Browse

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

ID PMID Title PublicationDate abstract
18761748 Elevated autoantibody content in rheumatoid arthritis synovia with lymphoid aggregates and 2008 INTRODUCTION: The purpose of this study was to quantitatively evaluate the contribution of synovial lymphoid aggregates to autoantibody (rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP]) and total immunoglobulin (IgG and IgM) production in rheumatoid arthritis (RA) patients and the effect thereon of the B-cell-depleting antibody, rituximab, in the ARISE (Assessment of Rituximab's Immunomodulatory Synovial Effects) trial. METHODS: Autoantibodies as well as total IgM and IgG were quantified by enzyme-linked immunosorbent assay in extracts of synovial tissues and matched serum from patients with RA or osteoarthritis (OA). Synovial biopsies and serum were obtained at baseline and 8 weeks following rituximab therapy in 14 RA patients. A synovial/serum index (SSI) was calculated as the ratio of synovial to serum antibody/albumin, with values above 1 representing synovial enrichment. Lymphoid aggregates were evaluated histologically. RESULTS: Anti-CCP IgG, but not RF-IgM, was significantly enriched in RA synovia compared with serum. Total IgM and IgG were also enriched in RA, but not in OA. SSI correlated significantly with mRNA content for both IgM and IgG, demonstrating that it reflected synovial immunoglobulin production. RA synovia with lymphocyte aggregates contained significantly elevated RF-IgM and anti-CCP IgG compared with tissues with diffuse lymphoid infiltration. Rituximab treatment did not affect synovial autoantibody or total immunoglobulin SSI overall. However, in aggregate-containing tissues, rituximab significantly reduced total IgM and IgG SSI as well as IgM and IgG1 mRNA. Surprisingly, RF-IgM and anti-CCP IgG SSIs were unchanged by rituximab in aggregate-containing synovia. CONCLUSIONS: Combined with earlier observations that synovial lymphoid aggregates are unaltered by rituximab treatment, these data suggest that lymphoid aggregates may provide a protective niche for autoantibody-producing cells.
18587627 Comparison among total knee arthroplasties with a mobile bearing: menisci versus rotating 2008 Sep A retrospective study was conducted on 60 patients (53 females, seven males with a mean age of 68 years and 5 months) who underwent a total knee replacement using a mobile bearing. The diagnosis was primary osteoarthritis in 57 cases and rheumatoid arthritis in three cases. None of the patients underwent a bilateral procedure, thus 60 implants (33 all cementless, three all cemented, 24 with only the tibial component cemented) were considered. Three different groups were identified: Group 1: first 20 total knee arthroplasties with menisci. Group 2: first 20 total knee arthroplasties with rotating platform. Group 3: first 20 total knee arthroplasties with AP glide platform. Clinical and radiological results at the final follow up, although different in time among the three groups, have shown no revision due to mechanical or septic reasons, and no signs of impending failure.
18336287 Expression, regulation and function of asporin, a susceptibility gene in common bone and j 2008 Asporin is an extracellular matrix protein that belongs to the small leucine-rich repeat proteoglycan (SLRP) family of proteins. It is unique among SLRPs in that it lacks a glycosaminoglycan attachment site and contains an asparatic acid (D) repeat at its amino terminus. Its biological role has been unclear, but recent genetic studies have demonstrated association between asporin and various bone and joint diseases, including osteoarthritis, rheumatoid arthritis and lumbar disc disease. Each of these common diseases presents a substantial medical, social and economical burden to societies worldwide. This paper reviews recent progress in the study of asporin, focusing on its expression, regulation and function as well as its role in the molecular pathogenesis of common bone and joint diseases. Asporin is found primarily in regions surrounding skeletal tissue and is up-regulated in disease states. It binds to various growth factors, including TGF-beta and BMP-2, and negatively regulates their activity. By inhibiting binding of TGF-beta1 to its type II receptor, asporin forms a functional feedback loop with TGF-beta1 and regulates its chondrogenic potential. As an extracellular, tissue-specific protein, asporin represents a promising target for phamacogenomic approaches to common bone and joint diseases.
17551378 Control of periodontal infection reduces the severity of active rheumatoid arthritis. 2007 Jun OBJECTIVE: To determine if eliminating periodontal infection and gingival inflammation affects the severity of active rheumatoid arthritis (RA) in patients with chronic inflammatory periodontal disease. METHODS: Twenty-nine subjects with confirmed diagnosis of RA and mild-to-moderate chronic periodontitis of at least 3 years' duration were enrolled in the study. The activity of RA was assessed using the disease activity score test (DAS28). Seventeen subjects completing the study received periodontal treatment consisting of scaling/root planing and oral hygiene instruction; 12 subjects completing the study received no treatment. Participants continued their usual disease-modifying medications for RA without any changes in DMARD therapy during the study period. RA measurements, and periodontal indices were recorded at baseline and at 8 weeks for each participant. Mann-Whitney U and chi tests were used to test for significant differences in the severity of RA in the periodontally treated group compared with the untreated groups. RESULTS: Ten of 17 subjects (58.8%) in the treated group and 2 of 12 subjects (16.7%) in the untreated group showed improvement in RA scores. There was a statistically significant difference in DAS28 (4.3 +/- 1.6 vs. 5.1 +/- 1.2) and erythrocyte sedimentation rate (31.4 +/- 24.3 vs. 42.7 +/- 22) between the treatment and the control groups. CONCLUSION: Control of periodontal infection and gingival inflammation by scaling/root planing and plaque control in subjects with periodontal disease may reduce the severity of RA. This notion is supported by reported subjective improvement in treated patients.
16960930 Comparison of tacrolimus and mizoribine in a randomized, double-blind controlled study in 2006 Nov OBJECTIVE: To compare the efficacy and safety of tacrolimus and mizoribine in patients with rheumatoid arthritis (RA). METHODS: Adult patients with RA with an insufficient response to at least one disease modifying antirheumatic drug (DMARD) were randomized to receive 28 weeks of double-blind treatment with tacrolimus 3 mg once daily or mizoribine 50 mg three times daily. The primary efficacy endpoint was the American College of Rheumatology 20% (ACR20) response. Safety was evaluated by adverse events. RESULTS: A total of 204 patients were enrolled for study (103 in the tacrolimus group, 101 in the mizoribine group). Significantly more patients receiving tacrolimus achieved an ACR20 response compared with mizoribine (48.5 vs 10.0%, respectively; p = 0.001). Tacrolimus was also superior to mizoribine in ACR50 and ACR70 response rate, tender and painful joint counts, swollen joint counts and patient and physician assessments of pain, disease activity, and patient's physical function assessment based on the Modified Health Assessment Questionnaire (p < 0.001). Adverse events were more frequent in the tacrolimus group than the mizoribine group (65.0 vs 59.4%); however, there were no statistically significant differences between treatment groups. CONCLUSION: Tacrolimus improves RA symptoms to a significantly greater extent than mizoribine in patients with RA inadequately controlled with at least one prior DMARD. Tacrolimus has the potential to be a useful and highly effective treatment for RA.
18050189 Treatment of early rheumatoid arthritis: a randomized magnetic resonance imaging study com 2007 Dec OBJECTIVE: To compare the effects of methotrexate (MTX), alone or in combination with intravenous (IV) methylprednisolone (MP) or infliximab, on magnetic resonance imaging (MRI)-detected synovitis, bone edema, and erosive changes in patients with early rheumatoid arthritis (RA). METHODS: Forty-four patients with early RA were randomized to receive MTX alone (MTX group), MTX plus IV MP (IV MP group), or MTX plus infliximab (infliximab group), infused on day 0 and weeks 2, 6, 14, 22, 30, 38, and 46. Gadolinium-enhanced MRI scans of the metacarpophalangeal joints, wrists, and metatarsophalangeal joints were performed at baseline, week 18, and week 52. RESULTS: Scores for MRI-detected synovitis and bone edema improved over time in the 3 groups, with significantly lower synovitis scores in the infliximab group compared with the MTX group and significantly lower bone edema scores in the infliximab group compared with the MTX and the IV MP groups. Scores for MRI-detected erosion significantly increased over time in all groups. There were no differences in erosion scores between the MTX group and the other groups. It is of note that patients treated with IV MP showed more significant progression in MRI-detected erosions compared with patients treated with infliximab. At week 22, response rates according to the American College of Rheumatology 20% improvement criteria (ACR20), the ACR50, and the ACR70 were significantly higher in both the IV MP group and the infliximab group compared with the MTX group. At week 52, remission was achieved in 40% of patients in the MTX group and in 70% of patients in the IV MP and infliximab groups. Health Assessment Questionnaire scores improved significantly over time in all groups, with patients receiving IV MP experiencing significantly more improvement compared with patients treated with MTX alone. No severe side effects were observed, except 1 case of MTX-related pneumonitis. CONCLUSION: The combination of MTX and infliximab is superior to MTX alone for reducing MRI-detected signs of synovitis and bone edema in patients with early RA. Progression of MRI-detected erosion was greater in patients treated with MTX plus IV MP compared with that in patients who received MTX plus infliximab.
18848883 B-cell tolerance checkpoints in health and autoimmunity. 2008 Dec The enormous diversity of the antibody repertoire is generated by two mechanisms: recombination of immunoglobulin (Ig) gene variable (V), diversity (D), and joining (J) gene segments during the early stages of B-cell development in the bone marrow and somatic hypermutation (SHM) of functional Ig genes from antigen-activated B cells within secondary lymphoid organs. Diversity by V(D)J recombination and SHM not only provides protective humoral immunity but also generates potentially harmful clones expressing autoantibodies. Under normal circumstances, several mechanisms regulate the removal of autoreactive B cells and defects in central and peripheral B cell tolerance checkpoints are associated with the development of autoimmunity in humans.
18923976 Multivariate relationships between pain intensity and other aspects of health in rheumatoi 2008 OBJECTIVES: This study analyses the relationships between pain intensity and other aspects of health commonly used to assess disease activity and disability in early rheumatoid arthritis and examines whether such relationships were different between women and men. SUBJECTS AND METHODS: This study included the 189 patients (69% women) with early RA (symptoms <12 months at diagnosis) still remaining in the Swedish TIRA cohort 5 years after inclusion. Disease activity and disability was assessed 3, 6, 12, 18, 24, 36, 48, and 60 months (M0-M60) after inclusion by erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), number of swollen and tender joints, physicians global assessment of disease activity (PGA), grip force average over 10 seconds (Grippit), Grip Ability Test (GAT), Signals of Functional Impairment (SOFI) in hand, lower limb and upper limb, Health Assessment Questionnaire (HAQ), and pain intensity measured with a visual analogue scale (VAS). The variables were divided into meaningful blocks according to the correlation structure in a principal component analysis (PCA) at M60. Using hierarchical partial least squares (PLS) analyses, this study investigated the blocks cross-sectionally to test for correlations with pain intensity at M0 and M60. The blocks at M0 were also used as predictors of pain intensity at M60 in a hierarchical PLS. RESULTS: The strongest relationship was found between pain intensity and the second block, consisting of HAQ and SOFI-lower limb at the cross-sectional analyses in both women and men. The block representing disease activity (i.e., ESR, CRP, PGA, and swollen and tender joints) had the weakest relation to pain intensity. According to the longitudinal analyses, the disease activity variables (block 1) at M0 had the strongest relationship to pain intensity at M60 in men. In contrast, HAQ and SOFI-lower limb (block 2) at M0 had a strong relation to pain intensity in women.
17502360 Cellular targets of interleukin-18 in rheumatoid arthritis. 2007 Nov Recent data are presented which indicate a critical role for interleukin (IL)-18 in rheumatoid arthritis (RA). The T cells and macrophages invading the synovium or in the synovial fluid are the chief cellular targets of IL-18 in RA. Neutrophils, dendritic cells and endothelial cells may also be cellular mediators of IL-18. The direct effect of IL-18 on fibroblast-like synoviocytes or chondrocytes may not be essential or important. In RA, IL-18, which is mainly produced by macrophages, activates T cells and macrophages to produce proinflammatory cytokines, chemokines, adhesion molecules and RANKL which, in turn, perpetuate chronic inflammation and induce bone and cartilage destruction.
18051699 Differential expression of rheumatoid factor-associated cross-reactive idiotypes in Irania 2007 Jan INTRODUCTION: High levels of rheumatoid factors (RF) are detectable in serum of the majority of patients with rheumatoid arthritis (RA), but 5-10% of patients remain seronegative (SN). Despite clinical and genetic similarities between these two subsets of RA, it has been proposed that they may be regarded as distinct clinical entities. METHODS: In the present study a panel of monoclonal antibodies (mAb) recognizing RF-associated cross-reactive idiotypes (CRI) linked to the VH1 (G8), VH4 (LC1), VK3b (17-109) and a mAb recognizing the VK3 subgroup (C7) of immunoglobulin variable region (IgV) gene products were used to quantitate the level of expression of these gene products in serum and synovial fluid of 35 seropositive (SP) and 8 SN RA patients by capture ELISA. RESULTS: While the concentration and relative proportion of the IgV are recognized by the mAb G8, 17-109 and C7 were significantly higher in serum and synovial fluid of the SP RA, compared to the SN-RA patients (G8, p = 0.009; 17-109, p = 0.0001; C7, p = 0.001). The CRI recognized by the mAb LC1 was highly represented in serum and synovial fluid of the SN-RA patients. There have been no significant differences in the level of expression of these IgV gene products (other than the product recognized by C7 mAb in SP patients) between serum and synovial fluid of either group of patients. CONCLUSION: Our results suggest that the expressed repertoire of Ig VH and VK genes in these two subsets of RA is differentially regulated and may be influenced by selective mechanisms leading to positive or negative selection of certain genes.
17043867 The complex role of Fcgamma receptors in the pathology of arthritis. 2006 Dec Autoantibodies of the IgG class and the immune complexes they form are central players in the pathology of rheumatoid arthritis (RA). Receptors for the Fc part of IgG, FcgammaR constitute one of the main effector mechanisms through which IgG immune complexes exert their action. The different members of the FcgammaR family exhibit extensive structural homology leading to redundancy in ligand specificity and signal transduction. Moreover, the initiation of effector mechanisms by IgG immune complexes can also be mediated by the complement system. This strong redundancy and high degree of complexity hampers a direct in vivo analysis of antibody effector pathways. Over the last decade, mice deficient for different combinations of FcgammaR have been generated by gene targeting. These knockout mice provide excellent tools to define the specific contribution of the different FcgammaR to IgG effector pathways in well-established in vivo mouse models for arthritis. This review will discuss the results of the studies that analyze the role of the different members of the FcgammaR family in murine arthritis models and their implications for our understanding of the human disease.
18311833 Leishmanial lipid suppresses tumor necrosis factor alpha, interleukin-1beta, and nitric ox 2008 Mar OBJECTIVE: Leishmanial lipid is a strong immunosuppressor of host cells. Inhibition of the inflammatory responses of synovial cells through induction of apoptosis is one of the main targets of therapeutic intervention in rheumatoid arthritis (RA). This study was undertaken to examine the antiinflammatory and apoptosis-inducing effects of leishmanial lipid on adherent synovial fluid mononuclear cells (SFMCs) in patients with RA. METHODS: Lipid was extracted from a Leishmania donovani promastigote (MHO/IN/1978/UR6) by the Bligh and Dyer method. Nitric oxide (NO) was measured using the Griess reaction, and enzyme-linked immunosorbent assays for cytokines, NF-kappaB, and cytochrome c were performed. Levels of cytokines, inducible nitric oxide synthase, caspases, Bcl-2, Bax, t-Bid, and cytochrome c in the cell lysate and of NF-kappaB p65 in the nucleus were determined by Western blotting. Microscopic analysis, nuclear staining, DNA fragmentation assay, fluorescence-activated cell sorting, colorimetric assay for caspases, and fluorescent probe for measurement of mitochondrial membrane potential were used to study the leishmanial lipid-induced apoptotic pathway in SFMCs. RESULTS: Leishmanial lipid inhibited the release of tumor necrosis factor alpha, interleukin-1beta, and NO in the culture, decreased their cytosolic protein levels, and decreased NF-kappaB p65 levels in SFMCs, in a dose-dependent manner. It had the reverse effect on interleukin-10 levels. Leishmanial lipid-induced apoptosis involved the activation of caspase 3, caspase 9, and Bax, the release of cytochrome c, the alteration of mitochondrial membrane potential, and the down-regulation of Bcl-2. CONCLUSION: These results suggest that leishmanial lipid has strong antiinflammatory and apoptosis-inducing effects on SFMCs from patients with RA, and that apoptosis occurs via the mitochondrial pathway.
18287210 MF498 [N-{[4-(5,9-Diethoxy-6-oxo-6,8-dihydro-7H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylbenzy 2008 May Previous evidence has implicated E prostanoid receptor 4 (EP4) in mechanical hyperalgesia induced by subplantar inflammation. However, its role in chronic arthritis remains to be further defined because previous attempts have generated two conflicting lines of evidence, with one showing a marked reduction of arthritis induced by a collagen antibody in mice lacking EP4, but not EP1-EP3, and the other showing no impact of EP4 antagonism on arthritis induced by collagen. Here, we assessed the effect of a novel and selective EP4 antagonist MF498 [N-{[4-(5,9-diethoxy-6-oxo-6,8-dihydro-7H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylbenzyl]sulfonyl}-2-(2-methoxyphenyl)acetamide] on inflammation in adjuvant-induced arthritis (AIA), a rat model for rheumatoid arthritis (RA), and joint pain in a guinea pig model of iodoacetate-induced osteoarthritis (OA). In the AIA model, MF498, but not the antagonist for EP1, MF266-1 [1-(5-{3-[2-(benzyloxy)-5-chlorophenyl]-2-thienyl}pyridin-3-yl)-2,2,2-trifluoroethane-1,1-diol] or EP3 MF266-3 [(2E)-N-[(5-bromo-2-methoxyphenyl)sulfonyl]-3-[5-chloro-2-(2-naphthylmethyl)phenyl]acrylamide], inhibited inflammation, with a similar efficacy as a selective cyclooxygenase 2 (COX-2) inhibitor MF-tricyclic. In addition, MF498 was as effective as an nonsteroidal anti-inflammatory drug, diclofenac, or a selective microsomal prostaglandin E synthase-1 inhibitor, MF63 [2-(6-chloro-1H-phenanthro[9,10-d]imidazol-2-yl)isophthalonitrile], in relieving OA-like pain in guinea pigs. When tested in rat models of gastrointestinal toxicity, the EP4 antagonist was well tolerated, causing no mucosal leakage or erosions. Lastly, we evaluated the renal effect of MF498 in a furosemide-induced diuresis model and demonstrated that the compound displayed a similar renal effect as MF-tricyclic [3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone], reducing furosemide-induced natriuresis by approximately 50%. These results not only suggest that EP4 is the major EP receptor in both RA and OA but also provide a proof of principle to the concept that antagonism of EP4 may be useful for treatment of arthritis.
17696462 An inflammatory arthritis-associated metabolite biomarker pattern revealed by 1H NMR spect 2007 Sep Rheumatoid arthritis, a debilitating, systemic inflammatory joint disease, is likely accompanied by alterations in circulating metabolites. Here, an 1H NMR spectroscopy-based metabolomics approach was developed to establish a metabolic 'biomarker pattern' in a model of rheumatoid arthritis, the K/BxN transgenic mouse. Sera obtained from arthritic K/BxN mice (N = 15) and a control population (N = 19) having the same genetic background, but lacking the arthritogenic T-cell receptor KRN transgene, were compared by 1H NMR spectroscopy. A unique method was developed by combining technologies such as ultrafiltration to remove proteins from serum samples, quantitative 'targeted profiling' of known metabolites, pseudo-quantitative profiling of unknown resonances, a supervised O-PLS-DA pattern recognition analysis, and a metabolic-pathway based network analysis for interpretation of results. In total, 88 spectral features were profiled (59 metabolites and 28 unknown resonances). A highly significant subset of 18 spectral features (15 known compounds and 3 unknown resonances) was identified (p = 0.00075 using MANOVA) that we term a 'metabolic bioprofile'. We identified metabolites relating to nucleic acid, amino acid, and fatty acid metabolism, as well as lipolysis, reactive oxygen species generation, and methylation. Pathway analysis suggested a shift from metabolites involved in numerous reactions (hub-metabolites) toward intermediates and metabolic endpoints associated with arthritis. The results attest to the metabolic complexity of systemic inflammation and to the power of the experimental approach for identifying a wide variety of disease-associated marker candidates. The diagnostic and prognostic implications of monitoring a spectrum of metabolic events simultaneously using serum samples is discussed with respect to the potential for individualized medicine.
18625443 Is the generation of neo-antigenic determinants by free radicals central to the developmen 2008 Jul Biomolecules are susceptible to many different post-translational modifications that have important effects on their function and stability, including glycosylation, glycation, phosphorylation and oxidation chemistries. Specific conversion of aspartic acid to its isoaspartyl derivative or arginine to citrulline leads to autoantibody production in models of rheumatoid disease, and ensuing autoantibodies cross-react with native antigens. Autoimmune conditions associate with increased activation of immune effector cells and production of free radical species via NADPH oxidases and nitric oxide synthases. Generation of neo-antigenic determinants by reactive oxygen and nitrogen species ROS and RNS) may contribute to epitope spreading in autoimmunity. The oxidation of amino acids by peroxynitrite, hypochlorous acid and other reactive oxygen species (ROS) increases the antigenicity of DNA, LDL and IgG, generating ligands for which autoantibodies show higher avidity. This review focuses on the evidence for ROS and RNS in promoting the autoimmune responses observed in diseases rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It considers the evidence for ROS/RNS-induced antigenicity arising as a consequence of failure to remove or repair ROS/RNS damaged biomolecules and suggests that an associated defect, probably in T cell signal processing or/or antigen presentation, is required for the development of disease.
17435838 [Prevalence of anti-CCP antibodies in systemic sclerosis]. 2007 Jan Joint involvement in systemic sclerosis (SSc) commonly occurs as arthralgias, while a true arthritis is less frequent. The most common arthritis developing in SSc is rheumatoid arthritis (RA) and its diagnosis may be misled by concomitant joint contracture or tendon sheath involvement due to SSc. Anti-citrullinated cyclic peptide (CCP) antibodies are an emerging tool to diagnose RA and have shown to be more specific than rheumatoid factor. We assessed the prevalence of anti-CCP antibodies in SSc patients and evaluated their sensitivity and specificity for associated RA. Searching for RF and anti-CCP antibodies and joint examination were carried out in sixty consecutive SSc patients. Hands and feet standard x-rays were performed in patients complaining with arthralgia and/or arthritis. Six out of sixty (10%) SSc patients had RA according to 1987 ARA revised criteria. Anti-CCP were detected in 5 patients (sensitivity 83%) and RF was present in all RA patients (sensitivity 100%). However, anti-CCP antibodies had a much higher specificity (94%) than RF (41%) for RA. Our study suggests that anti-CCP antibodies are a useful test to identify patients with SSc having also RA. This is crucial in the management of SSc because may allow an adequate therapy of RA and prevent further joint damage in patients who already have a poor quality of life.
18619867 Variation in the position of the elbow flexion axis after total joint replacement with thr 2008 Sep The instantaneous flexion axes in rheumatoid patients treated with a Kudo (Biomet UK Ltd, Swindon, UK), Capitellocondylar (Johnson & Johnson Orthopaedics Inc, Raynham, MA), or GSB III (Zimmer GmbH, Winterthur, Switzerland) elbow prosthesis were calculated using radiostereometric analysis and compared with those previously found in the normal elbow in vivo. Variability in the flexion axis position was greater in the prosthetic elbows than reported for healthy subjects. This was especially evident for the unlinked Kudo prosthesis, with dispersions of the axes up to 84.3 degrees in the frontal and 45.0 degrees in the horizontal plane. Corresponding values for the unlinked Capitellocondylar prosthesis were 19.7 degrees and 20.9 degrees. The linked GSB III prosthesis was the most constrained, with dispersions within 15.4 degrees in the frontal and 4.6 degrees in the horizontal plane. The unlinked elbow prostheses displayed considerable axis dispersion under physiologic conditions. Implant design seems to be able to compensate for this to some extent, as indicated, for example, by the results of the Capitellocondylar prosthesis.
17548411 Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheum 2007 Jun 5 BACKGROUND: Rheumatoid factor (RF) and autoantibodies against cyclic citrullinated peptide (CCP) are markers that might help physicians diagnose rheumatoid arthritis. PURPOSE: To determine whether anti-CCP antibody more accurately identifies patients with rheumatoid arthritis and better predicts radiographic progression than does RF. DATA SOURCES: MEDLINE through September 2006 and reference lists of retrieved studies and review articles. STUDY SELECTION: Studies in any language that enrolled at least 10 participants and that examined the role of anti-CCP antibody and RF in the diagnosis or prognosis of known or suspected rheumatoid arthritis. DATA EXTRACTION: Two authors independently evaluated studies for inclusion, rated methodological quality, and abstracted relevant data. DATA SYNTHESIS: The DerSimonian-Laird random-effects method was used to summarize sensitivities, specificities, and positive and negative likelihood ratios from 37 studies of anti-CCP antibody and 50 studies of RF. The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-CCP antibody were 67% (95% CI, 62% to 72%), 95% (CI, 94% to 97%), 12.46 (CI, 9.72 to 15.98), and 0.36 (CI, 0.31 to 0.42), respectively. For IgM RF, the values were 69% (CI, 65% to 73%), 85% (CI, 82% to 88%), 4.86 (CI, 3.95 to 5.97), and 0.38 (CI, 0.33 to 0.44). Likelihood ratios among IgM RF, IgG RF, and IgA RF seemed to be similar. Results from studies of patients with early rheumatoid arthritis were similar to those from all studies. Three of 4 studies found that risk for radiographic progression was greater with anti-CCP antibody positivity than with IgM RF positivity. LIMITATIONS: Many studies had methodological limitations. Studies of RF were heterogeneous and had wide ranges of sensitivity and specificity. CONCLUSIONS: Anti-CCP antibodies are more specific than RF for diagnosing rheumatoid arthritis and may better predict erosivedisease.
16903811 Spondyloarthropathy: an independent risk factor for kidney stones. 2006 Aug PURPOSE: To better stratify risk and to verify previous prevalence reports, we conducted a retrospective cohort study comparing the lifetime incidence of nephrolithiasis in patients with spondyloarthropathies (SpA) and rheumatoid arthritis (RA). PATIENTS AND METHODS: Patients with SpA or rheumatoid factor-positive RA were identified from the rheumatology clinics of two Veterans Affairs hospitals and the University of Minnesota. Among them, 168 were confirmed to meet the American College of Rheumatology criteria and gave informed consent to participation. They were sent a survey regarding their rheumatologic diagnosis, coexistent conditions, medications, and history of kidney stones. Of the total, 143 patients responded and met the criteria for analysis. Rheumatoid arthritis patients were age and sex matched with SpA patients as controls. RESULTS: Populations were similar in all categories except that RA patients were more likely to have used prednisone (P < 0.001), bisphosphonates (P < 0.001), and calcium supplementation (P = 0.03). Kidney stones were reported by 23 (29.11%) of the 79 SpA patients compared with 8 (12.5%) of the 64 RA patients (chi (2) = 5.75; P = 0.025). Subgroup analysis of self-reporting stone history in 85 patients was found to be reliable on imaging review (sensitivity 82%; specificity 100%). CONCLUSIONS: Self-reporting of kidney stones by patients is a reliable measure. Despite adjusting for medication use and matching two similar arthritic populations, patients with SpA had a higher incidence of kidney stones than those with RA. This finding suggests that SpA is an independent risk factor for nephrolithiasis. Future studies will evaluate urinary risk factors and polymorphisms in the ANKH gene that may predispose to stone formation in this high-risk group.
17852967 Validity and reliability of the instrument Performance and Satisfaction in Activities of D 2008 Mar AIM: This study set out to evaluate the validity and reliability of the instrument Performance and Satisfaction of Activities of Daily Living (PS-ADL) in patients with rheumatoid arthritis (RA). The PS-ADL is a questionnaire including 39 actions divided into 12 activities measuring the degree of difficulty and satisfaction with activity performance. METHOD: Construct validity was examined by factor analysis. For convergent and discriminant validity evaluation, the Performance and the Satisfaction scales were correlated to the Health Assessment Questionnaire (HAQ), the Rheumatoid Arthritis Self-Conception (RASC), pain, fatigue, and mobility. Internal consistency was tested and repeated measurements were taken to establish the Percentage Agreement (PA) and correlation coefficients for test-retest reliability. RESULTS: The factor analysis revealed the PS-ADL scale to be unidimensional. Significant correlations were seen between the Performance and Satisfaction scales and the HAQ (r(s) 0.78, 0.67), and between the RASC and Satisfaction scale (r(s) 0.45). Cronbach's alpha level ranged from 0.41 to 0.92 for the Performance scale and 0.66 to 0.94 for the Satisfaction scale. The percentage agreement (PA) at action level ranged from 68% to 91% for the Performance scale and from 59% to 91% for the Satisfaction scale. CONCLUSION: The PS-ADL is a valid instrument with satisfactory reliability. It is easy to handle and can be recommended for use in RA patients.