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ID PMID Title PublicationDate abstract
24669889 Advantages of a combined rheumatoid arthritis magnetic resonance imaging score (RAMRIS) fo 2014 Mar 26 BACKGROUND: To evaluate a combined rheumatoid arthritis magnetic resonance imaging score (RAMRIS) for hand and foot (HaF-score) in rheumatoid arthritis (RA). METHODS: Magnetic resonance imaging (MRI, 0.2 Tesla) of the dominant hand and foot of 26 ACPA positive RA patients before and 6 months after initiation of methotrexate was obtained. RAMRIS of the hand was complemented by corresponding scoring of the foot (MTP I-V; HaF-score). Disease Activity Score 28 (DAS28) and a tender and swollen joint count (JC) of the joints scored in MRI were recorded. Changes in these scores (Δ) were assessed. RESULTS: ΔHaF-score correlated significantly with ΔDAS28 (r = 0.820, 95%-CI 0.633-0.916). Correlations to ΔDAS28 were best for changes in the synovitis subscore (0.648) and bone marrow edema (0.703). Correlations to ΔDAS28 were significantly better for of the ΔHaF-score than ΔRAMRIS (0.499, 0.139-0.743, p = 0.0368).All patients with at least moderate response (EULAR criteria, n = 11) had continuing disease activity on MRI, including five cases with new erosions, three of them at the feet. Improvements of the hand JC or foot JC were seen in 16 and 15 cases, respectively. However, MRI of the hand or feet improved in only 10 and 9 cases, respectively. No patient fulfilled SDAI remission criteria. CONCLUSIONS: The HaF-score identifies patients with continuing disease activity despite clinical response that would have been missed by consideration of the traditional RAMRIS or the DAS28 alone. Response as opposed to remission may be an insufficient goal in RA as all patients showed continuing disease activity, especially at the feet.
24252844 The peroxisome proliferator activated receptor-γ pioglitazone improves vascular function 2013 Nov 19 BACKGROUND: Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor-γ (PPAR-γ) pioglitazone could promote potent vasculoprotective and anti-inflammatory effects in RA. METHODS AND RESULTS: One hundred forty-three non-diabetic adult RA patients (76.2% female, age 55.2 ± 12.1 [mean ± SD]) on stable RA standard of care treatment were enrolled in a randomized, double-blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3-month duration/arm and a 2-month washout period. Pulse wave velocity of the aorta (PWV), brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), microvascular endothelial function (reactive hyperemia index [RHI]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28-Joint Count Disease Activity Score (DAS-28) C-reactive protein (CRP) and the Short Form (36) Health Survey quality of life questionnaire. When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) (P=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (P=0.02) and CRP levels (P=0.001), while improving lipid profiles. The drug was well tolerated. CONCLUSIONS: Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. CLINICAL TRIAL REGISTRATION URL: ClinicalTrials.gov Unique Identifier: NCT00554853.
24936586 SPP1 rs9138 variant contributes to the severity of radiological damage in anti-citrullinat 2014 Oct OBJECTIVE: We recently reported an association of the SPP1 rs9138 and rs11439060 functional variants with the risk of rheumatoid arthritis (RA), the association being greater in anti-citrullinated protein autoantibody (ACPA)-negative patients. We hypothesised that SPP1 may contribute to the severity of joint destruction in RA, specifically in the ACPA-negative population. METHODS: Patients with RA in the ESPOIR cohort underwent genotyping for SPP1 rs9138 and rs11439060. Radiographs of the hands and feet were obtained at the first visit and at 1- and 2-year follow-up. Association analyses were performed by ACPA status. A replication study of the relevant subset of the Leiden Early Arthritis Clinic (EAC) cohort was performed. RESULTS: In the ESPOIR cohort (652 patients), rs9138 was significantly associated with radiological progression of joint destruction at 2 years, the association being restricted to 358 ACPA-negative patients (p=0.034). In the replication study with the Leiden EAC cohort (273 ACPA-negative patients), rs4754, which is in complete linkage disequilibrium with rs9138, was significantly associated with joint damage progression in ACPA-negative patients at 2- and 7-year follow-up (p=0.019 and p=0.005, respectively). Combined analysis of the two cohorts revealed a 0.95-fold rate of joint destruction per year per minor allele (p=0.022). CONCLUSIONS: The SPP1 rs9138 variant contributes to joint damage progression in ACPA-negative RA.
23936360 Tocilizumab induced acquired factor XIII deficiency in patients with rheumatoid arthritis. 2013 Factor XIII is one of the twelve coagulation factors and also known as a fibrin-stabilizing factor. In 2012, we encountered a male RA patient with hemorrhagic factor XIII deficiency who had been treated with tocilizumab for two years. There are few reports regarding the relationship between tocilizumab (a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)) and factor XIII. We measured the factor XIII activity levels in the plasma of 40 RA patients (10 patients treated without biologics, 30 patients treated with biologics (15 patients treated with necrosis factor inhibitors and 15 patients treated with tocilizumab)) and 19 healthy controls. Consequently, the tocilizumab group exhibited lower levels than the other three groups according to the Steel-Dwass test (P<0.01). Furthermore, we compared the plasma factor XIII activity levels and the plasma factor XIII concentrations in the RA patients treated with biologics. Pearson's correlation test was used to assess the relationship between the factor XIII activity levels and the plasma factor XIII concentrations (r=0.449, P=0.019). According to the multiple regression analysis, the treatment with tocilizumab is an independent risk factor for plasma factor XIII reduction in RA patients. In conclusion, RA patients treated with tocilizumab, an IL-6R blocker, are at risk of developing acquired factor XIII deficiency. The mechanisms underlying the reduced factor XIII activity observed in RA patients treated with tocilizumab may result from the quantitative reduction in the plasma. These data imply that IL-6 plays an important role in maintaining the factor XIII activity level.
23568054 Autoimmune smoke and fire--coexisting rheumatoid arthritis and chronic obstructive pulmona 2013 Jul To assess the association between RA and chronic obstructive pulmonary disease (COPD) in a population-based case-control study. A cross-sectional analysis performed utilizing the database of Clalit Health Services, the largest healthcare provider organization in Israel. Patients over the age of 20 years who were diagnosed with RA ('cases') and who were treated with any anti-rheumatic drug were compared with a sample of age- and gender-matched enrollees ('controls') without regard for the prevalence of COPD. Data on health-related lifestyles and other comorbidities were collected. χ(2), t tests, and logistic regression models were used to compare the study groups. The study included 9,039 RA cases and 15,070 controls. The proportion of COPD was significantly higher in patients with RA as compared to the control group (8.6 vs. 4.4%, p < 0.0001, odds ratio (OR) 2.06, 95% confidence interval (CI) 1.85-2.29). A multivariate logistic regression model demonstrated that RA was significantly associated with COPD, after controlling for confounders, including age, sex, socioeconomic status, smoking, and obesity (adjusted OR 1.98, 95% CI 1.77-2.21, p < 0.0001). In this large data-based study, RA was found to be associated with COPD.
25069714 Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid arthritis patien 2014 Jul 28 BACKGROUND: KIR genes coding for natural killer cell immunoglobulin-like receptors, KIR, influence the effector and regulatory function of NK cells as well as some subpopulations of T lymphocytes (e.g. CD4+CD28-KIR+) depending on presence of ligands (particularly HLA-C molecules). KIR-KIR ligand interaction may lead to the development of autoimmune disorders, including rheumatoid arthritis (RA). However, their role in the response of RA patients to methotrexate therapy is not known. METHODS: KIR genes and KIR-ligand (HLA-C C1/C2 allomorphs) genotyping was performed using the PCR-SSP method in 312 RA patients (179 classified as good responders and 133 as poor responders using DAS28 criteria). Thus, we evaluated the association of KIR genes and HLA-C allomorphs with the response to methotrexate (MTX) treatment. RESULTS: We observed that patients possessing the full-length KIR2DS4 (KIR2DS4f) gene had a lower chance of responding in comparison to KIR2DS4f-negative cases. This phenomenon was observed both in erosive disease (ED) and rheumatoid factor (RF) positive and in ED- and RF-negative patients. Interestingly, the observed effect of the KIR2DS4f gene was strongest in individuals possessing medium values (20-33 mm/h) of the erythrocyte sedimentation rate (ESR). Patients with high ESR values had low probability and, in contrast, patients with low ESR had a high probability of MTX response, and the presence of KIR2DS4f did not affect their outcome. Additionally, we show that the KIR2DS4f effect did not depend on the presence of either C1 or C2 allomorphs. CONCLUSION: Our results suggest that the response of RA patients with medium ESR values to MTX treatment may be dependent on the full-length KIR2DS4 gene.
24794149 Clinically important changes in individual and composite measures of rheumatoid arthritis 2015 Sep OBJECTIVE: Thresholds of minimal clinically important improvement (MCII) are needed to plan and interpret clinical trials. We estimated MCIIs for the rheumatoid arthritis (RA) activity measures of patient global assessment, pain score, Health Assessment Questionnaire Disability Index (HAQ), Disease Activity Score-28 (DAS28), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). METHODS: In this prospective longitudinal study, we studied 250 patients who had active RA. Disease activity measures were collected before and either 1 month (for patients treated with prednisone) or 4 months (for patients treated with disease modifying medications or biologics) after treatment escalation. Patient judgments of improvement in arthritis status were related to prospectively assessed changes in the measures. MCIIs were changes that had a specificity of 0.80 for improvement based on receiver operating characteristic curve analysis. We used bootstrapping to provide estimates with predictive validity. RESULTS: At baseline, the mean (±SD) DAS28-ESR (erythrocyte sedimentation rate) was 6.16±1.2 and mean SDAI was 38.6±14.8. Improvement in overall arthritis status was reported by 167 patients (66.8%). Patients were consistent in their ratings of improvement versus no change or worsening, with receiver operating characteristic curve areas ≥0.74. MCIIs with a specificity for improvement of 0.80 were: patient global assessment -18, pain score -20, HAQ -0.375, DAS28-ESR -1.2, DAS28-CRP (C-reactive protein) -1.0, SDAI -13, and CDAI -12. CONCLUSIONS: MCIIs for individual core set measures were larger than previous estimates. Reporting the proportion of patients who meet these MCII thresholds can improve the interpretation of clinical trials in RA.
23819583 Interleukin-17A: a unique pathway in immune-mediated diseases: psoriasis, psoriatic arthri 2014 Feb Experimental evidence points to the importance of the cytokine interleukin-17A (IL-17A) in the pathogenesis of several immunoinflammatory diseases including psoriasis, psoriatic arthritis and rheumatoid arthritis. Although a principal effector of T helper type 17 cells, IL-17A is produced by many other cell types including CD8(+) T cells and γδ T cells, and is found at high levels associated with mast cells and neutrophils at sites of skin and joint disease in humans. IL-17A up-regulates expression of numerous inflammation-related genes in target cells such as keratinocytes and fibroblasts, leading to increased production of chemokines, cytokines, antimicrobial peptides and other mediators that contribute to clinical disease features. Importantly, IL-17A must be considered within the context of the local microenvironment, because it acts synergistically or additively with other pro-inflammatory cytokines, including tumour necrosis factor. Several direct IL-17A inhibitors have shown promising activity in proof of concept and phase 2 clinical studies, thereby providing confirmation of experimental data supporting IL-17A in disease pathogenesis, although levels of response are not predicted by pre-clinical findings. IL-17A inhibitors produced rapid down-regulation of the psoriasis gene signature and high clinical response rates in patients with moderate-to-severe plaque psoriasis, consistent with an important role for IL-17A in psoriasis pathogenesis. Clinical response rates with IL-17A inhibitors in psoriatic arthritis and rheumatoid arthritis, however, were improved to a lesser degree compared with placebo, suggesting that IL-17A is either important in a subset of patients or plays a relatively minor role in inflammatory joint disease. Ongoing phase 3 clinical trials should provide further information on the role of IL-17A in these diseases.
24560878 Rheumatoid arthritis quality measures and radiographic progression. 2014 Aug OBJECTIVE: Documentation of quality measures (QMs) in rheumatoid arthritis (RA) is used as a surrogate for measure of quality of care, but the association of this documentation with radiographic outcomes is uncertain. We examined documentation of RA QMs, for disease activity and functional status and the association with radiographic outcomes. METHODS: Data were analyzed for 438 RA patients in a longitudinal cohort with complete data on van der Heijde-modified Total Sharp Score (TSS). All rheumatologist (N = 18) notes in the electronic medical record during a 24-month period were reviewed for RA QMs. Any mention of disease activity categorized as low, moderate, or high was considered documentation of the QM for disease activity. Functional status QM documentation included any mention of the impact of RA on function. Change in TSS was quantified with progression defined as ≥1 unit per year. We compared percent of visits with an RA QM documented and mean change in TSS. RESULTS: The mean age in the cohort was 56.9 years, disease duration was 10.8 years, baseline DAS28 score was 3.8 (±1.6), 67.7% were seropositive, and 33.9% used a biologic DMARD. Radiographic progression was observed in 28.5%. Disease activity was documented for 29.0% of patient visits and functional status in 74.7%; neither had any significant relationship to mean TSS change (both P > 0.10). CONCLUSION: The documentation of RA QMs was infrequent and not associated with radiographic outcomes over 24 months.
23811586 [Bone structure in rheumatoid arthritis]. 2013 Jul In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA.
24517054 [Research on the relationship between combined detection of RF and CCP and Chinese medical 2013 Dec OBJECTIVE: To study the objective diagnostic mechanisms on Chinese medical (CM) syndrome patterns of rheumatoid arthritis (RA), and to research different titers of rheumatoid factor (RF)/citrullinated protein antibody (CCP) in CM syndrome patterns of RA. METHODS: Totally 230 early RA patients were assigned to five CM syndrome pattern groups, i.e., the dampness-heat blockage group (50 cases), the cold-dampness blockage group (50 cases), the Shen-qi deficiency-cold group (50 cases), the Gan-Shen yin deficiency group (40 cases), and the blood stasis blockage group (40 cases). Another 100 healthy subjects were recruited as the healthy control group. RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody were detected and compared. RESULTS: The titers of RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody were higher in all groups than in the healthy control groups (P < 0.01). As for the 5 groups, RF-IGM, RF-IGA,RF-IGG, and anti-CCP antibody were higher in the RA active stage than in the nonactive stage. They were higher in the dampness-heat blockage group in the RA active stage than in the Shen-qi deficiency-cold group, the Gan-shen yin deficiency group, and the blood stasis blockage group. CONCLUSION: Titers of RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody could be taken as judging indicators for differentiating objective lab indices of CM syndromes and assessing the active stage of RA.
24644043 Alterations of bone density, microstructure, and strength of the distal radius in male pat 2014 Sep In this cross-sectional study, we investigated volumetric bone mineral density (vBMD), bone microstructure, and biomechanical competence of the distal radius in male patients with rheumatoid arthritis (RA). The study cohort comprised 50 male RA patients of average age of 61.1 years and 50 age-matched healthy males. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius provided measures of cortical and trabecular vBMD, microstructure, and biomechanical indices. aBMD of the hip but not the lumbar spine or ultradistal radius was significantly lower in RA patients than controls after adjustment for body weight. Total, cortical, and trabecular vBMD at the distal radius were, on average, -3.9% to -23.2% significantly lower in RA patients, and these differences were not affected by adjustment for body weight, testosterone level, or aBMD at the ultradistal radius. Trabecular microstructure indices were, on average, -8.1% (trabecular number) to 28.7% (trabecular network inhomogeneity) significantly inferior, whereas cortical pore volume and cortical porosity index were, on average, 80.3% and 63.9%, respectively, significantly higher in RA patients. RA patients also had significantly lower whole-bone stiffness, modulus, and failure load, with lower and more unevenly distributed cortical and trabecular stress. Density and microstructure indices significantly correlated with disease activity, severity, and levels of pro-inflammatory cytokines (interleukin [IL] 12p70, tumor necrosis factor, IL-6 and IL-1β). Ten RA patients had focal periosteal bone apposition most prominent at the ulnovolar aspect of the distal radius. These patients had shorter disease duration and significantly higher cortical porosity. In conclusion, HR-pQCT reveals significant alterations of bone density, microstructure, and strength of the distal radius in male RA patients and provides new insight into the microstructural basis of bone fragility accompanying chronic inflammation.
24049024 Ischaemic heart preconditioning in rats with adjuvant-induced arthritis. 2013 BACKGROUND: Adjuvant-induced arthritis (AIA) in rats is a model of chronic systemic inflammation and a model of rheumatoidarthritis in humans. AIM: To investigate effectiveness of ischaemic preconditioning (IPC) in reducing the area of myocardial infarction in rats with AIA. METHODS: The study was performed in vivo in male SPRD/Mol/Lod rats. Animals were assigned to the experimental group (n = 15) or the control group (n = 14). In the experimental group, AIA was induced by subcutaneous administration of 1 mLof Freund's complete adjuvant, and the experiment was performed after 14 days. In control (healthy) animals, no procedures were performed prior to the proper experiment. Animals were anaesthesized (by intraperitoneal administration of ketamineand xylazine) and put on a ventilator. Then, myocardial infarction was induced, preceded by IPC in some animals. To induceinfarction, left main coronary artery (LMCA) was occluded for 30 min, followed by 60 min of reperfusion. IPC protocol consisted of LMCA occlusion for 3 min, followed by 5 min of reperfusion and a second LMCA occlusion for 7 min. Weevaluated a percentage ratio of the infarct size to the risk area (IS/RA). Necrosis area was stained with tetrazolium, and thearea supplied by LMCA was determined using Evans blue. All areas were determined by planimetry. We used nonparametric Kruskal-Wallis rank ANOVA with multiple comparisons, and the results were shown as median values and 25th and 75th percentiles. P < 0.05 was considered statistically significant. RESULTS: In the control group with IPC (n = 7), the IS/RA ratio of 25% (23-38) was significantly reduced compared to thecontrol group without IPC (n = 7) (58% [57-63], p < 0.05). In the AIA group with IPC (n = 7), the IS/RA ratio of 58% (51-65)did not differ significantly compared to the AIA group without IPC (n = 8) (65% [62-71]). CONCLUSIONS: Our findings indicate that IPC in rats with AIA does not result in a significant reduction of myocardial necrosisarea induced by 30 min of ischaemia and 60 min of reperfusion. This effect might have been related to the presence ofchronic systemic inflammation. Absent or reduced benefits of IPC may be one reason for an increased cardiovascular risk inpatients with rheumatoid arthritis.
25046184 Palmar shelf arthroplasty for rheumatoid wrist arthritis: long-term follow-up. 2014 Jul Rheumatoid wrist arthritis is common and affects about 1.5 million people in the United States. For advanced disease, arthrodesis and implant arthroplasty have been recommended as treatment options. In 1970, palmar shelf arthroplasty was introduced, and initial results were encouraging but not reproducible. In 1990, Dr. Skoff modified the original procedure with good results in patients followed for 2 to 7 years. This study reports the results of 13 patients (9 women, 4 men; average age, 43 years) who were followed up for an average of 13.2 years (range, 10 to 20 years) after undergoing modified palmar shelf arthroplasty. The patients were interviewed and examined, and wrist radiographs were taken. The patients completed a questionnaire that used a 10-point pain analog scale and the Quick Disabilities of the Arm, Shoulder and Hand (DASH) and Modernized Activity Subjective Survey (MASS) Scoring Systems. Scoring results demonstrated improvement in pain at rest and with activity. MASS and Quick DASH scores improved by 76% (P < .001). Wrist range of motion averaged 35° extension and 32° flexion. One patient required wrist fusion; none of the remaining 12 patients required surgical revision. Patient satisfaction was very high, and radiographic results demonstrated maintenance of the radiocarpal pseudarthrosis without ankylosis. The long-term results of modified palmar shelf arthroplasty demonstrated enduring analgesia and mobility without the complications of an implant. Modified palmar shelf arthroplasty is a reasonable surgical alternative for advanced rheumatoid arthritis of the wrist.
23275079 TNF-related apoptosis-inducing ligand (TRAIL) in rheumatoid arthritis: what's new? 2014 May TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein of the TNF superfamily that serves as an extracellular signal that triggers programmed cell death in tumor cells, without affecting normal cells. Recently, scientists have turned their attention to the emerging role of TRAIL in immune and autoimmune responses. TRAIL has been shown to down-regulate the self-antigens in autoimmune diseases, such as rheumatoid arthritis (RA) by exerting its apoptotic effect on activated T cells and synoviocytes and by its local anti-inflammatory effect. The impact of TRAIL molecular variants and agonistic monoclonal antibodies in the regulation of TRAIL activity in arthritis animal models strongly supports the idea of testing the role of TRAIL in humans, with the aim of developing new effective therapies that promote apoptosis of synoviocytes and/or infiltrating lymphocytes, by targeting TRAIL. The aim of this review is to summarize recent progress and current knowledge of TRAIL functions in RA.
23597324 Painful effects of auditory startle, forehead cooling and psychological stress in patients 2013 May OBJECTIVE: The aim of this study was to determine whether the clinical pain associated with rheumatoid arthritis or fibromyalgia would increase during standard laboratory tasks and, if so, whether these increases were linked with individual differences in psychological distress. METHODS: Twenty-three patients with fibromyalgia and 16 patients with rheumatoid arthritis rated changes in clinical pain after an acoustic startle stimulus, during painful forehead cooling, and during stressful mental arithmetic. In addition, pain tolerance was assessed during a submaximal effort tourniquet test, and patients provided ratings of distress on a standard Depression, Anxiety and Stress Inventory. RESULTS: Pain at rest was associated with depression scores in patients with rheumatoid arthritis, and was associated with stress scores in the fibromyalgia group. However, pain tolerance was unrelated to individual differences in psychological distress in either group. In patients with fibromyalgia, clinical pain increased after the acoustic startle stimulus and painful forehead cooling, and increased during stressful mental arithmetic. Arthritic pain also increased during forehead cooling and mental arithmetic in association with indices of psychological distress. CONCLUSIONS: These findings suggest that processes linked with individual differences in distress aggravate pain in rheumatoid arthritis, whereas some other mechanism (e.g., failure of stress-related pain modulation processes or an aberrant interaction between nociceptive afferent and sympathetic efferent fibers) triggers stress-induced pain in fibromyalgia.
23871988 Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascula 2013 Sep 3 Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints in which systemic overproduction of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) may accelerate cardiovascular (CV) complications. Synovial inflammation in RA spreads systemically and transforms silently into chronic inflammation manifested by increased cytokine release and abnormally high levels of acute reactive proteins (ARPs) such as C-reactive protein (CRP), suggesting inflammation as a connecting link between RA and CV dysfunction. While the treatment to improve CV function in RA patients is being validated, it is timely to propose and test two-pronged therapies that ameliorate arthritis concomitant to improving CV functions. In this review, we summarized the pre-clinical and clinical studies validating the cardiovascular and anti-rheumatic activities of epigallocatechin-3 gallate (EGCG), a potent anti-inflammatory molecule found in green tea. The review also draws many parallels that have emerged between the paradigm of cytokine-driven inflammation in the pathogenesis of RA and its CV complications. Finally, based on extensive clinical evidence of the 'synovial inflammation-systemic inflammation' link and the benefits of EGCG in regulating these two pathologies via common driving factors, authors put forward an argument that EGCG may be tested for its potential CV benefit along with anti-rheumatic activity in animal models of human RA.
23976944 Automatic prediction of rheumatoid arthritis disease activity from the electronic medical 2013 OBJECTIVE: We aimed to mine the data in the Electronic Medical Record to automatically discover patients' Rheumatoid Arthritis disease activity at discrete rheumatology clinic visits. We cast the problem as a document classification task where the feature space includes concepts from the clinical narrative and lab values as stored in the Electronic Medical Record. MATERIALS AND METHODS: The Training Set consisted of 2792 clinical notes and associated lab values. Test Set 1 included 1749 clinical notes and associated lab values. Test Set 2 included 344 clinical notes for which there were no associated lab values. The Apache clinical Text Analysis and Knowledge Extraction System was used to analyze the text and transform it into informative features to be combined with relevant lab values. RESULTS: Experiments over a range of machine learning algorithms and features were conducted. The best performing combination was linear kernel Support Vector Machines with Unified Medical Language System Concept Unique Identifier features with feature selection and lab values. The Area Under the Receiver Operating Characteristic Curve (AUC) is 0.831 (σ = 0.0317), statistically significant as compared to two baselines (AUC = 0.758, σ = 0.0291). Algorithms demonstrated superior performance on cases clinically defined as extreme categories of disease activity (Remission and High) compared to those defined as intermediate categories (Moderate and Low) and included laboratory data on inflammatory markers. CONCLUSION: Automatic Rheumatoid Arthritis disease activity discovery from Electronic Medical Record data is a learnable task approximating human performance. As a result, this approach might have several research applications, such as the identification of patients for genome-wide pharmacogenetic studies that require large sample sizes with precise definitions of disease activity and response to therapies.
23334372 Inhibition of JNK in synovium by treatment with golimumab in rheumatoid arthritis. 2014 Jan The aim of this study was to investigate immunohistological changes in mitogen-activated protein kinases (MAPKs) in the synovium following treatment with golimumab, compared with methotrexate (MTX). We assessed synovial tissues for 13 different molecules to detect cytokine levels histologically from 10 methotrexate (MTX)-treated rheumatoid arthritis (RA) patients as controls and 10 golimumab plus MTX-treated RA patients. Synovium samples from both groups were assessed by hematoxylin and eosin (HE) staining and analyzed for expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), CD4 (T cells), CD8 (T cells), CD20 (B cells), CD68 (macrophages), receptor activator of nuclear (kappa) B ligand (RANKL), bromodeoxyuridine (BrdU), CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (ERK1/ERK2), and phospho-c-Jun N-terminal kinase (JNK), by an immunohistological examination. HE staining showed that there was a significant decrease in cell proliferation in the synovium in RA patients who received golimumab compared with the controls. TNF-α, IL-6, MMP3, BrdU, p38, and ERK were not seen at significant levels in either group. On the other hand, CD4, CD8, CD20, CD29, CD68, RANKL, and JNK were significantly decreased in the golimumab group compared with the control. Based on a histological analysis of the synovium, it appears that the efficacy of the treatment with golimumab may involve the inhibition of cell proliferation, with decreases in T cells, B cells, macrophages, β-1 integrin, RANKL, and JNK in the synovium, compared with MTX treatment, in RA.
24599677 Visualization of DAS28, SDAI, and CDAI: the magic carpets of rheumatoid arthritis. 2014 May There has been continuous debate regarding the applicability of various composite measures for the assessment of disease activity in rheumatoid arthritis (RA). In order to further dissect this issue, we numerically and graphically modeled 28-joint disease activity scale (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) by three-dimensional (3D) plotting. We wished to graphically visualize the relative contribution of various elements in the three activity indices to each other. We calculated DAS28 (3 variables), SDAI, and CDAI by the standard equations. We plotted 3D "carpets" showing all combinations of the corresponding variables yielding to DAS28 = 5.1, DAS28 = 3.2, DAS28 = 2.6, SDAI = 26, SDAI = 11, and SDAI = 3.3. We also plotted the 3D carpet for CDAI. In patients with high or moderate disease activity, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was not a major confounding factor when calculating DAS28 and SDAI, respectively. In contrast, ESR and CRP highly overshadowed changes in joint counts and global assessments in patients with low disease activity (LDA) or those in remission. No reliable assessment of LDA can be performed in cases where ESR >54 mm/h or CRP >20 mg/dl. Similarly, remission cannot be determined if ESR >19 mm/h or CRP >5 mg/dl. As CDAI does not include acute phase reactants, CDAI may be a useful tool even in states of remission or LDA. Our results suggest that acute phase reactants are indeed major confounding factors and should be omitted when assessing RA disease activity at least in special cases.