Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
15885632 The fibroblast-like synovial cell in rheumatoid arthritis: a key player in inflammation an 2005 May Although multiple cell types are present in the rheumatoid joint, the fibroblast-like synovial cell (FLS) is among the most prominent. It is now appreciated that the FLS is not only space-filling, but is directly responsible for cartilage destruction, and also drives both inflammation and autoimmunity. In this article, we consider the normal role of the FLS in healthy joints, and review evidence that implicates the FLS as a central player in the propagation of rheumatoid arthritis.
17083758 Definitions of remission for rheumatoid arthritis and review of selected clinical cohorts 2006 Nov Various definitions of remission in rheumatoid arthritis (RA) have been proposed. The ACR (American College of Rheumatology--formerly ARA, American Rheumatism Association) remission criteria are strict and include nonspecific symptoms such as fatigue. More recently remission according to the Disease Activity Index (DAS) and DAS28 has been described. However, patients who meet the DAS28 remission cut point of < 2.6 may nonetheless have tender and/or swollen joints. The ACR remission criteria are more rigorous than the requirement of DAS28 <2.6. Newer tools for evaluation of RA activity include the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI), and cut points for remission according to these new indices have been defined. However, all available remission criteria may ignore important aspects of RA, including physical function and radiographic damage.
16398101 [The rheumatoid wrist]. 2005 Dec Wrist involvement in Rheumatoid Arthritis (RA) is frequent, variable in its presentation, heterogeneous in its evolution and has an important impact on the function of the affected hand. Surgery must be indicated within the framework of a structured medical and surgical approach that considers the whole patient. Surgical treatment at the wrist level is indicated in cases of resistant chronic pain, persistent articular synovitis, or chronic tenosynovitis and also in cases of painful limitation of supination, risk of complications due to wrist deformity and tendinous or neurological complications. The surgical goal in RA is to restore correct function but not neccessarily normal anatomy, with the goal of achieving a painless, stable wrist, correctly positioned. Motion depends on the status of the different joints and on the bone stock. Knowledge of the natural progression of the disease helps in the surgical decision making process. The pathogenesis and patterns of deformity, the clinical and X-ray appearances and the various techniques applied to the surgery of the rheumatoid wrist are studied and discussed including palmar wrist and dorsal wrist procedures, conservative and non-conservative options.
16736847 [Anti-CCP antibody test: diagnostic and pronostic values in rheumatoid arthritis]. 2006 Mar Rheumatoid arthritis is an auto-immune disorder which diagnosis is based on clinical, radiological and biological criteria. Disease progression is characterized by appearance of bone erosions and progressive articular deformations which attenuate functional mobility. Only rheumatoid factor is actually considered as biological factor among recognized diagnostical criteria despite its weak sensibility and specificity rates. Anti-cyclic citrullinated peptides antibodies are directed toward citrullinated isoforms of some filaggrin's epitopes. Their sensitivity and specificity reach respectively 80 and 99%. Their presence is correlated to disease activity and to bone erosions development. They allow early identification and treatment of rheumatoid arthritis affected patients which is actually considered as a priority.
16544923 [Rheumatoid arthritis: a general disease and local diseases]. 2005 Dec 15 The rheumatoid synovitis affects the joints by destroying the cartilage, the sub-chondral bone and the articular capsule. The tendons and ligaments can be degraded by proximity or by the means of the affected synovial sheaths. This conjunction of effects involves a foreseeable degradation on the complex articulations whose clinician must know the stages to interfere effectively into a preventive way by local interventions when the general treatments of the disease are insufficient and before recourse to the repairing surgery. This management can only be considered with a team where the general practitioner has a central place of alarm. Extraarticular symptoms (Sjogren's syndrome, cardiac, pulmonary or renal involvement) are specific local diseases and should be managed appropriately by the general practitioner and referred specialists.
16569368 The prevalence and clinical significance of antiphospholipid antibodies in rheumatoid arth 2006 Apr Published data were reviewed to evaluate the occurrence of antiphospholipid antibodies (aPL) in rheumatoid arthritis (RA) patients and to investigate their clinical relevance in this population. The mean prevalence was calculated at 28% and the median was 22%. Few studies have found a relationship between aPL antibodies and thrombosis, particularly in combination with other risk factors. Conflicting results have been reported on the association of anticardiolipin (aCL) antibody positivity and neurologic symptoms, Reynaud's phenomenon, disease activity, radiographic erosions, extra-articular RA manifestations, rheumatoid factor, and atherosclerosis. Some studies, however, suggest that there is a correlation present between those antibodies and C-reactive protein levels, rheumatoid nodules, and antinuclear antibodies. TNF-alpha blocking agents may cause an induction of aCL antibodies, but it seems like they do not cause any clinical features related to the antiphospholipid syndrome. Higher 17beta-estradiol levels were observed in aCL antibody-positive RA patients than in aCL antibody-negative patients and especially in premenopausal women, which may predispose to a more efficient immune response.
16237041 The devil in the details: the emerging role of anticitrulline autoimmunity in rheumatoid a 2005 Nov 1 Rheumatoid arthritis is a chronic inflammatory autoimmune disease of unknown cause. The immune response against citrullinated Ags has recently become the prime suspect for disease pathogenesis. Immunity against citrullinated Ags is thought to play a pivotal role in the disease for several reasons: 1) citrullinated Ags are expressed in the target organ, the inflamed joint; 2) anti-citrullinated protein Abs are present before the disease becomes manifest; and 3) these Abs are highly specific for rheumatoid arthritis. In this review, data from clinical, genetic, biochemical, and animal studies is combined to create a profile of this remarkable autoantibody response. Moreover, a model is proposed of how the anti-citrullinated proteins response is generated and how it could eventually lead to chronic inflammation.
17083764 Low disease activity state in rheumatoid arthritis: concepts and derivation of minimal dis 2006 Nov With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. MDA is between high disease activity and remission and anyone in remission will also be in MDA. This paper summarizes the process of coming to a definition of minimal disease activity in rheumatoid arthritis. Two equivalent preliminary definitions of minimal disease activity for use as secondary outcome measures in clinical trials in RA are proposed: a core-set definition based on the WHO/ILAR core set and a DAS-based definition based on the DAS28.
15589043 Does melatonin play a disease-promoting role in rheumatoid arthritis? 2005 Jan The pineal neurohormone melatonin (MLT) has been widely shown to exert an immunostimulatory and antiapoptotic role, mainly by acting on Th cells and on T and B cell precursors, respectively. Thus, MLT might favor or promote autoimmune diseases by acting directly on immature and mature immunocompetent cells. In fact, preclinical and clinical evidence point to a disease-promoting role of MLT in rheumatoid arthritis (RA). MLT, whose concentration is increased in serum from RA patients, may act systemically or locally in the inflamed joints. The circadian secretion of MLT with a peak level during the night hours might be strictly correlated with the peculiar daily rhythmicity of the RA symptoms. In rat studies employing Freund's complete mycobacterial adjuvant (FCA) as a model of rheumatoid arthritis, pinealectomized rats turned arthritic and exhibited a significantly less pronounced inflammatory response, which was restored to normal by a low MLT dose and was aggravated by a pharmacological MLT dose, that augmented the inflammatory and immune response. Continued investigation will refine our understanding of these observations, which will possibly translate into improved therapeutic approaches.
17157467 Abnormal electronystagmography in rheumatoid arthritis. 2007 Sep OBJECTIVE: Although sensorineural hearing loss has been widely investigated in those with rheumatoid arthritis, studies assessing the vestibular system in patients with rheumatoid arthritis are limited. The aim of this study was to assess the vestibular system in patients with rheumatoid arthritis. METHODS: The study consisted of 43 patients with rheumatoid arthritis and 30 healthy controls. Otorhinolaryngologic and neurotologic examinations, pure-tone audiometry, impedancemetry, electronystagmography including smooth pursuit, saccade, positional, and caloric tests were performed in all patients with rheumatoid arthritis and in controls. The erythrocyte sedimentation rate, C-reactive protein level, and rheumatoid factor level were evaluated in all patients with rheumatoid arthritis. RESULTS: Audiograms revealed sensorineural hearing loss in 12 patients (27.9%) with rheumatoid arthritis and in two controls (6.6%); the difference was statistically significant (P=.033). In those with rheumatoid arthritis, the results of electronystagmography revealed central abnormalities in nine patients (20.9%), peripheral abnormalities in three (6.9%), and mixed abnormalities in three (6.9%). Smooth pursuit and saccade tracing impairments were significantly higher in patients with rheumatoid arthritis (P>.05). Canal paresis in patients with rheumatoid arthritis were significantly higher than those in the control group (P=.039). No association was found between electronystagmographic abnormalities in patients with rheumatoid arthritis and age, sex, duration of disease, the results of laboratory testing, sensorineural hearing loss, or medication use. CONCLUSION: Our results suggest an association of rheumatoid arthritis with vestibular system dysfunction as well as auditory impairment.
17075600 Monitoring disease activity of rheumatoid arthritis in clinical practice: contributions fr 2006 Nov Rheumatoid arthritis is a heterogeneous and progressive autoimmune disease, and patients with this condition show varied responses to treatment. Practical, reliable, individually tailored measures of disease activity and treatment responses are needed. Outcome measures used in randomized, controlled trials, including American College of Rheumatology response criteria and Disease Activity Scores, identify when treatment should be initiated or changed, but can be time consuming and impractical in daily practice. Simplified disease activity indices, abbreviated joint counts and patient-report questionnaires are more-convenient ways to assess therapeutic responses in the clinic. Patient-reported measures of physical function, pain and global disease activity best differentiate the results of active treatment from those of placebo treatment in randomized, controlled trials. Improvements in physical function closely reflect changes in health-related quality of life. Recent trials have demonstrated limited correlations between clinical responses and radiographically demonstrated responses; both should be assessed on a regular basis. It is recommended that three domains be assessed in the clinic for therapeutic responses: patient-reported measures of physical function and/or global disease activity; physician assessment of disease activity; and imaging of the hands and/or feet on a biannual basis. Problematic joints and cervical spine involvement should be followed as clinically indicated. Measures of improvement for individually relevant physical activities need to be defined for each patient.
16164205 [Aetiology of rheumatoid arthritis]. 2005 Sep Although the aetiology of rheumatoid arthritis(RA) is still unclear, accumulating evidences are clarifying the involvement of genetic and environmental factors in the disease, or the pathogenic mechanism of perpetuating proliferative synovitis and bone destruction. Genetic factors including HLA-DR, PADI4, death receptor 3 or DEK were reported, whereas low concordance rate of RA in monozygotic twins or other evidences strongly imply the involvement of environmental factors in RA. Each constituents of RA synovium including macrophages, stromal cells, T cells and B cells, is shown to be involved in the aetiology of RA. Recently osteoclasts are shown to be mainly involved in the bone-destruction of RA. Clarification of RA aetiology will provide alternative in RA treatment especially for refractory RA.
15987499 Pathogenesis of rheumatoid arthritis: how early is early? 2005 Studies of cytokine expression in rheumatoid arthritis have provided key insights into the pathogenesis of disease and have offered clues for effective therapy. Patterns of T-cell products in chronic rheumatoid synovitis suggest that T helper type 1 cells contribute to the perpetuation of disease. However, there is no guarantee that the mechanisms of late disease are identical to very early rheumatoid arthritis. Evaluation of the cytokine profile at the earliest time points after onset of symptoms could identify novel targets that prevent progression to chronic arthritis.
15564308 X linked agammaglobulinaemia and rheumatoid arthritis. 2005 Jul BACKGROUND: Much interest has been shown recently in the pathogenic role of B cells in rheumatoid arthritis (RA) owing to the marked clinical responses to anti-CD20 treatment in RA. CASE REPORT: A patient with X linked agammaglobulinaemia (XLA) presented with an erosive symmetric polyarthritis with histological features of RA, including formation of a destructive pannus. Furthermore, the patient developed subcutaneous nodules that were histologically indistinguishable from rheumatoid nodules. Surprisingly, lymphocytic infiltrates in both the synovium and nodule consisted almost exclusively of CD8+ T cells. DISCUSSION: Although some peculiar B cell subsets have been described in patients with XLA, no B cell subsets could be demonstrated in synovial tissue or the subcutaneous nodule. This case illustrates that classical RA can develop in the absence of mature B cells.
16095003 Diagnostic and prognostic significance of autoantibodies in early rheumatoid arthritis. 2005 Mar A positive rheumatoid factor (RF) test has been included as one of the criteria for the diagnosis of rheumatoid arthritis (RA) according to the 1987 classification criteria of the American College of Rheumatology (ACR). During the past 20-30 years many different autoantibodies have been described in patients with RA. The presence of some of the autoantibodies in RA directed against various autoantigens, such as anti-neutrophil cytoplasmic antibodies, anti-nuclear antibodies, antibodies against interleukin-1 (IL-1), anti-cardiolipin antibodies, and antibodies against oxidized low density lipoprotein, is not specific for RA and these are not discussed here. This review summarizes the most relevant autoantibodies, and discusses their sensitivity, specificity, and possible diagnostic and prognostic significance in early RA. The antibodies are presented with the two clinically most relevant antibody tests first, followed by others in alphabetic order.
16920569 Immunopathologic role of B lymphocytes in rheumatoid arthritis: rationale of B cell-direct 2006 Aug Although the immunopathogenesis of rheumatoid arthritis (RA) remains unclear, recent advances have paved the way for new therapies, such as anti-cytokine and cell-directed therapies. Here, B cells have re-gained interest concerning the pathogenesis of a number of autoimmune diseases after observing that patients with RA and non-Hodgkin lymphoma, who received anti-CD20 therapy leading to B cell depletion, demonstrated remarkable improvements. The underlying modes of action appear to be related to B cell functions, such as deletion of memory B cells, interruption of immune activation, antigen-presentation and production of inflammatory cytokines. In many RA patients, synovial extrafollicular germinal centers develop, where B cells play an intimate role in local inflammation and the generation of memory B cells and plasma cells. These local processes lead to activation of the immune system and ultimately to joint destruction in RA. Recent data demonstrating the clinical value of B cell depletion in refractory RA patients substantiate the notion that B cells are important players in the pathogenesis of the disease. Future studies should clarify which functions are affected by B cell depletion, providing the promise of new avenues to patient-tailored therapies.
15660468 Assessing the safety of biologic therapies in rheumatoid arthritis: the challenges of stud 2005 Jan Clinical trials have shown the anti-tumor necrosis factor-a (TNF-a) drugs to be safe and efficacious for the treatment of rheumatoid arthritis (RA). However, since their release for general use, reports have raised concerns about potentially serious complications including tuberculosis, lymphoma, and cardiac failure. It must be remembered that patients with RA are already at increased risk of many of these complications,due both to their underlying inflammatory disease activity and the immunosuppressing effects of many conventional disease modifying antirheumatic drugs. It is unknown whether anti-TNF-a therapies are putting patients at increased risk of adverse events above what might already be expected. Data on the frequency of these adverse events have come predominantly from 3 sources: followup of subjects recruited to clinical trials, spontaneous adverse event reporting to national pharmacovigilance systems, and surveillance of patients treated in routine practice. Each of these study designs plays an important role in assessment of new drugs. However, each also has limitations, which must be considered when interpreting adverse event rates.
16329045 Expression and function of cell cycle proteins in rheumatoid arthritis synovial tissue. 2006 Feb Rheumatoid Arthritis (RA) is a chronic disease characterised by synovial lining hyperplasia and progressive destruction of joint tissues. Experimental data suggests that abnormal alterations in the expression of proteins involved in maintaining homeostatic control of the cell cycle is involved in disease progression in RA. By contributing to the overgrowth of synovial tissue, factors such as dysregulated proliferation or reduced apoptosis of cells can directly influence the pathological outcome of RA.
17150009 Rituximab: novel B-cell depletion therapy for the treatment of rheumatoid arthritis. 2006 Dec Significant numbers of patients with rheumatoid arthritis (RA) suffer from disease that is refractory to both conventional therapy and newer biological agents such as TNF-alpha inhibitors. These patients may respond insufficiently, lose an effective response, develop toxicity or carry contraindications to such agents. Rituximab, a chimeric monoclonal antibody against CD20 that effectively depletes B cells in peripheral blood, has been licensed for the treatment of certain haematological malignancies for almost 10 years. B cells are now known to have multiple key roles in the pathogenesis of RA. Data is now available that indicates efficacy and safety of B-cell depletion with rituximab in the treatment of RA in a variety of patient groups. The clinical outcomes from these studies, together with its safety profile, have led to rituximab being licensed for the treatment of patients with RA who have failed to obtain benefit from anti-TNF-alpha agents.
15945216 [Rheumatoid arthritis--new perspectives in its diagnosis]. 2005 May The early diagnosis of rheumatoid arthritis has ever been a challenge. The need of an early accurate and sensitive diagnostic have grown even more in the last few years since new data showed that an aggressive and early therapy may influence the course of RA and even remission may be achieved. Traditional and new diagnostic tools like ultrasound and MRI are reviewed and analysed in the perspective of early recognition of disease.