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ID PMID Title PublicationDate abstract
18466466 Using the maternal-fetal genotype incompatibility test to assess non-inherited maternal HL 2007 Non-inherited maternal antigens encoded by specific HLA-DRB1 alleles (NIMA) have been implicated as a rheumatoid arthritis (RA) risk factor. Using genotype data from North American Rheumatoid Arthritis Consortium study participants and the maternal-fetal genotype incompatibility (MFG) test, we find evidence for offspring allelic effects but no evidence for NIMA as a RA risk factor. We discuss possible reasons why our result conflicts with several previous studies (including one of our own) that used RA patients from northern Europe.
18696089 [Adult onset Still's disease]. 2008 Sep Adult onset Still's disease is a rare, febrile, multisystem rheumatic disease with unknown etiology, which runs an intermittent course and can either go into remission after months to years or progress to a chronic course with substantial joint destruction. The prevalence of this disease has been increasing in the last decade presumably caused by better diagnostic tools but also by a higher awareness among physicians taking care of patients with "fever of unknown origin". This review is intended to augment this trend, since research on the role of proinflammatory cytokines in this disease has led to an improved diagnostic and therapeutic repertoire over the last few years. Ferritin and interleukin-18 serum levels are valuable diagnostic parameters and blockade of interleukin-1, interleukin-6, and tumor-necrosis-factor alpha can effectively control the inflammatory activity of this disease in most cases and also in life-threatening conditions.
16761498 The role of epithelial cells in the initiation and perpetuation of autoimmune lesions: les 2006 Sjögren's syndrome (SS) is a chronic autoimmune disease affecting epithelial tissues. Exocrine glands are the primary target and their functional impairment comes as a result of immune attack of epithelial cells of the affected organs (autoimmune epithelitis). In this interplay, the role of the epithelial cell is pivotal. Extensive data point to an intrinsically activated status. Moreover, the epithelial cells possess all the features needed in order to act as non-professional antigen presenting cells. Through apoptosis and exosomes release endocellular antigens contributing to tolerance breakdown. In addition, produce cytokines and chemokines that recruit lymphocytes in the immunopathogenic lesion. Herein, we review all the aforementioned aspects of the epithelial activity that lead to the perpetuation of the lesion as well as the probable viral factors for the intrinsic activation. Finally, we propose a model for SS pathogenesis that integrates the knowledge accumulated during the last decade.
18622932 [Sjögren's syndrome]. 2008 May The leading symptoms of this autoimmune disease are xerostomia and xerophthalmia. Both are characterised by a lymphoplasmacellular destructive inflammation of salivary and lacrimal glands and the detection of autoantibodies against Ro/SS-A and La/SS-B nuclear antigens. In the long run of the disease, a polyclonal hypergammaglobulinemia is evolving as a consequence of chronic B-cell stimulation which can also lead to B-cell lymphoma which underlines the need for periodical clinical and laboratory examinations. Further extraglandular manifestations of the disease are non-erosive polyarthritis, serositis, leukocytoclastic cutaneous vasculitis and polyneuropathy, which make a clear differentiation from different forms of autoimmune connectivitis even more difficult, in particular if sicca syndrome is also present which may represent a secondary Sjögren's syndrome. The treatment is mostly symptomatic and immunosuppressive drugs are only given in case of severe and life-threatening organ involvement.
16427379 Pathogenesis of hemophilic arthropathy. 2006 Jan Intra-articular bleeding is the most common clinical manifestation of hemophilia, and can adversely affect joints and lead to arthropathy. Affected joints are associated with changes to the synovium, bone, cartilage and blood vessels. Iron plays a critical role in the pathogenesis of this condition, and may exert its effects through a variety of different mechanisms. Hemophilic arthropathy shares some injury characteristics with rheumatoid arthritis, although the degree of analogy is a matter of some debate. The influences of the mechanisms underlying joint inflammation are better understood for rheumatoid arthritis than for hemophilia, and it is hoped that this knowledge can be used to provide a more comprehensive knowledge of the pathological process of hemophilic arthropathy. This, in turn, may enable novel targets for therapeutic intervention to be identified.
20528400 Pharmacoeconomics of adalimumab for rheumatoid arthritis, psoriatic arthritis, ankylosing 2008 Apr Adalimumab is a monoclonal antibody that inhibits TNF, an osteogenic cytokine involved in the pathogenesis of chronic, disabling inflammatory diseases. Adalimumab is indicated for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease. It alleviates the symptoms of these diseases, prevents disease progression in some patients and, in the case of Crohn's disease, induces and maintains remission. Compared with traditional disease-modifying antirheumatic drugs that offer significantly less benefit, adalimumab is much more costly. However, most studies to date demonstrate the cost-effectiveness of adalimumab treatment. Cost-effectiveness data for newer indications of adalimumab, including ankylosing spondylitis and Crohn's disease, are needed. As longer term data for adalimumab become available, the cost-effectiveness data will have greater precision.
18261383 [Prognosis of patients with primary Sjögren's syndrome]. 2008 Feb 2 The natural history of primary Sjögren's syndrome has been little studied. Some studies agree that, although it is not a benign disease, it is characterized by a steady evolution of the predominant symptoms (sicca and general manifestations). However, there are 2 main exceptions to this chronic course: the development of vasculitic manifestations, and the high incidence of lymphomas, both processes being related to the excess of mortality in patients with primary Sjögren's syndrome. Recent studies have prospectively analyzed the outcome of this disease in a large series of patients and identified those factors present at diagnosis prospectively associated with an adverse outcome. The main prognostic factors identified are severe involvement of the exocrine glands, vasculitis, hypocomplementemia and cryoglobulins at diagnosis. These features identify a specific subset of patients diagnosed with primary Sjögren's syndrome in whom a closer follow-up, and probably an earlier and more robust therapeutic management, should be mandatory.
16949136 Pathogenesis and management of adult-onset Still's disease. 2006 Dec OBJECTIVE: To review recent literature regarding the pathogenesis and treatment of adult-onset Still's disease (AOSD). METHODS: We searched MEDLINE and PUBMED from 1971 to present using the following terms: adult-onset Still's disease, AOSD, or adult Still's disease. In addition we manually retrieved relevant abstracts from recent American College of Rheumatology and European League Against Rheumatism meetings. RESULTS: The etiology of AOSD, a rare, immune-mediated, multisystem inflammatory disorder characterized by quotidian spiking fevers, evanescent rash, and arthritis, remains unknown. An infectious etiology has been postulated, although a definitive agent has yet to be identified. Cytokines, such as interleukin (IL)-1, IL-6, interferon (IFN)-gamma, and tumor necrosis factor-alpha, are elevated in patients with AOSD. IL-18 and macrophage-colony stimulating factor also seem to play a role. Treatment historically consisted of nonsteroidal antiinflammatory drugs, often in combination with low-dose corticosteroids. Immunosuppressants (mainly methotrexate, but also intramuscular gold, azathioprine, cyclosporine A, leflunomide, and cyclophosphamide) and intravenous gamma-globulin are efficacious and have been used as steroid-sparing drugs. The recently reported use of anticytokine (anti-TNF-alpha, anti-IL-1, and anti-IL-6) agents in refractory cases has opened new horizons in the treatment of AOSD and provided important clues for its pathophysiology. CONCLUSIONS: Advances in immunology have enhanced our understanding of the role of cytokines in AOSD pathogenesis. Early, promising studies of anticytokine agents in AOSD may provide further insight into the pathogenetic mechanisms of this complex disease.
18984411 Pulmonary manifestations of primary Sjögren's syndrome. 2008 Nov Sjögren's syndrome (SS) is a systemic disease with a predilection for the exocrine glands. It also is considered to be an autoimmune epitheliitis, and, as the respiratory system is lined throughout with epithelial cells, it should not be surprising that patients who have SS may develop pulmonary disease. This article describes these manifestations.
19069959 Serum melatonin in juvenile rheumatoid arthritis: correlation with disease activity. 2007 May 1 The study was conducted to investigate the abnormalities in early morning serum melatonin among patients with Juvenile Rheumatoid Arthritis (JRA) and to outline its relation to disease activity and severity. Twenty one patients with JRA and twenty healthy age and sex matched controls were enrolled in the study. Fifteen patients had polyarticular JRA, 3 had oligoarticular and 3 had systemic onset JRA. Evaluation was carried out clinically, functionally and radiologically by using disease activity score, Juvenile Arthritis Functional Assessment Report for Children (JAFAR-C score) and modified Larsen score, respectively. Laboratory investigations included Complete Blood Picture (CBC), The Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), classic IgM Rheumatoid Factor (RF), Anti-nuclear Antibodies (ANA) and melatonin estimation in serum. The serum levels of melatonin were significantly increased in JRA patients (mean +/- SD = 13.9 +/- 8 pg mL(-1)) as compared to healthy controls (mean +/- SD = 8.1 +/- 2.7 pg mL(-1), p < 0.01). A significant positive correlation could link serum melatonin levels to disease activity scores and ESR (r = 0.91, p < 0.001 and r = 0.55, p < 0.01, respectively). No significant correlation was found between melatonin and either Larsen or JAFAR scores (r = 0.19, r = 0.15, respectively). According to melatonin levels, there were 2 groups of patients: Group I with elevated melatonin level (more than 11 pg mL(-1)) (n = 15) and group II with normal melatonin level (less than 11 pg mL(-1)) (n = 6). Patients with elevated melatonin levels had higher ESR (p < 0.05), higher disease activity scores (p < 0.01) and Larsen scores (p < 0.05), than the group of patients with normal serum melatonin. The results of GAFAR scores were comparable between the two groups (p > 0.05). Hence the study conclude that the elevated melatonin levels among JRA patients with active synovitis and its close relation to disease activity rather than disease severity suggests that melatonin might play a promoting role in rheumatoid arthritis. Hence, inhibition of its synthesis and/or action by specific antagonists may be of therapeutic value.
20496444 2007 Jan Targeted immune modulators are used in the treatment of certain types of immunologic and inflammatory diseases, including rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), plaque psoriasis, Crohn's disease, and ulcerative colitis (UC). These drugs work by selectively blocking mechanisms involved in the inflammatory and immune response. The purpose of this review is to help policy makers and clinicians make informed choices about the use of targeted immune modulators.
18214500 [Significance of clinically latent bacterial arthritis]. 2008 Feb The classical septic bacterial arthritis is a rare event, but can be distinguished by unequivocal signs such as fibrin exudation and neutrophilic masses (pus). For a long time we have been observing an abortive form of bacterial arthritis in biopsies which subsides spontaneously without antibiotic intervention. Only very early during the course can Staphyolcoccus aureus or epidermidis be detected. Despite the brief presence of bacteria, enzymes from the neutrophils can destroy cartilage and bone. The fact that the attending physician had suspected a bacterial infection in only 7% of these patients highlights the diagnostic complexity. We have termed this form clinically latent bacterial arthritis (CLBA). Structural changes in the synovial membrane, e.g. in rheumatoid arthritis or osteoarthritis, predispose for a hematogenous seeding of endogenous staphylococci and trigger clinically unapparent, temporary infections. This clinically latent bacterial superinfection (CLSI) is also self-limiting, but the high degrading potential of the neutrophilic proteases makes CLSI a very probable contributing factor in joint destruction.
17767747 Vasculitis: mechanisms involved and clinical manifestations. 2007 Systemic vasculitis, an inflammatory necrotizing disease of the blood vessel walls, can occur secondary to autoimmune diseases, including connective tissue diseases. Various pathogenic mechanisms have been implicated in the induction of vasculitis, including cell-mediated inflammation, immune complex-mediated inflammation and autoantibody-mediated inflammation. This inflammatory activity is believed to contribute to accelerated atherosclerosis, and also leads to increased risk for cardiovascular events in patients with rheumatoid arthritis and systemic lupus erythematosus. Endothelial cell activation is a common pathogenic pathway in the systemic vasculitis associated with rheumatoid arthritis and systemic lupus erythematosus, with elevated levels of endothelin-1 potentially inducing vascular dysregulation.
19804006 The use of antirheumatic disease drugs during pregnancy. 2006 Nov Many connective tissue diseases occur more frequently in women, the female:male ratio for systemic lupus erythematosus is 9:1 and for rheumatoid arthritis is 3:1. These diseases frequently afflict young women, many of whom wish to become mothers. While some diseases (for example, rheumatoid arthritis) generally improve during pregnancy, other immune-mediated diseases may be exacerbated by pregnancy, putting both the mother and fetus at risk and making control of maternal disease a top priority. This review examines the current literature pertaining to the use of antirheumatic drugs during pregnancy, including aspirin and nonsteroidal anti-inflammatory drugs, corticosteroids, anticoagulants, the 4-aminoquinoline antimalarial drugs, immunomodulating drugs, antimetabolite drugs and other agents including sulfasazine and anticytokine therapy.
16380240 Chemokines and leukocyte trafficking in rheumatoid arthritis. 2006 Feb 21 Leukocyte infiltration into the joint space and tissues is an essential component of the pathogenesis of rheumatoid arthritis (RA). In this review, we will summarize the current understanding of the mechanisms of leukocyte trafficking into the synovium, focusing on the role of adhesion molecules, chemokines, and chemokine receptors in synovial autoimmune inflammation. The process by which a circulating leukocyte decides to migrate into the synovium is highly regulated and involves the capture, firm adhesion, and transmigration of cells across the endothelial monolayer. Adhesion molecules and chemokine signals function in concert to mediate this process and to organize leukocytes into distinct structures within the synovium. Chemokines play a key regulatory role in organ-specific leukocyte trafficking and activation by affecting integrin activation, chemotaxis, effector cell function, and cell survival. Consequently, chemokines, their receptors, and downstream signal transduction molecules are attractive therapeutic targets for RA.
18789135 Magnet therapy for the relief of pain and inflammation in rheumatoid arthritis (CAMBRA): a 2008 Sep 12 BACKGROUND: Rheumatoid arthritis is a common inflammatory autoimmune disease. Although disease activity may be managed effectively with prescription drugs, unproven treatments such as magnet therapy are sometimes used as an adjunct for pain control. Therapeutic devices incorporating permanent magnets are widely available and easy to use. Magnets may also be perceived as a more natural and less harmful alternative to analgesic compounds. Of interest to health service researchers is the possibility that magnet therapy might help to reduce the economic burden of managing chronic musculoskeletal disorders. Magnets are extremely cheap to manufacture and prolonged treatment involves a single cost. Despite this, good quality scientific evidence concerning the safety, effectiveness and cost-effectiveness of magnet therapy is scarce. The primary aim of the CAMBRA trial is to investigate the effectiveness of magnet therapy for relieving pain and inflammation in rheumatoid arthritis. METHODS/DESIGN: The CAMBRA trial employs a randomised double-blind placebo-controlled crossover design. Participant will each wear four devices: a commercially available magnetic wrist strap; an attenuated wrist strap; a demagnetised wrist strap; and a copper bracelet. Device will be allocated in a randomised sequence and each worn for five weeks. The four treatment phases will be separated by wash out periods lasting one week. Both participants and researchers will be blind, as far as feasible, to the allocation of experimental and control devices. In total 69 participants will be recruited from general practices within the UK. Eligible patients will have a verified diagnosis of rheumatoid arthritis that is being managed using drugs, and will be experiencing chronic pain. Outcomes measured will include pain, inflammation, disease activity, physical function, medication use, affect, and health related costs. Data will be collected using questionnaires, diaries, manual pill counts and blood tests. DISCUSSION: Magnetism is an inherent property of experimental devices which is hard to conceal. The use of multiple control devices, including a copper bracelet, represents a concerted attempt to overcome methodological limitations associated with trials in this field. The trial began in July 2007. At the time of submission (August 2008) recruitment has finished, with 70 trial participants, and data collection is almost complete. TRIAL REGISTRATION: Current Controlled Trials ISRCTN51459023.
21794424 [The B cell in the pathogenesis of rheumatoid arthritis]. 2007 Jul Classically, B-cells have been considered to play a secondary role in the pathogenesis of rheumatoid artritis, restricted to the production of auto-antibodies. Nevertheless, the unexpected good clinical response that the systemic depletion of B-cells has demonstrated in a well-controlled clinical trial in patients with rheumatoid artritis has revitalized the interest in this cell type in the pathogenesis of this autoimmune disease. Several evidences suggest that B-cells can regulate the course of the immune response through antibody productionindependent mechanisms. These mechanisms include antigen presentation and the release of soluble factors such as proinflammatory cytokines, metalloproteinases, and chemokines. This article reviews experimental data supporting that the participation of B-cells in the pathogenesis of rheumatoid arthritis occurs through multiple mechanisms.
16501594 Macrophage activation syndrome and other systemic inflammatory conditions after BMT. 2006 Apr Autologous hematopoietic cell transplantation (HCT) is being used to treat autoimmune diseases refractory to conventional therapy, including rheumatoid arthritis. Macrophage activation syndrome (MAS) is a descriptive term for a systemic inflammatory disorder that has been described in patients with juvenile rheumatoid arthritis (JRA). This case report describes a young adult with systemic JRA (sJRA) who developed MAS on day # 12 post-autologous transplantation. The patient developed high fever, laboratory evidence of disseminated intravascular coagulation (DIC), hepatocellular injury, pancytopenia and hyper-ferritinemia. All viral, bacterial and fungal studies were negative and the patient improved with high-dose glucocorticosteroid and cyclosporine therapy. Extreme elevation of serum ferritin was documented and helpful in monitoring response to therapy. A number of systemic inflammatory syndromes have been described in association with HCT. These include DIC, 'engraftment syndrome,' infection-associated hemophagocytic syndrome and familial hemophagocytic lymphohistiocytosis. Macrophage activation syndrome presents with features of DIC and is closely related or identical to infection-associated hemophagocytic syndrome. The diagnosis needs to be established in a timely fashion because early and appropriate treatment may improve outcome.
17967186 Collagen-induced arthritis in C57BL/6 mice is associated with a robust and sustained T-cel 2007 Many genetically modified mouse strains are now available on a C57BL/6 (H-2b) background, a strain that is relatively resistant to collagen-induced arthritis. To facilitate the molecular understanding of autoimmune arthritis, we characterised the induction of arthritis in C57BL/6 mice and then validated the disease as a relevant pre-clinical model for rheumatoid arthritis. C57BL/6 mice were immunised with type II collagen using different protocols, and arthritis incidence, severity, and response to commonly used anti-arthritic drugs were assessed and compared with DBA/1 mice. We confirmed that C57BL/6 mice are susceptible to arthritis induced by immunisation with chicken type II collagen and develop strong and sustained T-cell responses to type II collagen. Arthritis was milder in C57BL/6 mice than DBA/1 mice and more closely resembled rheumatoid arthritis in its response to therapeutic intervention. Our findings show that C57BL/6 mice are susceptible to collagen-induced arthritis, providing a valuable model for assessing the role of specific genes involved in the induction and/or maintenance of arthritis and for evaluating the efficacy of novel drugs, particularly those targeted at T cells.
18078633 Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate in juvenil 2007 Sep OBJECTIVE: To compare serial C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels in juvenile rheumatoid arthritis (JRA) patients and investigate their application as diagnostic parameters and prognostic predictive factors. METHODS: We carried out retrospective chart review among JRA patients who were followed-up at the National Taiwan University Hospital (NTUH) between 1994 and 2005. RESULTS: Thirty-nine girls and 68 boys were included in this study. At the time of diagnosis, the prevalence of ESR was significantly greater than that of CRP (86.8% vs. 47.2%, p < 0.05). ESR revealed more responsiveness to treatment compared to CRP (SRMs were -0.69 and -0.31, respectively). At the time of diagnosis, high CRP levels (>or= 5mg/dL) correlated with poor therapeutic response, as do positive CRP (> 0.8 mg/dL) and high ESR levels (> 40 mm/h) after treatment for six months. Overall, initial high CRP levels (>or= 5mg/dL) demonstrated the strongest predictive role of failure of the first remission. CONCLUSION: For disease diagnosis, ESR can be a better parameter than CRP but a high initial CRP level can strongly predict treatment failure of the first remission.