Browse

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

ID PMID Title PublicationDate abstract
18952639 Orthopaedic surgery in 255 patients with inflammatory arthropathies: longitudinal effects 2009 Oct OBJECTIVE: To examine the effectiveness of orthopaedic surgery in patients with inflammatory arthropathies with regard to longitudinal changes in pain, physical function and health-related quality of life and explore differences in effectiveness between replacement versus non-replacement surgery and surgery in the upper versus the lower limb. METHODS: 255 patients (mean age 57.5 years (SD 13.1), 76.7% female) with inflammatory arthropathies underwent orthopaedic surgical treatment and responded to mail surveys at baseline and during follow-up (3, 6, 9 and 12 months). The booklet of questionnaires included the arthritis impact measurement scales 2 (AIMS2), health assessment questionnaire (HAQ), short form 36 (SF-36), EQ-5D and visual analogue scales (VAS) addressing patient global, fatigue, general pain and pain in the actual joint. Standardised response means (SRM) were calculated to estimate the magnitude of improvement. RESULTS: Significant improvement was seen for most of the dimensions of health, the largest improvement for pain in the actual joint (SRM 1.17) at one year follow-up. SRM for AIMS-2 physical, SF-36 physical and HAQ were 0.1, 0.48 and 0.05, respectively. The overall numeric improvement (SRM) in utility was 0.10 (0.37) with EQ-5D and 0.03 (0.27) with SF-6D. Improvement overall was similar after surgery in the upper versus the lower limb, but was larger in patients undergoing replacement surgery than in patients undergoing other surgical procedures (SRM 1.54 vs 1.08 for pain in the actual joint). CONCLUSIONS: Surgical procedures have a major positive impact on pain in the actual joint, but improvement is less in other dimensions of health. Health benefits were larger after replacement surgery than after other surgical procedures.
18085741 Associations of erosive arthritis with anti-cyclic citrullinated peptide antibodies and MH 2008 Jan OBJECTIVE: To determine the associations of erosive arthritis (EA) with anti-cyclic citrullinated peptide (anti-CCP) antibodies and major histocompatibility class (MHC) II alleles in systemic lupus erythematosus (SLE). METHODS: One hundred four patients with SLE were evaluated for arthritis and classified as EA, nonerosive arthritis, or no arthritis. EA was further classified as major or minor erosions. Sera from patients and 130 serum controls were tested for anti-CCP2 and rheumatoid factor (RF). Patients and 117 genetic controls were genotyped for HLA-DRB1 and HLA-DQB1. Statistical associations were tested using chi-square tests and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Eight patients (8%) were anti-CCP+ and they accounted for 11% (8/71) of patients with synovitis. Twelve patients (11%) had EA. Among patients with synovitis, EA was associated with anti-CCP (OR 28.5, 95% CI 4.7-173.8, p = 0.001), with a weaker association for RF (p = 0.3). Six patients with EA had major erosions and also met criteria for rheumatoid arthritis (RA). Four of these patients (67%) were anti-CCP+. HLA-DQB1*0302 was associated with EA (p = 0.01), with similar trends for HLA-DRB1*0401 and 2 copies of the shared epitope (SE). There were trends for associations of HLA-DQB1*0302 and 2 SE copies with anti-CCP production. CONCLUSION: The frequency of EA in SLE is likely to be higher than previously reported. Anti-CCP+ patients with SLE are more likely to have EA. Anti-CCP may be a useful serological marker for EA for patients presenting with synovitis. Anti-citrulline antibodies may have a pathogenic role in the development of major erosions, resulting in clinical features that overlap SLE with RA (rhupus).
18032536 Polymorphisms in the ficolin 1 gene (FCN1) are associated with susceptibility to the devel 2007 Dec OBJECTIVES: We investigated the possible association of rheumatoid arthritis (RA) with single nucleotide polymorphisms (SNP) within the ficolin (FCN) genes. Two SNPs in the FCN1 gene, four SNPs in the FCN2 gene and one SNP in the FCN3 gene were studied. METHODS: The SNPs within the FCN genes were detected by an experimental INNO-LiPA methodology (Innogenetics, Belgium) in a population consisting of 338 RA patients and 595 controls. The significant SNPs were further evaluated in two subpopulations and related to carriage of the human leukocyte antigen-shared epitope (HLA-SE), rheumatoid factor (RF) and the presence of anti-citrullinated protein/peptide antibodies (ACPA). RESULTS: Two SNPs in the FCN1 gene were significantly associated with RA: the A allele rs2989727 was significantly increased in RA patients (67%) compared with controls (60%) (P = 0.002). Also, the frequency of the G allele of rs1071583 was increased in RA patients (68%) compared with controls (61%) (P = 0.003). Analysis of agreement between SNPs suggested strong linkage between rs2989727 and rs1071583. Carriage of a FCN1 SNP was independent of carriage of the HLA-SE, RF status and ACPA positivity. CONCLUSIONS: We describe two linked SNPs in the FCN1 gene that are associated with the development of RA.
18487628 Treatment impact on estimated medical expenditure and job loss likelihood in rheumatoid ar 2008 Jul OBJECTIVES: Quality of life (QoL) improvement is important to demonstrate in RA clinical trials, but can be abstract. More meaningful measures of QoL include medical expenditure and job loss, aspects that have marked importance for RA patients, physicians and society. We re-examined previous positive QoL findings for abatacept over placebo by converting existing QoL measures into estimated medical expenditure and estimated likelihood of job loss. METHODS: Two double-blind, placebo-controlled, multicentre randomized clinical trials were undertaken: one for MTX failure (n = 652) and one for more severe anti-TNF failure patients (n = 391). Based on derived scores using previously published formulae, measures of monthly medical expenditure, current inability to work and job loss at 6 months, 1 yr and 2 yrs were analysed. RESULTS: Abatacept led to greater reduction in medical expenditure over time in MTX failure ($152 lower) and anti-TNF failure patients ($122 lower) compared with placebo at end-point. Likewise, significantly more reduction in likelihood for current and future job loss was achieved with abatacept compared with placebo, which has 25-64% greater likelihood. CONCLUSIONS: QoL changes provided greater reduction in medical expenditure and likelihood of an inability to work. The strong effect sizes obtained for all significant analyses suggest that the results are clinically meaningful. Moreover, given the nature of the variables, results should also be meaningful for patients, physicians, employers and health care insurance entities. Limitations are discussed regarding using estimated outcomes rather than analysis of actual outcomes.
18218664 Ultrasound and Doppler micro-imaging in a model of rheumatoid arthritis in mice. 2008 Dec OBJECTIVES: The evaluation of joints in arthritis using conventional ultrasonography is not really feasible in mice because of the small size of the animal. However, compared with classical analysis (clinical and histological examination) it is a non-invasive method that allows follow-up of the same animal throughout the whole experiment. Moreover, power Doppler allows the study of blood flow that reflects inflammatory activity within the synovium of arthritic joints. Our aim was to determine whether ultrasonography analysis could accurately detect arthritis lesions in a mouse model of rheumatoid arthritis, namely collagen-induced arthritis. METHODS: Collagen-induced arthritis was induced in 28 mice by immunising with collagen type II. Every week for 8 weeks, ultrasonography and Doppler analysis were performed on knees and ankles of all mice using the ultrasound biomicroscope (UBM), which is particularly dedicated to studying the mouse. Clinical and histological evaluations were performed as usual. RESULTS: We established a semiquantitative analysis by setting an UBM scoring. UBM grades were correlated to clinical and histological scores of arthritis. Vascularisation within the synovium could be estimated by power Doppler analysis and a semiquantitative vascularisation scale was established, which allowed us to show a good correlation between vascularisation scores and histological or clinical scores of arthritis. CONCLUSIONS: This is one of the first studies that shows it is possible to visualise a selected set of joints in a small animal using UBM analysis. It provides new perspectives in evaluating experimental models of rheumatoid arthritis and other joint diseases.
16507211 Atypical CD8+ cutaneous T-cell lymphoma after immunomodulatory therapy. 2006 Jan Systemic immunomodulatory agents have recently been approved for the treatment of rheumatoid arthritis and psoriasis. Although lymphomas are known to emerge in the setting of immunosuppressive therapy, it has not been well described or established for the newer biologic immune response modifiers. Herein, we describe 2 patients who developed unusual CD8+ cutaneous lymphoproliferative disorders after treatment with efalizumab and infliximab. The mechanisms and occurrence of lymphoma after immune response modifiers are discussed.
16736519 The ratio of circulating osteoprotegerin to RANKL in early rheumatoid arthritis predicts l 2006 Jun OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that may result in debilitating joint deformities with destruction of bone and cartilage. Inflammation is still considered the pivotal inducer of both components of joint damage. Results of recent animal studies suggested a prominent contribution of osteoclastic bone resorption that could be dissociated from inflammation. RANKL and its natural decoy receptor, osteoprotegerin (OPG), play key roles in osteoclast activation. In a group of patients with early RA not treated with disease-modifying drugs, we tested the hypothesis that osteoclast activation, reflected by the serum OPG:RANKL ratio at baseline, is negatively associated with progression of bone damage, independent of inflammation. METHODS: OPG and RANKL levels, together with a parameter of inflammation (first-year time-averaged erythrocyte sedimentation rate [tESR]), were measured in 92 patients with newly diagnosed early active RA who were participants in a randomized study. The tESR and the OPG:RANKL ratio were evaluated for the ability to predict 5-year radiographic progression of joint damage. RESULTS: The first-year tESR and the OPG:RANKL ratio, as measured at baseline, independently predicted 5-year radiographic progression of joint damage (both P < or = 0.001). Progression of radiographic damage was greatest in patients with a high tESR and a low OPG:RANKL ratio and was lowest in patients with a low tESR and a high OPG:RANKL ratio. CONCLUSION: This study in patients with early untreated RA is the first to confirm the findings in animal models of arthritis, that radiographic progression of the bone component of joint destruction is dependent on both inflammation (tESR) and osteoclast activation (the OPG:RANKL ratio).
18988134 [Rheumatic diseases in pregnancy]. 2008 Nov Rheumatic diseases can influence the reproduction, the course of pregnancy and the development of the fetus. The inflammatory rheumatic disease itself can be modulated in its activity in terms of amelioration or exacerbation of the rheumatic symptoms. The associations between rheumatic diseases and pregnancy will be illustrated with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and systemic lupus erythematosus as examples. Antirheumatic drug therapy during pregnancy and the breast feeding period has to be adapted critically.
18658144 Specific and overlapping sphingosine-1-phosphate receptor functions in human synoviocytes: 2008 Nov Sphingosine-1-phosphate (S1P), via interaction with its G protein-coupled receptors, regulates various physiological and pathological responses. The present study investigated the role of S1P/S1P receptor signaling in several functional responses of human fibroblast-like synoviocytes (FLSs) that may contribute to the pathogenesis of rheumatoid arthritis (RA). We report that FLSs express the S1P(1), S1P(2), and S1P(3) receptors. Moreover, exogenously applied S1P induces FLS 1) migration, 2) secretion of inflammatory cytokines/chemokines, and 3) protection from apoptosis. Using specific S1P receptor agonists/antagonists, we determined that S1P stimulates FLS migration through S1P(1) and S1P(3), induces cytokine/chemokine secretion through S1P(2) and S1P(3), and protects from cell apoptosis via S1P(1). The S1P-mediated cell motility and cytokine/chemokine secretion seem to be regulated by the p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK, and Rho kinase signal transduction pathways. Interestingly, treatment of FLSs with tumor necrosis factor-alpha increases S1P(3) expression and correlates with the enhancement of S1P-induced cytokine/chemokine production. Our data suggest that S1P(1), S1P(2), and S1P(3) play essential roles in the pathogenesis of RA by modulating FLS migration, cytokine/chemokine production, and cell survival. Moreover, the cytokine-rich environment of the inflamed synovium may synergize with S1P signaling to exacerbate the clinical manifestations of this autoimmune disease.
16644493 [Monoclonal antibodies in the treatment of rheumatoid arthritis: toward a therapeutic revo 2006 Apr The progress of immunopathology allowed the development of targeted drugs or biotherapies. Among them, monoclonal antibodies against T or B lymphocytes or against a cytokine are reported. Monoclonal anti-TNF antibodies are a major therapeutic advance because they can stop the clinical, biological and radiographic evolution of rheumatoid arthritis (RA). Monoclonal anti-CD20 lymphocytes give promising results; they are able to induce prolonged remissions. Monoclonal anti-IL6 receptors are currently being evaluated. They are efficacious in adult RA and in Still's disease. Because of the infectious risk linked to these drugs, the ratio benefit/risk must be carefully evaluated before the prescription of a biotherapy.
18777028 [Minimally invasive therapy of rheumatoid cubarthritis]. 2008 Oct With the progression of rheumatoid arthritis more than half of the patients develop an affection of the elbow. Rheumatoid arthritis is the most common cause of elbow arthritis. The complexity of the rheumatic disease, which typically affects many joints, demands an individual therapeutic plan that can only be developed and accomplished successfully, when rheumatologists, rheumatoid surgeons and other specialists cooperate. Consistent use of approved and improved pharmaceuticals is abating the rate of rheumatoid cubarthritis. In cases of recurrent cubarthritis despite adequate medication, adverse reactions and other problems should be borne in mind before making a decision to change to more aggressive medication or synovectomy. Minimally invasive local measures, such as synoviorthesis and arthroscopic synovectomy can relieve pain and swelling, however, if lesions of the cartilage already exist, progressive joint destruction cannot be prevented. In early phases of rheumatoid cubarthritis with tight ligaments and thin synovial lining we prefer synoviothesis. In cases with recurrent cubarthritis after synoviorthesis or strong proliferation of the tunica synovialis, arthroscopic synovectomy is advantageous. Arthroscopic synovectomy is most effective in cases when there is ligament laxity in the sense of a late synovectomy, as removal of loose bodies, smoothening of the cartilage, release of the joint capsule and possibly arthroscopy-assisted resection of the radius head can be performed.
17014003 Declining trend in the incidence of rheumatoid factor-positive rheumatoid arthritis in Fin 2006 Nov OBJECTIVE: To investigate trends in the incidence of rheumatoid arthritis (RA) in Finland. METHODS: We studied all the subjects entitled to receive drug reimbursement for chronic inflammatory joint diseases in 5/21 central hospital districts (population base about 1 million adults) in Finland during 2000. The incidence rates and the mean age at disease onset were compared with those from 1980, 1985, 1990, and 1995. RESULTS: A total of 714 subjects were entitled to drug reimbursement for chronic inflammatory joint disease that had started at the age of 16 or over. Of them, 321 satisfied the American College of Rheumatology classification criteria for RA, 198 had spondyloarthropathy, and 195 had undifferentiated oligo- or polyarthritis. The incidence of RA was 29.1/100,000 (95% CI 26.0-32.5); the figures for rheumatoid factor (RF)-positive RA and RF-negative RA were 18.2 (95% CI 15.8-21.0) and 10.8 (95% CI 9.0-12.9)/100,000, respectively. The incidence of RA was 36.9 (95% CI 32.1-42.2)/100,000 among women and 20.8 (95% CI 17.2-25.1)/100,000 among men. The age- and sex-adjusted incidence rate ratio declined from 1.00 in the referent year 1980 to 0.55 (95% CI 0.46-0.66) in 2000. A declining trend was evident for the incidence of RF-positive RA (p < or = 0.001). CONCLUSION: We verified the declining trend for the incidence of RF-positive RA in both sexes in Finland. Although the etiology of RA remains unknown, public health measures may reduce the risk of RA in the general population.
17190115 A method for pattern recognition. 2006 Winter Although pattern is a dominant concept in nursing science, only Newman's method for recognizing pattern has been fully articulated and widely used in research about the human health experience. This article proposes an alternative, less costly method to facilitate research with larger numbers of participants in clinical settings. Cluster analysis, a quasi-quantitative technique, and content analysis were combined to produce a technique for recognizing patterns of person-environment interaction. Results from two studies with persons experiencing a highly variable chronic illness, rheumatoid arthritis, indicated that this new approach identifies distinct common patterns of person-environment interaction. Sufficient detail about the nature of each pattern resulted to facilitate further knowledge development about the health experience and to provide guidance in structuring nursing care.
17153856 Early environmental exposure and the development of lupus. 2006 Systemic lupus erythematosus (SLE) is a complex trait with evidence of polygenic inheritance influenced by environmental factors. However, the precise underlying causes of SLE remain unclear. A number of environmental exposures have been associated with lupus or related autoimmune phenomena. Evidence suggests that some environmental exposures need to be present many years before the onset of SLE. Both SLE and rheumatoid arthritis (RA) can occur in very young children and this supports the possibility that important environmental factors must be present during or before this time. In addition, the immune pathology, including autoantibody production, in adult lupus may begin years before clinical disease. There is also evidence that the developing immune system demonstrates developmental plasticity and can be permanently altered or 'programmed' by the early environment. We describe how early life environmental influences including infectious exposure may lead to autoantibody production in later life thus beginning the journey that leads to autoimmune diseases such as lupus in susceptible individuals.
18983698 Immune regulation of bone loss by Th17 cells. 2008 A significant macrophage and T-cell infiltrate commonly occurs in inflammatory joint conditions such as rheumatoid arthritis that have significant bone destruction. Cytokines produced by activated macrophages and T cells are implicated in arthritis pathogenesis and are involved in osteoclast-mediated bone resorption. The scope of the present review is to analyze current knowledge and to provide a better understanding of how macrophage-derived factors promote the differentiation of a novel T-helper subset (Th17) that promotes osteoclast formation and activation.
17306038 Cells of the synovium in rheumatoid arthritis. T lymphocytes. 2007 Recent findings have substantiated the importance of T lymphocytes to the pathogenesis of rheumatoid arthritis (RA). Here, we review emerging data regarding genetic predisposition, spontaneous animal models of arthritis, and cell-cell interactions that implicate T cells as driving synovial inflammation and joint destruction. Information regarding the proinflammatory role of interleukin-17-producing T cells and the functional state of regulatory T cells both in animal models and in patients with RA is also discussed. In light of the overwhelming evidence that disrupted T-cell homeostasis greatly contributes to joint pathology in RA, the therapeutic potential of targeting activators of pro-inflammatory T cells or their products is compelling.
17083765 A proposed approach to recognise "near-remission" quantitatively without formal joint coun 2006 Nov A proposed approach is presented to recognise a status of "near-remission" in a patient with rheumatoid arthritis (RA) on the basis of patient self-report questionnaire data without formal joint counts or laboratory tests. Indices of patient-reported outcome (PRO) measures distinguish active from control treatments in RA clinical trials at levels similar to American College of Rheumatology (ACR) or disease activity score (DAS) 28 improvement levels. PRO measures on a multidimensional health assessment questionnaire (MDHAQ) can be compiled into a routine assessment of patient index data (RAPID) score. RAPID 3 includes the three PRO measures from the ACR Core Data Set - physical function, pain, and global estimate. RAPID 4 adds a self-report joint count from a rheumatoid arthritis disease activity index (RADAI). RAPID 5 adds a physician estimate of global status. RAPID cores may be classified into four preliminary proposed categories, as "near-remission" (0-1), "low severity" (1.01-2), "moderate severity" (2.01-4), and "high severity" (> 4), analogous to the four categories of the DAS28 of "remission" (< 2.6), as well as "low" (2.6-3.19), "moderate" (3.2-5.1), and "high" (> 5.1) disease activity. RAPID scores are correlated significantly with DAS28 (rho = 0.64-0.67, p < 0.001), and about 75% of patients with DAS < 2.6 have RAPID scores < 2, while about 75% of patients with DAS > 5.1 have RAPID scores > 4. RAPID data are available on one side of one page, and are feasible to collect in standard clinical care. RAPID 3 scores may be calculated in about 10 seconds, and RAPID 4 and RAPID 5 scores in 20 to 30 seconds. RAPID scores every 3 months or more on simple flowsheets can be a basis for a "continuous quality improvement" strategy in standard clinical care to recognise a need for aggressive therapy, an inadequate response to a therapy, and "near- remission" status.
17499874 Reconditioning in patients with rheumatoid arthritis. 2007 Jul Rheumatologists traditionally have recommended to rheumatoid arthritis (RA) patients that they avoid dynamic and weight-bearing exercises because of concerns about aggravating joint inflammation and accelerating joint damage in such patients. These restrictions may lead to inadequate levels of physical activity and deconditioning. OBJECTIVE: To review the literature on tolerance and benefits of conditioning training, including dynamic and weight-bearing activities in RA patients. MATERIALS AND METHODS: Medline and Cochrane databases were searched with the keywords RA, rehabilitation, physical therapy, exercise, reconditioning, and rest. RESULTS: Rest therapy is more deleterious than beneficial in most patients with RA and may lead to deconditioning. Dynamic and aerobic exercises do not aggravate joint inflammation and do not accelerate joint damage in such patients. The important goal of reconditioning patients with RA is the prevention of functional decline. Conditioning programs designed to prevent widespread morbidities in healthy subjects are attainable by most RA patients, but an individualized approach to exercise is required. CONCLUSION: RA patients need to be persuaded about the effectiveness and safety of moderate and even high-intensity exercise.
17469103 Association of anti-cyclic citrullinated peptide antibody levels with PADI4 haplotypes in 2007 May OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are rheumatoid arthritis (RA)-specific serologic markers. RA susceptibility has been associated with HLA-DRB1 shared epitope (SE) alleles and single-nucleotide polymorphism (SNP) haplotypes in the peptidyl arginine deiminase 4 gene (PADI4). This study was undertaken to determine whether anti-CCP levels are associated with PADI4 haplotypes and/or SE alleles in Korean patients with RA. METHODS: Three nonsynonymous SNPs in PADI4 (padi4_89, padi4_90, and padi4_92) and SE alleles were genotyped, and serum anti-CCP levels were measured, in 311 patients with nonerosive or erosive RA. The relationships between anti-CCP levels and PADI4 haplotypes and/or SE alleles were analyzed statistically. RESULTS: Anti-CCP levels were significantly higher in patients carrying the PADI4 RA risk haplotype than in patients who did not have the risk haplotype, among anti-CCP-positive patients with RA with a disease duration of or=141 months (P = 0.0037) and among those who had erosive RA (P = 0.000098), but not among patients who had a shorter disease duration or those who had nonerosive RA. CONCLUSION: The PADI4 RA risk haplotype is associated with increased anti-CCP levels in RA patients with disease of short duration, and PADI4 may play a role in early RA. In contrast, SE alleles are associated with increased anti-CCP levels in RA patients with very longstanding disease and in patients with erosive RA, suggesting that SE alleles play a role in very late RA.
18821073 NK and NKT cell dynamics after rituximab therapy for systemic lupus erythematosus and rheu 2009 Feb Biomarkers of clinical response to rituximab (RTX) therapy and early predictors of outcome are still under investigation. We report a flow cytometric immunophenotyping analysis from peripheral blood leukocyte subpopulations of two patients with systemic lupus erythematosus (SLE) associated thrombocytopenia and one patient with rheumatoid arthritis (RA), before and after 6 weeks of treatment with RTX. Our results show a reduced population of CD19(+) expressing cells (B cells) after RTX treatment in all three patients. Increased frequency of peripheral regulatory CD4(+)CD25(high) T cell subset and the CD3(-)CD16(-)CD56(bright) NK cell subset after RTX therapy were also observed in all patients, the latter being more pronounced in the SLE patient with sustained clinical response. In addition, an increased population of NKT cell subsets was observed in the patients with clinical response. This is the first evaluation of NK and NKT cells as biomarkers of clinical response after rituximab therapy in rheumatic diseases.