Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
---|---|---|---|---|
18636308 | Limited results of group self-management education for rheumatoid arthritis patients and t | 2008 Dec | This study aimed to identify the reasons for limited results of group self-management for RA patients and their partners from the patient perspective. Semi-structured interviews with ten male and ten female patients who had participated in group self-management with or without their partner were content analyzed with respect to motivation to participate and the effects of the program on them. The limited effects of the self-management program appear to be linked with low motivation to participate and to change health behavior. The data show that a decline in health and also stressful life events might be associated with the disappointing effects of the program. Three strategies were proposed for improving the program's effects: (a) provide information about the program in advance to ensure that patients have appropriate expectations. (b) Enhance intrinsic motivation to change health behavior by counseling techniques. (c) Tailoring with respect to motivation and current concerns could help to form more homogeneous groups or could be the basis for a tailored online intervention. | |
16691500 | Altered expression and glycosylation of plasma proteins in rheumatoid arthritis. | 2006 May | Altered glycosylation of plasma proteins has been directly implicated in the pathogenesis of rheumatoid arthritis (RA). The present study investigated the changes in the Concanavalin-A (Con-A)-bound plasma proteins in the RA patients in comparison to that of the healthy controls. Two proteins (MW approximately 32 kDa and approximately 62 kDa) showed an alteration in expression while an altered monosaccharide profile (high mannose) was observed in the approximately 62 kDa protein in the samples collected from RA patients. The 2-dimensional polyacrylamide gel electrophoresis analysis of the Con-A-bound plasma samples showed a large number of protein spots, a few of which were differentially expressed in the RA patients. Some unidentified proteins were detected in the RA patients which were absent in the control samples. The present study, therefore, enunciates the role of carbohydrates as well as that of the acute phase response in the disease pathogenesis. | |
18534502 | Total hip arthroplasty in the underweight. | 2008 Oct | The outcomes of 20 patients diagnosed with osteoarthritis or rheumatoid arthritis with body mass index less than 18.5 (considered underweight) who received total hip arthroplasty at a single institution were reviewed. Surgical complications in the first 30 days after surgery included 1 prolonged surgical site drainage and 3 posterior dislocations. Two patients experienced medical complications that included hematemesis, confusion, aspiration pneumonia, and death. Sixty-five percent of the patients received at least one blood transfusion. Harris hip scores improved from 35 to 81 (P < .05) at an average of 6.1 years (2-10.1 years) of follow-up. Total hip arthroplasty is effective in patients who are underweight; however, they appear to be at an increased risk of dislocation and blood transfusion. | |
18467370 | Hypertension in rheumatoid arthritis. | 2008 Sep | RA associates with an increased burden of cardiovascular disease, which is at least partially attributed to classical risk factors such as hypertension (HT) and dyslipidaemia. HT is highly prevalent, and seems to be under-diagnosed and under-treated among patients with RA. In this review, we discuss the mechanisms that may lead to increased blood pressure in such patients, paying particular attention to commonly used drugs for the treatment of RA. We also suggest screening strategies and management algorithms for HT, specific to the RA population, although it is clear that these need to be formally assessed in prospective randomized controlled trials designed specifically for the purpose, which, unfortunately, are currently lacking. | |
16562833 | Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis. | 2006 Mar | Turmeric has been used for centuries in Ayurvedic medicine as a treatment for inflammatory disorders including arthritis. On the basis of this traditional usage, dietary supplements containing turmeric rhizome and turmeric extracts are also being used in the western world for arthritis treatment and prevention. However, to our knowledge, no data are available regarding antiarthritic efficacy of complex turmeric extracts similar in composition to those available for use as dietary supplements. Therefore, the studies described here were undertaken to determine the in vivo efficacy of well-characterized curcuminoid-containing turmeric extracts in the prevention or treatment of arthritis using streptococcal cell wall (SCW)-induced arthritis, a well-described animal model of rheumatoid arthritis (RA). Arthritic index, a clinical measure of joint swelling, was used as the primary endpoint for assessing the effect of extracts on joint inflammation. An essential oil-depleted turmeric fraction containing 41% of the three major curcuminoids was efficacious in preventing joint inflammation when treatment was started before, but not after, the onset of joint inflammation. A commercial sample containing 94% of the three major curcuminoids was more potent in preventing arthritis than the essential oil-depleted turmeric fraction when compared by total curcuminoid dose per body weight. In conclusion, these data (1) document the in vivo antiarthritic efficacy of an essential oil-depleted turmeric fraction and (2) suggest that the three major curcuminoids are responsible for this antiarthritic effect, while the remaining compounds in the crude turmeric extract may inhibit this protective effect. | |
17513783 | Soluble TNF-like cytokine (TL1A) production by immune complexes stimulated monocytes in rh | 2007 Jun 1 | TNF-like cytokine (TL1A) is a newly identified member of the TNF superfamily of ligands that is important for T cell costimulation and Th1 polarization. However, despite increasing information about its functions, very little is known about expression of TL1A in normal or pathological states. In this study, we report that mononuclear phagocytes appear to be a major source of TL1A in rheumatoid arthritis (RA), as revealed by their strong TL1A expression in either synovial fluids or synovial tissue of rheumatoid factor (RF)-seropositive RA patients, but not RF-/RA patients. Accordingly, in vitro experiments revealed that human monocytes express and release significant amounts of soluble TL1A when stimulated with insoluble immune complexes (IC), polyethylene glycol precipitates from the serum of RF+/RA patients, or with insoluble ICs purified from RA synovial fluids. Monocyte-derived soluble TL1A was biologically active as determined by its capacity to induce apoptosis of the human erythroleukemic cell line TF-1, as well as to cooperate with IL-12 and IL-18 in inducing the production of IFN-gamma by CD4(+) T cells. Because RA is a chronic inflammatory disease with autoimmune etiology, in which ICs, autoantibodies (including RF), and various cytokines contribute to its pathology, our data suggest that TL1A could be involved in its pathogenesis and contribute to the severity of RA disease that is typical of RF+/RA patients. | |
16247584 | Evaluation of dynamic postural balance using the Biodex Stability System in rheumatoid art | 2006 Jul | The aim of this study was to investigate dynamic postural balance in patients with rheumatoid arthritis (RA) in relation to the disease characteristics. Seventy-four patients with RA and 42 controls of the same age group were tested using the Biodex Stability System (Biodex Medical Systems, Shirley, NY, USA). Anterior/posterior (AP), medial/lateral (ML), and overall (OA) indices were obtained with bilateral stance at platform stabilities of 2 and 8. Subjects were tested with "eyes open" at all times. At the same time, Disease Activity Score, functional disability [Health Assessment Questionnaire, (HAQ)], and Steinbrocker Functional Class (SFC) were assessed. Both the AP and OA indices in the RA group were significantly higher than in the control group for level 8. For OA index, the results were 2.7+/-0.9 in RA and 2.2+/-0.7 in the control group (p=0.006), and for AP index, the results were 2.1+/-0.7 in RA and 1.7+/-0.6 in the control group (p=0.002). Eleven patients (15.9%) and three controls (7.1%) could not complete the test at level 2. When the patients and controls who completed the test were compared, a significant difference was found only in the ML index. The results were 4.6+/-2.4 in RA and 3.8+/-1.6 in the control group (p=0.047). A positive correlation between HAQ and postural balance for all three stability indices at level 8 was detected. A positive correlation between SFC and postural balance for OA and ML at level 8 was also found. Multiple linear regression analyses revealed age and body mass index (BMI) to be the most important factors influencing postural dynamic balance at both levels in the RA group and in healthy controls. RA has a negative effect on dynamic postural stability. The functional status affects dynamic balance more than disease activity. Age and BMI were the most important factors influencing postural dynamic balance in the RA group and in healthy controls. Level 2 does not appear to be an appropriate level for evaluating postural stability in RA. | |
17442097 | Developments in the synovial biology field 2006. | 2007 | Synovial pathophysiology is a complex and synergistic interplay of different cell populations with tissue components, mediated by a variety of signaling mechanisms. All of these mechanisms drive the affected joint into inflammation and drive the subsequent destruction of cartilage and bone. Each cell type contributes significantly to the initiation and perpetuation of this deleterious concert, especially in rheumatoid arthritis. Rheumatoid arthritis synovial fibroblasts and macrophages, both cell types with pivotal roles in inflammation and destruction, but also T cells and B cells are crucial for complex network in the inflamed synovium. An even more complex cellular crosstalk between these key players maintains a process of chronic inflammation. As outlined in the present review, in the past year substantial progress has been made to elucidate further details of the rich pathophysiology of rheumatoid arthritis, which may also facilitate the identification of novel targets for future therapeutic strategies. | |
17278019 | Retrospective clinical study on the notable efficacy and related factors of infliximab the | 2007 | This study aims to reconfirm the clinical efficacy and related factors of infliximab therapy, the first biological agent introduced to Japanese patients with rheumatoid arthritis (RA). Data of 351 RA patients with infliximab were collected retrospectively from three major centers for management of rheumatic diseases in Japan. Infliximab was infused according to the approved method, and the clinical response was evaluated following 22 weeks of infliximab therapy in 258 patients using the European League Against Rheumatism (EULAR) response criteria. DAS28-CRP (Disease Activity Score including a 28-joint count/C-reactive protein) with a threshold of 4.1 or 2.7 for the high or low disease activity cut-off was also used. A total of 90.3% of patients exhibited high disease activity before infliximab therapy. After 22 weeks of infliximab therapy, the proportions of patients exhibiting high activity, moderate activity, low activity, or in clinical remission were 27.9%, 33.3%, 10.9%, or 27.9%, respectively, thereby indicating good overall efficacy of infliximab therapy. A good or moderate overall response to therapy was achieved in 84.5% of patients. Male sex, rheumatoid factor (RF) negativity, low CRP, lower swollen joint count and a low prednisolone dose were significantly related to the clinical response. Furthermore, male sex, older age, and a high tender joint count had a significant correlation with treatment discontinuation as a result of adverse reactions. In conclusion, we have reconfirmed the effectiveness of infliximab in Japanese patients with RA by using DAS28-CRP and EULAR response criteria. These data will facilitate more efficacious use of this expensive biological agent in the daily practice of rheumatology in Japan. | |
18708166 | A new strategy for the early diagnosis of rheumatoid arthritis: a combined approach. | 2009 Jan | Rheumatoid arthritis [RA] is one of the most common and severe autoimmune rheumatic diseases, diagnosed primarily according to clinical manifestations and radiological reports. For many years, laboratory diagnosis of rheumatoid arthritis has relied on the detection of rheumatoid factor [RF], as established by the ACR criteria. A recent test to detect antibodies towards citrullinated peptides, called the anti-CCP assay, showed a similar sensitivity but a more elevated specificity than the RF test. Our intention was the recognition of an optimal diagnostic strategy that exhibits the highest sensitivity and specificity for RA detection. To this purpose, we examine the usefulness of autoantibodies in RA testing, evaluating the diagnostic performance of conventional and innovative assays for RF detection, and ELISA anti-CCP test, for anti-CCP antibodies detection, by a prospective study. Multiplex cytofluorimetric test appeared to be more sensitive and specific than nephelometric assay for RF detection. Hence, a novel combined approach, significantly increasing the diagnostic sensitivity for RA, was planned, employing the multiplex RF test in combination with the anti-CCP test. | |
17985420 | Treatment of recent-onset rheumatoid arthritis: lessons from the BeSt study. | 2007 Nov | OBJECTIVE: To determine the efficacy, toxicity, utilities, and costs of 4 treatment strategies for patients with recent-onset rheumatoid arthritis (RA). METHODS: 508 patients with recent-onset active RA [mean Disease Activity Score (DAS) 4.4, mean Health Assessment Questionnaire score 1.4] were randomized into 4 strategy groups: (1) sequential monotherapy; (2) step-up to combination therapy [both starting with methotrexate (MTX)]; (3) initial combination therapy with MTX, sulfasalazine, and prednisone; (4) initial combination therapy with MTX and infliximab. Treatment adjustments were based on 3-monthly calculations of the DAS (target DAS ? 2.4), by research nurses who were blinded to the strategy group. They also collected data on treatment toxicity, functional ability, costs, and utilities. Yearly anonymized radiographs of hands and feet were scored in random order by 2 independent physicians, using the Sharp/van der Heijde score. RESULTS: Functional ability improved significantly earlier in Groups 3 and 4 than in Groups 1 and 2, but was comparable among the groups at the end of the first year of treatment. Radiographic joint damage progression was significantly lower in Groups 3 and 4 than in Groups 1 and 2, but low in all groups compared to other RA populations, probably due to DAS-driven treatment adjustments in all groups. More patients in Groups 3 and 4 than in Groups 1 and 2 achieved clinical remission (DAS 1.6), and patients who achieved early continued remission in Groups 3 and 4 had significantly less joint damage progression than those who achieved the same in Groups 1 and 2. More patients could taper and stop all antirheumatic drugs and still retained remission in Group 4 (17% at t = 3 years) than in the other groups (10%, 5%, 9%, respectively). Toxicity was comparable between groups. Quality of life measures were significantly higher in Group 4 than in the other groups, but costs of treatment were also the highest in Group 4. Depending on the method used, higher productivity in Group 4 compensated for the higher medical costs. CONCLUSION: In patients with recent-onset RA, initial combination therapy including prednisone or infliximab results in earlier clinical improvement and less joint damage progression than initial monotherapy. Initial treatment with infliximab resulted in the highest quality of life, highest productivity, and highest medical costs. DAS-driven treatment adjustments were effective to suppress disease activity and damage progression in all groups. | |
16569685 | Serum immunoglobulin free light chain assessment in rheumatoid arthritis and primary Sjogr | 2007 Jan | BACKGROUND: B cell activation may result in an increased secretion of immunoglobulin free light chains (FLCs) in autoimmune diseases. OBJECTIVE: To analyse serum FLC levels in patients with rheumatoid arthritis and in those with primary Sjögren's syndrome (pSS). PATIENTS AND METHODS: Blood samples were collected from 80 healthy blood donors, 50 patients with rheumatoid arthritis and 139 patients with pSS. Serum FLC level was measured using a new quantitative immunoassay. RESULTS: Mean (standard error (SE)) serum kappa and lambda FLC levels were significantly higher in patients with rheumatoid arthritis and in those with pSS than in controls (kappa : 18.9 (1.1) and 16.3 (1.4) v 10.5 (0.4) mg/l, p<0.001 and p = 0.001, respectively; lambda: 16.7 (1.2) and 19.3 (1.5) v 11.6 (0.6) mg/l, p<0.001 for both). 18 (36%) patients with rheumatoid arthritis and 31 (22.3%) patients with pSS had abnormal serum FLC levels (increased kappa or lambda levels and abnormal ratio of kappa:lambda). Serum kappa and lambda levels were correlated with other B cell activation markers in both diseases. FLC levels increased with disease activity, because, unlike total gammaglobulin and immunoglobulin G levels, they were significantly correlated with Disease Activity Score 28 in patients with rheumatoid arthritis (p = 0.004 for kappa, p = 0.05 for lambda) and with extraglandular involvement in pSS (p = 0.01 for kappa, p = 0.04 for lambda). CONCLUSION: FLC levels are increased and correlate with disease activity in patients with rheumatoid arthritis and in those with pSS, two diseases in which increased risk of lymphoma could result from persistent B cell activation and disease activity. Further studies are required to determine whether FLC assessment could represent a relevant biomarker for response to treatment (especially B cell depletion) and for the risk of lymphoma in autoimmune diseases. | |
19102090 | [Undesirable effects of methothrexate during treatment of rheumatoid arthritis]. | 2007 | INTRODUCTION: Methotrexate used as antimetabolite since 40 years in cancerology, is curretly pointed out at weak dose in the treatment of rheumatoid arthitis. However, the intervening of undesirable effects is currently the principal factor limiting its use. The main of our study was evaluate the nature and the frequency of undesirable effects during treatement of rhumatoid arthritis by methotrexate in a prospective study in the department of internal medecine of A.L.D hospital. MATERIAL AND METHODS: Fifty patients were included in the study, they were 43 female and 7 male (sex ratio of 0.161).The mean age were 40.8 years, ranging from 18 to 68. The mean last of MTX treatment was 16.58 months, ranging from 1 to 64. RESULTS: Twenty seven patients (54%) had at least one undesirable effect. Undesirable effect appeared early in 74.1%. they were 61.5% when MTX was associated with others drugs versus 27.3% when MTX was used alone. Undesirable effects mostly were digestives (38%), general (30%), mucouscutaneous (8%) and hepatics (2%).for patients undesirable effects had involved. They were responsable of definitive stopping treatment in two cases of pulmonary tuberculosis. | |
17996676 | Decreased ex vivo production of TNF-alpha and IL-8 by peripheral blood cells of patients w | 2007 Dec 15 | Monoclonal antibody against TNF-alpha such as infliximab has shown clinical efficacy in controlling the inflammatory signs and symptoms of rheumatoid arthritis (RA), but the detailed immunotherapeutic mechanism is not fully understood. We investigated 19 patients with active RA who were treated with infliximab (3 mg/kg) at weeks 0, 2, 6 and 14. Peripheral blood was obtained from the patients at weeks 0 and 14 and cultured with mitogens phytohaemagglutinin (PHA) and lipopolysaccharide (LPS). The concentrations of cytokines and soluble adhesion molecules (sICAM-1, sICAM-3, sE-selectin, sP-selectin, sVCAM-1 and sPECAM-1) in supernatant fluids or plasma were measured by flow cytometry and ELISA. After infliximab treatment, the absolute and percentage increases in release of inflammatory cytokine TNF-alpha and potent neutrophil chemoattractant IL-8 upon PHA and LPS activation were significantly decreased when compared to those of before treatment (all P<0.01). The increased releases of IL-6, IL-1beta, IL-18 and IL-12 upon mitogen activation were similar before and after infliximab treatment (all P>0.05). Plasma concentrations of these cytokines and soluble adhesion molecules did not differ significantly before and after infliximab treatment. Our study suggests that the reduction in synovial inflammation may be due to the decreased production of TNF-alpha and IL-8, and hence the number of neutrophils and other pro-inflammatory leukocytes infiltrating into the inflamed sites. | |
16412378 | Identification of citrullinated eukaryotic translation initiation factor 4G1 as novel auto | 2006 Mar 3 | Antibodies against citrullinated proteins are highly specific for rheumatoid arthritis. We previously reported that functional variants of the gene encoding peptidylarginine deiminase type 4 were closely associated with RA. The purpose of this study was to investigate the citrullinated autoantigens recognized by serum samples from patients with RA. The human chondrocyte cDNA expression library was citrullinated by PADI4 and was immunoscreened with anti-modified citrulline antibodies and sera from patients with rheumatoid arthritis. One immunoreactive cDNA clone containing a 2480-base pair insert was isolated and sequence analysis revealed that the cDNA included a part of the eukaryotic translation initiation factor 4G1. Immunoreactivity against a recombinant citrullinated eIF4G1 fragment was observed with high specificity in 50.0% of RA patients. The levels of antibodies against citrullinated eIF4G1 were correlated with those of anti-CCP antibodies. Citrullinated eIF4G1 was identified as a candidate citrullinated autoantigen in RA patients. Citrullination of eIF4G1 may thus be involved in the pathogenesis of RA. | |
16557465 | Suppression of collagen-induced arthritis by oral administration of the citrus flavonoid h | 2006 Apr | The preventive and therapeutic effects of the Citrus flavonoid hesperidin (HES) on the development of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA), were investigated. Mice were administered orally HES three times a week starting from either the onset (day 21) of secondary immunization or on day 31, when the CIA development had reached a plateau. In both cases, treatment with HES resulted in a significant suppression of clinical scores and improvement of histological features. These results suggest that oral administration of HES could be effective for treating human RA patients. | |
18395775 | High adiponectin and adiponectin receptor 1 expression in synovial fluids and synovial tis | 2009 Jun | OBJECTIVES: The major objectives of this article are first to measure the levels of expression of adiponectin and its 2 receptors (adipoR1 and adipoR2) in the peripheral blood mononuclear cells and in the synovial compartment of rheumatoid arthritis (RA) patients, and second, to assess their pro-inflammatory potential. Osteoarthritis patients and healthy subjects served as controls. METHODS: Expression of adiponectin, adipoR1, and adipoR2 were assayed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistology. The potential pro-inflammatory activity of adiponectin was studied by adding recombinant adiponectin to cultures of synovial fibroblasts. RESULTS: Immunohistology showed that numerous cells in the synovial biopsies of RA expressed adiponectin, adipoR1, and adipoR2. The synovial fibroblasts were distinctly rich in adiponectin. As expected, high adiponectin levels were present in the synovial fluids. In contrast to the synovial compartment, in peripheral blood mononuclear cells, only adipoR1 exceeded those of osteoarthritis and healthy subjects. When recombinant adiponectin was added to cultures of synovial fibroblasts, it induced up to 8.1- and 11.4-fold increase in the release of monocyte chemoattractant protein-1 and interleukin-6. CONCLUSIONS: The adiponectin adipokine axis might play a role in RA. | |
17260396 | Low-field musculoskeletal MRI. | 2007 Feb | Since it was first introduced in the field of medical imaging in the early 1980s, MRI has become essential for the diagnosis and treatment of musculoskeletal conditions. Most imaging in the United States is performed on high-field (>1.0T), whole-body scanners. However, for reasons discussed below, imaging at low (<0.5T) and medium (0.5-1.0T) field strengths using small, low-cost, easily installed scanners in imaging centers and physicians' offices is gaining increasing popularity. Such scanners can be very useful for imaging the upper and lower extremities, from the shoulder to the fingers and the hips to the toes. In this review we provide an overview of the different available extremity scanners and their advantages and disadvantages, briefly review the literature regarding their use, and discuss our experience in using low-field extremity scanners to evaluate joints. | |
18581158 | Sinusitis: a possible link with adalimumab. | 2008 Sep | The experience with anti-TNF agents is relatively short; and with time, we are learning more about the frequency of occurrence of different adverse events as the original trials were either too small or too brief. We report a case series of four patients who suffered from chronic inflammatory arthritis [rheumatoid arthritis (n = 3) and psoriatic arthritis (n = 1)]. Their inflammatory arthritis remained refractory to increasing doses of methotrexate up to 20 mg weekly and required an advance in treatment to TNF antagonists. However, within a few weeks of commencing these patients on adalimumab, they developed newly diagnosed recurring sinusitis. All these patients were assessed by otorhinolaryngologists, and had clinically confirmed diagnosis. The sinusitis remained refractory to standard medications; however, it resolved after the discontinuation of adalimumab. Although FDA and Irish Pharmaceutical Health Association describe that adalimumab use increases the risk of non-serious infections marginally and most of the patients continued on Humira (adalimumab) after the infection was resolved, however, our recent observation raises the concern of probable higher incidence. | |
19075915 | Recent patents of gene sequences relative to the phosphatidylinositol 3-kinase/Akt pathway | 2007 | Phosphoinositide 3-kinases (PI3Ks) play an essential role in the signal transduction events initiated by the binding of extracellular signals to their cell surface receptors. There are eight known PI3Ks in humans, which have been subdivided into three classes (I-III). The class I(A) of PI3K comprises the p110alpha, p110beta and p110delta isoforms, which associate with receptor tyrosine kinases (RTKs). On the other hand, the class I(B) PI3K p110gamma is regulated by G-protein-coupled receptors (GPCRs). Gene targeting studies in mice have revealed specific biological functions for the class I(A) p110delta in lymphocyte activation, and the class I(B) p110gamma in inflammatory cell responses. In human cancer, recent reports have described activating mutations in the PIK3CA gene encoding p110alpha, and inactivating mutations in the PTEN gene, a tumor suppressor and antagonist of the PI3K pathway. Thus, individual PI3K isoforms are potential drug targets for a variety of human diseases, including allergies, cancer, rheumatoid arthritis and arterial thrombosis. In this review, we will discuss recent patents relating to class I PI3Ks, including patents on the cDNA sequences of p110gamma and p110delta. Moreover, we will review patents on novel pharmacological PI3K inhibitors and on methods of manipulating T cell responses through PI3K. |