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

ID PMID Title PublicationDate abstract
20617525 Identification of the oxidative stress-related gene MSRA as a rheumatoid arthritis suscept 2010 Nov OBJECTIVE: Genome-wide association studies carried out in rheumatoid arthritis (RA) have led to the discovery of several genetic associations with this disease. Still, the current associated genetic variations can explain only part of the genetic risk involved in RA, and it is well recognized that these genome-wide association studies are likely underpowered to detect all common disease variants. This study was undertaken to explore the genomic regions showing low-significance associations in previous genome-wide association studies of RA. METHODS: To reduce the false-positive signal fraction, we exploited pathway analysis to prioritize regions containing genes most likely to be implicated in RA. We hypothesized that true disease genes would be in a similar pathway. Therefore, genes from similar pathways but located in different regions were prioritized for replication using Prioritizer software. A total of 384 genetic variants selected from previous RA genome-wide association studies were tested in a Spanish case-control discovery cohort comprising 376 RA patients and 478 healthy controls for replication. Statistically significant associations were further validated in replication cohorts from Spain and The Netherlands. The study consisted of a total of 1,818 RA patients and 2,498 controls. RESULTS: We detected a novel genetic association between RA and the MSRA gene (rs10903323) in the Spanish combined population (P = 2.91 × 10(-5) , odds ratio [OR] 1.51). This association was further tested in our independent Dutch replication cohort. Combined analysis showed an overall association of MSRA with RA (P = 3.19 × 10(-4) , OR 1.28). CONCLUSION: Our findings indicate that a novel association in the MSRA gene is related to oxidative stress and support the notion of a major role for this process in RA.
20663404 Rheumatologists' recommended patient information when prescribing methotrexate for rheumat 2010 Jul OBJECTIVES: Accurate communication of information concerning the risks and benefits of medications is essential for adherence and patient safety. A diverse array of information and sources makes it difficult to know exactly what to tell a patient with rheumatoid arthritis about methotrexate. OBJECTIVE: Our objective is to determine what key information patients must know about methotrexate and the key reasons they should call their doctor while they are taking methotrexate. METHODS: Three hundred and forty-four Canadian rheumatologists were sent a survey containing open-ended questions to gain uncued narrative perspectives from each individual's experience. The survey was designed to determine what must all patients taking methotrexate know and when must patients taking methotrexate call a physician? Emergent coding was used to establish a set of categories to form a checklist for coding. A second member checking survey was sent to gain confirmation and validation of themes developed from the initial survey. RESULTS: One hundred and seventy out of 344 (49.5%) surveys were completed. Regular blood testing, once weekly dosing, risk of infection, pregnancy and lactation information, alcohol limitation, potential lung toxicity, and drug interactions were thought to be important. Patients should call if they became pregnant, developed symptoms suggestive of lung toxicity, developed an infection, severe mouth sores, or were concerned about any side effects warranting the discontinuation of the medication. CONCLUSIONS: This study is the first to describe, from a rheumatologist's perspective, the key important information that all patients should know and when patients should call their doctor when taking methotrexate.
20307460 Use of the modified Stainsby procedure in correcting severe claw toe deformity in the rheu 2009 Jun INTRODUCTION: In claw toe deformity, the plantar plate of the metarsophalangeal joint becomes displaced onto the dorsal aspect of the metatarsal head. The Stainsby procedure replaces the displaced plantar plate to its correct position beneath the metatarsal head. OBJECTIVE: In this study we assess the efficacy of a modified Stainsby procedure for the treatment of claw toe deformity. METHODS: Thirteen patients were operated on between 2002 and 2008. Eleven patients (13 feet) were available for review with the average follow-up period being 16 months. Clinical examination was performed and AOFAS forefoot scores were measured. RESULTS: All 13 (100%) of the feet operated on had severe or moderate pain preoperatively. None had significant pain at review. Plantar callosities were reduced from 13 (100%) feet preoperatively to 1 (9%) foot postoperatively. The AOFAS forefoot score in the eleven patients improved significantly by 40.7 points from a preoperative mean of 20.1 to a mean of 50.2 at review (p<0.001). Ten (91%) of the 11 patients were completely satisfied with the procedure, 1 patient was satisfied with some reservations. CONCLUSION: This study demonstrates the modified Stainsby procedure to be effective in correcting claw toe deformity in the rheumatoid patient. It relieves pain, skin callosities and improves overall forefoot function.
20724311 Multinational evidence-based recommendations on how to investigate and follow-up undiffere 2011 Jan OBJECTIVE: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. CONCLUSIONS: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.
19265346 Screening and treatment of glucocorticoid-induced osteoporosis in rheumatoid arthritis pat 2009 Mar BACKGROUND: Despite increased awareness of glucocorticoid-induced osteoporosis, physicians are not providing recommended screening and treatment. The number of patients receiving bone density measurements, primary prevention, and secondary treatment remains low. OBJECTIVES: To analyze physician adherence of rheumatologists in an urban multispecialty group to the American College of Rheumatology 2001 ad hoc committee guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis in patients with rheumatoid arthritis (RA). METHODS: The practice evaluated is a multispecialty practice in an urban setting affiliated with a teaching hospital. A retrospective chart review was performed. The names of 428 patients with RA were obtained by billing query. One hundred thirty-six charts met criteria for final analysis. Charts were reviewed for long-term corticosteroid use >or=5 mg/d for >or=6 months, baseline bone density scans, use of calcium and vitamin D, use of hormone replacement therapy, use of calcitonin, and use of a bisphosphonate. RESULTS: 59.7% of patients qualified as long-term corticosteroid users. Only 37% of long-term corticosteroid users received baseline bone density scans. Bone loss was documented in 70.4% of corticosteroid users who received baseline DEXA scans. Only 38.9% of long-term corticosteroid users received the recommended treatment of bisphosphonates or HRT with calcium plus vitamin D according to ACR guidelines. CONCLUSIONS: Less then 40% of long-term corticosteroid users with RA received recommended DEXA scanning and treatment in a multispecialty rheumatology urban practice.
19575154 Infectious aspects and the etiopathogenesis of rheumatoid arthritis. 2010 Apr Infections are believed to contribute to the maturation of the immune system from the innate to the adaptive phases and therefore may take part in the induction of autoimmune conditions. In the current study, we present an extensive analysis conducted on sera samples of patients with rheumatoid arthritis in order to seek evidence of previous or coexisting infectious processes using the Bio-Rad BioPlex immunoassay analyzer. We detected higher rates of serological evidence of infections with Epstein-Barr virus and cytomegalovirus viruses. Our findings may indicate a role of these viruses in the pathogenesis of RA.
21061440 B7-H1 expression on non-B and non-T cells promotes distinct effects on T- and B-cell respo 2010 Nov The immune system has developed several regulatory mechanisms to maintain homeostasis of adaptive immune responses. T-cell programmed death (PD)-1 recognition of B7-H1 (PD-L1) expressed on APC and non-lymphoid tissue regulates T-cell activation. We show that B7-H1(-/-) mice exhibit exacerbated proteoglycan (PG)-induced arthritis and increased Th-1 CD4(+) T-cell responses. Unexpectedly, the PG-specific antibody response in B7-H1(-/-) mice was diminished. A reduction in the number of peanut agglutinin(+) GC coincided with a decrease in CD19(+) GL-7(+) CD95(+) GC B cells that was a result of increased caspase-induced apoptosis. The percent of CD38(+) CD138(+) emerging plasma cells was decreased. B7-H1(-/-) mice exhibited an increased frequency of CD4(+) PD-1(hi) CXCR5(hi) ICOS(hi) CD62L(lo) T follicular helper cells that displayed a hyperactive phenotype with increased expression of mRNA transcripts for Bcl6, IL-21, and the apoptosis-inducer molecule FasL. In cell transfer of B7-H1(-/-) cells into SCID mice, non-B and non-T cells were sufficient to normalize the antibody response, T-cell hyperactivity, and the development of PG-induced arthritis. These findings indicate that B7-H1 on non-B and non-T cells signals through PD-1 on T effector cells to prevent excessive activation and reduce autoimmune arthritis. Furthermore, these findings demonstrate a novel role for B7-H1 expression in promoting B-cell survival by regulating the activation of T follicular helper cell.
19581902 B-cell-directed therapies for autoimmune disease. 2009 Aug Approval of the anti-CD20 antibody rituximab for the treatment of moderate-to-severe rheumatoid arthritis in patients who fail to respond to anti-tumor-necrosis-factor agents has raised interest in B-cell-directed therapy for this disease. A number of direct and indirect modalities with distinct mechanisms of action are being investigated, including anti-CD20 and anti-CD22 therapies, and new approaches for blocking members of the tumor necrosis factor cytokine family including B cell activating factor (BAFF) and a proliferation ligand (APRIL), which are at late stages of clinical development. Clinical experience is most extensive with rituximab, and suggests that targeting 'autoimmune' memory B cells is a feasible approach for treating autoimmune disease. Although anti-CD20 therapy has only been approved for rheumatoid arthritis thus far, data suggest this approach could be valid for other autoimmune diseases, including systemic lupus erythematosus, Sjögren's syndrome, vasculitides, autoimmune cytopenias, and neurologic and dermatologic autoimmune diseases. Additional studies of direct and indirect B-cell-directed treatments are needed before we can draw conclusions as to the value of this approach in patients with various autoimmune diseases and whether more precisely defined techniques than these are required to target the complex humoral system effectively.
21042022 Efficacy and safety of the selective cyclooxygenase-2 inhibitor celecoxib in the treatment 2011 BACKGROUND/AIMS: Gastrointestinal (GI) disorders are common adverse reactions of nonsteroidal anti-inflammatory drugs (NSAIDs). Loxoprofen is a representative NSAID widely used in East Asia. A selective cyclooxygenase-2 inhibitor, celecoxib, was introduced in Japan in 2007. In this study, we aimed to compare the efficacy and safety of celecoxib with those of loxoprofen in Japanese patients. METHODS: We analyzed the data from 12 clinical studies conducted in Japan. These data of Japanese patients were compared with those of the patients in the West that had been published after 2000. RESULTS: The efficacy of celecoxib as an analgesic was comparable to that of loxoprofen, whereas serious GI events, including symptomatic ulcers, were significantly less frequent with celecoxib than with loxoprofen in Japanese patients with rheumatoid arthritis (RA) and osteoarthritis (OA) (p = 0.039). These results were consistent with the findings of the studies conducted in the West. The incidence of serious cardiovascular events was 0.1% in 2,398 subjects on celecoxib, which was not statistically different from the incidence in subjects on loxoprofen (0.3%; p = 0.3404) and those on placebo (0.2%); this result was also consistent with the data of the studies conducted in the West. CONCLUSION: The analgesic activity of celecoxib, which was used for the treatment of RA, OA, and low back pain, was comparable to that of loxoprofen, and celecoxib was safer in terms of GI injury often caused by other nonselective NSAIDs.
19582451 Routine patellar resurfacing using an inset patellar technique. 2010 Oct The management of the patella in total knee arthroplasty still causes controversy. Whether or not to resurface the patella in primary total knee arthroplasty remains unclear. In this study we examined 220 consecutive total knee replacements, by a single surgeon, where the patella was routinely resurfaced using the inset technique. All patellae were suitable for resurfacing. Patellar thickness was not altered in 54.5% of patellae. In 97.2% the patella was within 2 mm of the original thickness. There were no significant complications. In this study we have found that the inset technique of patella resurfacing in total knee replacement is a simple and safe resurfacing procedure.
19347280 Quantitative measurement of cytokine expression in synoviocytes derived from rheumatoid ar 2009 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by pain, swelling and progressive destruction of synovial joints. The synovial membranes of the affected joints markedly increase in size due to infiltration of several cell types, of which macrophages, lymphocytes and fibroblasts are most abundant. These cell types are activated and release a plethora of inflammatory mediators, such as cytokines, chem-okines and matrix metalloproteinases (MMPs). Synovial membranes can be removed from the joints of RA patients (most commonly when the respective joint is undergoing replacement therapy) and enzymati-cally digested, analyzed or cultured ex vivo. Analysing the cytokine profile of distinct populations of ex vivo RA-patients derived synoviocytes can provide an insight into the pathogenic mechanisms underlying RA. Additionally, since ex vivo cultures of synoviocytes spontaneously produce cytokines they serve as an excellent model for investigating the efficacy of novel anti-inflammatory drugs.
20633016 Pharmacological modulation by celecoxib of cachexia associated with experimental arthritis 2010 Nov BACKGROUND AND PURPOSE: Non-steroidal anti-inflammatory drugs improve inflammatory cachexia in several conditions. Thus, we have explored inhibition of cyclooxygenase-2 (COX-2) in an experimental model of rheumatoid cachexia in rabbits. EXPERIMENTAL APPROACH: Chronic arthritis was induced in immunized rabbits by repeated intra-articular injections of ovalbumin. To increase the degree of systemic inflammation and also to induce atherosclerotic lesions, the animals were fed a hyperlipidaemic diet (2% cholesterol and 6% peanut oil) and were given an endothelial injury of the femoral artery. Rabbits were randomized to receive the COX-2 inhibitor celecoxib (10 mg·kg⁻¹ ·day⁻¹) or no treatment. After 4 weeks, sera, peripheral mononuclear cells and vessel specimens were collected. KEY RESULTS: Inhibition of COX-2 by celecoxib modulated the systemic inflammatory response and increased total cholesterol and triglyceride levels. Celecoxib also minimized weight loss and prevented serum albumin fall. At a vascular level, celecoxib reduced COX-2 protein in the femoral arterial wall, but did not modify size or the macrophage infiltration of femoral lesions nor the percentage of rabbits with spontaneous aortic plaques. CONCLUSIONS AND IMPLICATIONS: Our animal model induced a severe inflammatory cachexia, comparable to that of persistently active rheumatoid arthritis. The inhibition of COX-2 by celecoxib improves this state, suggesting that COX products play an important role in its development, without affecting the development or the progression of vascular lesions. Overall, these results suggest that celecoxib might be considered as a new therapeutic tool for the treatment of rheumatoid cachexia.
20880053 Rheumatoid arthritis and salivary biomarkers of periodontal disease. 2010 Dec AIM: To test the hypothesis that rheumatoid arthritis (RA) influenced levels of salivary biomarkers of periodontal disease. METHODS: Medical assessments, periodontal examinations and pain ratings were obtained from 35 RA, 35 chronic periodontitis and 35 age- and gender-matched healthy controls in a cross-sectional, case-controlled study. Unstimulated whole saliva samples were analysed for interleukin-1β (IL-1β), matrix metalloproteinase-8 (MMP-8) and tumour necrosis factor-α (TNF-α) concentrations. RESULTS: The arthritis and healthy groups had significantly less oral disease than the periodontitis group (P<0.0001), with the arthritis group having significantly more sites bleeding on probing (BOP) than matched controls (P=0.012). Salivary levels of MMP-8 and IL-1β were significantly elevated in the periodontal disease group (P<0.002), and IL-1β was the only biomarker with significantly higher levels in the arthritis group compared with controls (P=0.002). Arthritis patients receiving anti-TNF-α antibody therapy had significantly lower IL-1β and TNF-α levels compared with arthritis patients not on anti-TNF-α therapy (P=0.016, 0.024) and healthy controls (P<0.001, P=0.011), respectively. CONCLUSION: RA patients have higher levels of periodontal inflammation than healthy controls, i.e., an increased BOP. Systemic inflammation appears to influence levels of select salivary biomarkers of periodontal disease, and anti-TNF-α antibody-based disease-modifying therapy significantly lowers salivary IL-1β and TNF-α levels in RA.
19779724 Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoi 2010 Jul Rheumatoid arthritis is a chronic autoimmune disorder associated with altered expression of pro- and anti-inflammatory cytokines in the affected tissues. The aim of this study was to investigate the association between promoter polymorphisms of TNFalpha and IL-10 gene with susceptibility, age of disease onset and disease severity in North Indian patients with rheumatoid arthritis (RA). SNPs at position -308 and -863 of TNF gene and -819/-592 and -1082 position of IL-10 gene were determined in 222 patients and 208 healthy controls using RFLP or ARMS method. Polymorphism TNF -308A was less prevalent among the patients (1.7%) than controls (4.9%; p = 0.01, OR: 0.32, 95% CI: 0.13-0.76). Among female patients, IL-10 -592A allele associated with higher baseline disease activity scores (5.77 +/- 1.99) than -592C (5.57 +/- 1.19; p = 0.04). Female patients carrying allele A of TNFalpha -863 had earlier age of onset of RA (33.99 +/- 9.6 years) than those with allele C (36.15 +/- 11.21 years; p = 0.043). In conclusion, allele A at TNFalpha -308 locus provides protection against RA in North Indian population while another TNF allele A at -863 position had weak association with earlier onset of disease in female patients. On the other hand promoter polymorphisms of IL-10 did not affect susceptibility but polymorphism at -819/-592A was associated with higher disease activity scores at baseline.
19473578 Correlation between atopy and hypersensitivity reactions during therapy with three differe 2009 Mar OBJECTIVE: The use of TNF-alpha antagon-ists (infliximab, etanercept, adalimumab) has changed the course of many rheumatic diseases including rheumatoid arthritis (RA). Since their approval, some questions regarding their safety have been raised. Both acute and delayed reactions have been described. METHODS: The aim of our work was to detect if there is a different incidence of hypersensitivity reactions - infusion reactions to infliximab or injection site reactions with etanercept or adalimumab - in atopic patients versus non- atopic patients. In 90 patients (82 females, 8 males) with rheumatoid arthritis we evaluated, during the first year of therapy with three different TNF-alpha blocking agents, total serum IgE (normal value <100 KU/L) (method ImmunoCAP PHADIA) and serum specific IgE performing a qualitative multi-allergen test for inhal-ant allergens (PHADIATOP, method ImmunoCAP PHADIA). In all patients we evaluated injection site reactions (ISR) to etanercept and adalimumab - erythema, edema and itching at the site of subcutaneous administration - and infusion reactions to infliximab - hypotension/hypertension, chest pain, dyspnea, laryngospasm, fever, urticaria angioedema. RESULTS: We obtained the following results: patients with high value of tot-al IgE were 15/90 (16.6 %), patients with total IgE in normal range were 75/90 (83.4.%), reactions in patients with high total IgE were 6.7% and in patients with normal total IgE were 18.7% (p=0.255 ns). As regards serum specific IgE, patients with specific IgE were 17/90 (18.8%) patients without specific IgE were 73/90 (81.2%), reactions in patients with specific IgE were 11.8% and in patients without specific IgE were 17.8% (p=0.547 ns). Also, when the data were divided for the three groups, the differences were not statistically significant. CONCLUSION: Adverse reactions to biological agents have been categorized into five types. In hypersensitivity reactions - the Beta type reactions - an immune mechanism is suspected. Our data showed that there was no correlation between the atopic status and the incidence of hypersensitivity reactions during the first year of therapy with three different TNF-alpha blocking agents.
19808132 An evidence-based assessment of the clinical significance of drug-drug interactions betwee 2009 Aug BACKGROUND: Clinically relevant drug-drug interactions (DDIs) must be recognized in a timely manner and managed appropriately to prevent adverse drug reactions or therapeutic failure. Because the evidence for most DDIs is based on case reports or poorly documented clinical information, there is a need for better assessment of their clinical relevance. OBJECTIVE: This study evaluates the interdisciplinary agreement between rheumatologists and clinical (hospital) pharmacists in assessing the clinical relevance of DDIs with disease-modifying antirheumatic drugs (DMARDs) and non-DMARD medications. METHODS: Potential DDIs were identified from the medical literature using MEDLINE and EMBASE for the years 1968-2009. The following search terms were used for the key word, title, and abstract sections of the publications: interaction(s), DMARD, disease-modifying antirheumatic drug(s), antirheumatic, rheumatology, rheumatoid arthritis, and the names of the individual DMARDs of interest (abatacept, adalimumab, anakinra, auranofin, aurothioglucose, aurothiomalate, d-penicillamine, etanercept, gold, [hydroxy]-chloroquine, interleukin-1 receptor antagonist, IL1-RA, infliximab, leflunomide, methotrexate, rituximab, and sulfasalazine/sulphasalazine). Reference lists of the retrieved publications were searched for further information on potential DDIs. All pharmacodynamic or pharmacokinetic DDIs between a DMARD and a non-DMARD identified were included in the study, with the exception of evidence regarding DMARD doses higher than used in the treatment of rheumatoid arthritis and interactions with phytotherapeutic or homeopathic preparations. Using a standard information set for each DDI (eg, from product labeling, textbooks, and the medical literature), a group of rheumatologists and a group of clinical pharmacists independently assessed whether the individual drug-DMARD combinations interacted and whether they required immediate intervention. Both groups consisted of 3 members (2 men and 1 woman), aged 40 to 60 years, who had >5 years of clinical experience and were currently involved in clinical practice in large, nonacademic teaching hospitals in the Netherlands. RESULTS: Forty potential DDIs with DMARDs were retrieved and assessed by the 2 groups. For 30 (75%) of these, rheumatologists and clinical pharmacists agreed about the requirement for immediate intervention. Specifically, 17 drug combinations (43%) were judged to interact and to require immediate intervention, and 13 combinations (33%) were judged either not to interact or to interact but not to require immediate intervention. For 10 combinations (25%), rheumatologists and clinical pharmacists were not in agreement. Overall, agreement between the groups was good (kappa = 0.80) for judging whether the drug combinations were interactions, and agreement was fair (kappa = 0.39) for judging whether immediate intervention was required. Prospective analysis of the data showed that rheumatologists tended to recommend immediate intervention more often when the adverse reaction to the DDI involved an increased risk of toxicity of the DMARD. In contrast, clinical pharmacists more often advocated immediate intervention when the adverse reaction involved decreased effectiveness of the DMARD. CONCLUSION: For a subset of DMARD-drug combinations, rheumatologists and clinical pharmacists differed in their assessments of clinical relevance.
19741054 Eicosapentaenoic acid attenuates arthritis-induced muscle wasting acting on atrogin-1 and 2009 Nov Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that has anti-inflammatory and anticachectic actions. The aim of this work was to elucidate whether EPA administration is able to prevent an arthritis-induced decrease in body weight and muscle wasting in rats. Arthritis was induced by intradermal injection of Freund's adjuvant; 3 days later, nine rats received 1 g/kg EPA or coconut oil daily. All rats were killed 15 days after adjuvant injection. EPA administration decreased the external signs of arthritis and paw volume as well as liver TNF-alpha mRNA. EPA did not modify arthritis-induced decrease in food intake or body weight gain. However, EPA treatment prevented arthritis-induced increase in muscle TNF-alpha and atrogin-1, whereas it attenuated the decrease in gastrocnemius weight and the increase in MuRF1 mRNA. Arthritis not only decreased myogenic regulatory factors but also increased PCNA, MyoD, and myogenin mRNA in the gastrocnemius. Western blot analysis showed that changes in protein content followed the pattern seen with mRNA. In the control rats, EPA administration increased PCNA and MyoD mRNA and protein. In arthritic rats, EPA did not modify the stimulatory effect of arthritis on these myogenic regulatory factors. The results suggest that in experimental arthritis, in addition to its anti-inflammatory effect, EPA treatment attenuates muscle wasting by decreasing atrogin-1 and MuRF1 gene expression and increasing the transcription factors that regulate myogenesis.
19023643 A1330V polymorphism of low-density lipoprotein receptor-related protein 5 gene and self-re 2009 We attempted to determine whether the A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 (LRP5) gene is associated with a risk of self-reported incident fractures and hypercholesterolemia in Japanese patients with rheumatoid arthritis (RA). DNA samples, laboratory data, and clinical data were obtained from 563 female RA patients who participated in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) observational cohort study. A1330V genotyping was performed using a custom TaqMan assay. Multiple logistic regression analyses showed that any incident fracture was significantly associated with older age (P = 0.000000036), high Japanese Health Assessment Questionnaire (J-HAQ) score (P = 0.016), and high daily prednisolone dose (P = 0.031), but not with the A1330V polymorphism, while serum total cholesterol levels >or=220 mg/100 mL were independently correlated with baseline older age (P = 0.00011), low J-HAQ score (P = 0.0098), high body mass index (P = 0.024), 1330VV genotype (P = 0.027), and high daily prednisolone dose (P = 0.031). Our results suggest that this LPR5 polymorphism does not appear to be a clinically useful marker for the prediction of fracture risk in Japanese female RA patients, although it is associated with increased serum total cholesterol levels.
19004043 Systemic lupus erythematosus features in rheumatoid arthritis and their effect on overall 2009 Jan OBJECTIVE: Features of systemic lupus erythematosus (SLE) are commonly observed in patients with rheumatoid arthritis (RA). However, their frequency and clinical significance are uncertain. We examined the frequency of SLE features in RA and their effect on overall mortality. METHODS: We assembled a population-based incidence cohort of subjects aged >or=18 years first diagnosed with RA [1987 American College of Rheumatology (ACR) criteria] between 1955 and 1995. Information regarding disease characteristics, therapy, comorbidities, and SLE features (1982 ACR criteria) were collected from the complete inpatient and outpatient medical records. Cox regression models were used to estimate the mortality risk associated with lupus features. RESULTS: The study population comprised 603 subjects with incident RA (mean age 58 yrs, 73% women) with a mean followup time of 15 years. By 25 years after RA incidence, >or=4 SLE features were observed in 15.5% of the subjects with RA. After adjustment for age and sex, occurrence of >or=4 SLE features was associated with increased overall mortality [hazard ratio (HR) 5.54, 95% confidence interval (CI) 3.59-8.53].With further adjustment for RA characteristics, therapy, and comorbidities, the association weakened but remained statistically significant (HR 2.56, 95% CI 1.60-4.08). After adjustment for age, sex, RA characteristics, therapy, and comorbidities, thrombocytopenia (2.0, 95% CI 1.2, 3.1) and proteinuria (1.8, 95% CI 1.3, 2.6) were significantly associated with mortality. CONCLUSION: SLE features were common in RA, given sufficient observation time. Subjects with RA who developed >or=4 SLE features had an increased risk of death. Proteinuria and thrombocytopenia were individually associated with an increased mortality risk.
20519185 [Role of Th17 cells in rheumatoid arthritis]. 2010 Jun 20 Th17 cells are the newly described subset of the CD4(+) T lymphocytes. Activated Th17 cells are characterized by their ability to produce IL-17A and other pro-inflammatory cytokines. IL-17A regulates immune function through its cell-surface receptor expressed on epithelial-and endothelial cells, fibroblasts and leukocytes by promoting neutrophil recruitment and releasing further pro-inflammatory mediators. Failures of the susceptible balance of the immunoregulation may lead to unchecked immune response and autoimmune diseases. The central role of Th17 cells and cytokines produced by Th17 cells were confirmed in a wide variety of human autoimmune diseases, including rheumatoid arthritis. Recently Th17 cells and its cytokines come into the focus of immunological research as potential therapeutic targets.