have demonstrated that RASFs show alterations in morphology and behaviour, including molecular changes in signalling cascades, apoptosis responses and in the expression of adhesion molecules as well as matrix-degrading enzymes. These changes appear to reflect a stable activation of RASFs, which occurs independently of continuous exogenous stimulation. As a consequence, RASFs are no longer considered passive bystanders but active players in the complex intercellular network of RA.
18796279 [Smoking--a risk factor for rheumatoid arthritis development]. 2008 Sep 8 Rheumatoid arthritis (RA) is a chronic disabling inflammatory joint disease of unknown aetiology. Genetic and environmental factors are implicated in its pathogenesis. We performed a literature search on MEDLINE, the Cochrane database and EMBASE on the interaction between smoking and RA. It is concluded that previous and current smoking constitute a risk factor for RA development. Smoking acts synergistically with other RA risk factors, including IgM-rheumatoid factor, anti-CCP and shared epitopes. The effect of smoking on the course of RA has not been described in sufficient detail.
17083761 Remission and radiographic progression in rheumatoid arthritis. 2006 Nov Complete remission, defined as the presence of clinical as well as radiographic remission, is the ultimate goal of treatment of rheumatoid arthritis (RA). Functional disability in patients with low disease activity is associated with joint inflammation and joint damage. Despite the methodologic problems of scoring radiographs, studies show that radiographic progression is an important outcome measure, and conventional radiography remains the best available method to assess it. Whether radiographic progression is entirely dependent on the presence of joint inflammation is a matter of debate; some evidence suggests that radiologic progression may continue in patients who appear clinically to be in remission. The potential availability of more effective drugs in the near future presents a need to further define and monitor progression of joint damage by more reliable methods. Better diagnosis of joint damage will assist in our quest to attain and document full remission in RA. Some newer techniques that provide direct assessments of metabolic activity in the inflamed joint appear to predict radiographic progression before it can be detected by conventional methods. Until these techniques are validated and assessed for predictive value, we would advocate that radiographic progression be added to existing criteria for clinical remission, in order to define remission in RA more comprehensively.
16973111 Genetic markers of treatment response in rheumatoid arthritis. 2006 Oct Rheumatoid arthritis patients exhibit a considerable interindividual variability in response to drug treatment. Although many disease-related and demographic factors have been studied to predict treatment outcome, the effective disease-modifying antirheumatic drug (DMARD) therapy is not yet allocated based on factors that predict efficacy. Individual genetic characteristics are thought to play an important role in treatment response; therefore, current research aims to identify these genetic predictors for clinical response. Pharmacogenetic studies are beginning to provide results, which suggests that personalized treatment maximization of DMARD efficacy and minimization of adverse drug reactions are feasible.
17538565 Emerging targets of biologic therapies for rheumatoid arthritis. 2007 Jun Advances in molecular biology and the clinical success of strategies that target tumor necrosis factor (TNF) have led to further research into the pathophysiology of human rheumatoid arthritis. Several novel therapeutic targets have emerged from these efforts, including not only molecules that regulate TNF (e.g. TNF-alpha converting enzyme), the complex cytokine network (e.g. interleukin [IL]-6, IL-15, IL-17) and several adipokines, but also targets that originate from cellular and subcellular components of the disease. Strategies that aim at cellular targets include antibodies to CD20 or BLyS (also known as TNF ligand family member 13b), which deplete or inhibit B cells, as well as approaches that interfere with membrane-derived microparticles. Components of subcellular pathways, which are predominantly upstream of the central regulator of transcription nuclear factor kappaB, have also been studied. Of these, strategies that target mitogen-activated protein kinases have a leading role and are on the verge of clinical use; approaches that target specific molecules such as Janus kinases, signal transducer and activator of transcription proteins, and suppressor of cytokine signaling proteins also seem to show promise and might have a clinical application in the future.
18427163 Th17 cells and rheumatoid arthritis--from the standpoint of osteoclast differentiation--. 2008 Jun Rheumatoid arthritis is a chronic disease that affects multiple joints. It is considered to be an autoimmune disease in which a T helper (Th)-1 type response has been implicated to play an important pathogenetic role. As osteoclasts, cells that resorb bone, play a crucial part in the bone destruction that occurs in RA, we and others have investigated the pathophysiology of these cells. The findings that interferon (IFN)-gamma strongly inhibits osteoclastogenesis and that interleukin (IL)-17 has the ability to enhance osteoclast differentiation have cast doubt on the hypothesis that RA is a Th1 disease. In this review, I describe the relationship between Th cells, the so-called "commander" of the immune response, and RA, mainly from the viewpoint of the environments Th cells create for the excessive differentiation and function of osteoclasts, resulting in the destruction of bone.
17870030 Measuring disability and quality of life in established rheumatoid arthritis. 2007 Oct Rheumatoid arthritis is a chronic inflammatory disease with a major impact on physical and psychological health. It can cause severe disability and reduce health-related quality of life, aspects that are important to patients. Thus, it is important to measure disability and health-related quality of life in clinical practice and in clinical trials. This article presents an overview of the most important measures of outcome concerning disability and health-related quality of life, including different forms of the Health Assessment Questionnaire (HAQ, MHAQ, MDHAQ, HAQ II), visual analogue scales for fatigue and function, SF-36, Arthritis Impact Measurement Scales (AIMS/AIMS2), the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire, Nottingham Health Profile, Sickness Impact Profile and the utility instruments 15D, EQ-5D, SF-6D and Health Utilities Index (HUI) 2 and 3.
17083762 Is remission in rheumatoid arthritis associated with radiographic healing? 2006 Nov The precondition for joint damage in rheumatoid arthritis (RA) is inflammation, and the precondition for healing is absence of inflammation. A systematic search for healing phenomena in RA patients in remission has not yet been undertaken. In reports of patients in whom healing was observed, clinical and laboratory data have not been published in part due to space restrictions. However, this preliminary review of the existing literature about repair supports the thesis that a strong association may exist between remission and repair. Several reports indicate that patients in whom radiographic repair was seen were in clinical remission. In most reports clinical response to treatment was very good, and in groups of patients in which scoring was done, evidence of repair was seen in patients with strong inhibition or halt of radiographic progression. In contrast, healing is unlikely to be detected in patients with persistent clinically active disease and/or moderate or strong radiographic progression. In most reports clinical response to treatment was very good, and in groups of patients in which scoring was done, evidence of repair was seen in patients with strong inhibition or halt of radiographic progression. In contrast, healing is unlikely to be detected in patients with persistent clinically active disease and/or moderate or strong radiographic progression.
17968335 Mechanisms of disease: genetics of rheumatoid arthritis--ethnic differences in disease-ass 2007 Nov Large studies on the genetics of common rheumatic diseases, such as rheumatoid arthritis and systemic lupus erythematosus, have identified multiple polymorphisms related to disease susceptibility, including peptidylarginine deiminase 4 (PADI4) and protein tyrosine phosphatase N22 (PTPN22). Some of the identified genes are associated with multiple autoimmune disorders, and some seem to have unique associations with particular disease entities. Although the molecules encoded by these genes have a primary role in the molecular pathways of autoimmunity, genetic variations and contribution to disease susceptibility seem to vary between ethnic groups. In this Review, we report the findings on genes associated with rheumatoid arthritis and focus on the differences in the frequency of polymorphisms between various ethnic groups.
19022481 Systemic nonarticular manifestations of rheumatoid arthritis: focus on inflammatory mechan 2009 Oct OBJECTIVE: Extra-articular ("nonarticular") manifestations of rheumatoid arthritis (RA) are common and greatly affect physical and emotional health, as well as prognosis, including survival. Several plausible mechanisms have been advanced for many nonarticular manifestations but there is increasing evidence that pro-inflammatory cytokines (eg, tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1, and IL-6) are also involved. The purpose of this review is to provide a concise appraisal of recent studies investigating the involvement of inflammatory cytokines in the pathogenesis of nonarticular RA manifestations. METHODS: A Medline search for articles published between January 1995 and October 2007 was conducted using the following keywords: rheumatoid arthritis, anemia, cardiovascular, atherosclerosis, bone loss, osteopenia, osteoporosis, pulmonary, thrombocytopenia, lymphadenopathy, keratoconjunctivitis sicca, uveitis, scleritis, keratitis. The review focused on articles describing a potential role of inflammatory mediators in these conditions. RESULTS: Studies of many nonarticular manifestations strongly implicate pro-inflammatory cytokines and specific mechanisms by which these mediators are likely to act have even been elucidated. The inflammatory cytokines implicated are numerous but particularly include members of the TNF family and the interleukins, particularly IL-1 and IL-6. In bone loss, activated T-cells have been shown to express pro-inflammatory cytokines (eg, TNF, IL-1, IL-7, and IL-17) that differentially upregulate and downregulate mechanisms that mediate the balance between bone resorption and formation. Cytokine-mediated inflammation has also been implicated, for example, in the early stages of atherogenesis and this may explain the observed increase in cardiovascular disease among patients with RA. However, for some nonarticular manifestations, the association with pro-inflammatory cytokines has been less firmly established and potential mechanisms are more speculative. CONCLUSIONS: Overall, further research in this area will add to our understanding of the mechanisms of extra-articular manifestations in RA patients. These insights should allow clinicians to select therapies to better match the spectrum of joint disease and nonarticular manifestations in individual patients. This may be particularly relevant for newer biologic agents with specific inhibitory effects on cytokines such as TNF-alpha and IL-6.
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.
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.
18662304 Molecular aspects of rheumatoid arthritis: role of environmental factors. 2008 Sep Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease that affects 0.5-1% of the population. RA causes progressive joint destruction that leads to the restriction of activities of daily living and deterioration of quality of life. Although the pathogenesis of RA has not yet been fully elucidated, it is considered to be a complex, multifarious disease that is influenced by both genetic and environmental factors. Genetic influences that contribute to RA susceptibility have been demonstrated both in studies of twins and families, as well as in genome-wide linkage scans, and it is estimated that genetic factors are responsible for 50-60% of the risk of developing RA. Thus, environmental factors may explain the remaining risk of developing RA. A large variety of environmental factors such as infectious agents, smoking, sex hormones, pregnancy etc. have been extensively studied previously. Understanding of how these factors contribute to the development of RA may lead to the better understanding of pathogenesis of RA.
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.
18204994 Anaesthesiological problems in patients with rheumatoid arthritis undergoing orthopaedic s 2008 May The article presents anaesthesiological problems in patients with rheumatoid arthritis (RA) scheduled for orthopaedic surgeries. Organ changes due to RA and related treatment were taken into account. The anaesthetic techniques used for patients with RA underwent orthopaedic procedures were presented.
18334981 Surgery Insight: orthopedic treatment options in rheumatoid arthritis. 2008 May Longstanding rheumatoid arthritis (RA) leads to disability, caused mainly by joint destruction. The current goals of surgical intervention are to restore function and quality of life, prevent joint deterioration, relieve pain, and correct deformity. A number of different surgical treatment options are available to patients with RA, including synovectomy, arthrodesis, joint replacement, and soft tissue and special hand surgery; nonoperative management is also important. Decision-making and timing for orthopedic intervention are complex issues because of polyarticular involvement. Functional impairment, pain, and the subsequent loss of quality of life and inability to work have become the main considerations for surgical reconstruction. Early referral for orthopedic treatment can lead to improved functional benefit for patients with RA. The decision for orthopedic intervention should be established by an interdisciplinary team that includes rheumatologists and orthopedic surgeons experienced in the surgery of RA. Priority should be given to the joint that causes the greatest disability and pain. Disease progression and pharmaceutical treatment options should be taken into consideration when establishing an orthopedic intervention protocol.
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.
18422470 Cardiovascular risk in rheumatoid arthritis: effects of anti-TNF drugs. 2008 May BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of atherosclerotic cardiovascular disease which cannot be explained by traditional cardiovascular risk factors alone. Atherosclerosis is considered an inflammatory condition and inflammation experienced in RA may contribute to accelerated atherosclerosis. Thus, it should be hypothesized that treatment with antitumor necrosis factor alpha (anti-TNF-alpha), TNF-alpha being a pivotal component of the inflammatory cascade, may decrease concomitantly intra-articular inflammation and vessel inflammation. OBJECTIVE: The purpose of this review is to examine the data regarding cardiovascular mortality and morbidity in RA and the evidence available to date evaluating the influence of anti-TNF-alpha treatments in RA on the occurrence of cardiovascular events, on surrogate markers of atherosclerosis and classical cardiovascular risk factors. METHODS: Clinical trials, original studies and review articles were identified from a Medline search (1998 - December 2007). Articles in English were reviewed, with emphasis on those containing assessments of cardiovascular effects (i.e., biological, structural, clinical) of anti-TNF-alpha drug. CONCLUSION: The suppression of systemic inflammation favoring atherosclerosis may lead to an improvement in cardiovascular prognosis in inflammatory disorders. Thus, reduction of inflammatory joint disease in RA with anti-TNF-alpha therapy, as probably with any powerful disease-modifying antirheumatic drugs, seems to be, at least in part, associated with concomitant reduction of the risk of cardiovascular events.
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.
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.