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ID PMID Title PublicationDate abstract
20018053 A genome-wide association scan for rheumatoid arthritis data by Hotelling's T2 tests. 2009 Dec 15 We performed a genome-wide association scan on the North American Rheumatoid Arthritis Consortium (NARAC) data using Hotelling's T2 tests, i.e., TH based on allele coding and TG based on genotype coding. The objective was to identify associations between single-nucleotide polymorphisms (SNPs) or markers and rheumatoid arthritis. In specific candidate gene regions, we evaluated the performance of Hotelling's T2 tests. Then Hotelling's T2 tests were used as a tool to identify new regions that contain SNPs showing strong associations with disease. As expected, the strongest association evidence was found in the region of the HLA-DRB1 locus on chromosome 6. In the region of the TRAF1-C5 genes, we identified two SNPs, rs2900180 and rs3761847, with the largest and the second largest TH and TG scores among all SNPs on chromosome 9. We also identified one SNP, rs2476601, in the region of the PTPN22 gene that had the largest TH score and the second largest TG score among all SNPs on chromosome 1. In addition, SNPs with the largest TH score on each chromosome were identified. These SNPs may be located in the regions of genes that have modest effects on rheumatoid arthritis. These regions deserve further investigation.
23675123 Relationship between NK Cell Activation and Clinical Response in Rheumatoid Arthritis Trea 2009 Jun INTRODUCTION: We investigated the relationship between the anti CD20 therapy and the NK cell phenotype in patients with Rheumatoid Arthritis (RA). METHODS: patients with seropositive RA according to the ACR criteria that was refractory to conventional and anti TNF alpha agents were studied. All patients were treated with Rituximab (1.0 g at days 1 and 15). At baseline and day 30 were collected: absolute counts of B cells (CD19+), total T cells (CD3+), helper (CD3+CD4+), cytotoxic (CD3+CD8+) and NK (CD16+CD56+). As NK activation marker was used CD54bright expression. Disease activity was primarily assessed using the the Clinical Disease Activity Index (CDAI); in addition, we calculated the Disease Activity Score 28-joint assessment (DAS28). RESULTS: 18 patients were enrolled (mean age ± SD 58.6 ± 2.8 years old). After the rituximab course, as expected CD19+ cells were not detectable, the cytotoxic lymphocytes and CD56+CD16+ cells downregulated (283 ± 34 and 85 ± 15 respectively), instead an up regulation of CD56+CD16+CD54bright was observed (187 ± 43). The dynamic of NK cells activation was significantly associated with clinical variables (r=0.811, p<0.001). CONCLUSIONS: our data suggest a role of rituximab therapy in varying NK phenotype in patients with RA and show that NK cells activation correlates with clinical response.
21124693 Pattern of Young and Old Onset Rheumatoid Arthritis (YORA and EORA) Among a Group of Egypt 2010 May 20 OBJECTIVE: Rheumatoid arthritis (RA) differs depending on the age of disease onset. The differences between EORA and YORA are important because they have clinical and therapeutic implications. METHOD: 1185 patients were ranked after classification according to age at onset of the disease into YORA I (16-40 years), YORA II (41-60 years) and EORA >60 years. All patients groups were compared, based on disease duration, disease activity, severity parameters and drug history. RESULTS: YORA I included 298 patients, 28.85% were males, with mean age of 29.4 ± 6 years and disease duration 4 ± 3.3 y, YORA II included 539 patients, 33.77% males, age 49.7 ± 6.1 y and disease duration 6.5 ± 5.6 y. EORA included 348 RA patients 40.5% males, age 67.1 ± 6.6 y, disease duration 9.95 ± 7.2 y. Activity was increased in EORA compared to YORA I and YORA II, while severity decreased in EORA. ESR, CRP and degree of anemia were higher in EORA. RF titer was higher in YORA. Small joints of the hands and feet were more involved in YORA, while, large joints in EORA. Rheumatoid nodules were increased in YORA I than EORA P = 0.04. Polymyalgia rheumatica was exclusively present in EORA group 25 patients 7.2%. Methotrexate was used in both YORA and EORA, with a higher mean of dosage in YORA than EORA. Multiple DMARDs in EORA was 57.9%, and biologics in 0.8% was which was significantly lower compared with YORA I, 86.3% and 1.7%, with P = 0.001. CONCLUSION: EORA has more active and less disabling and affects more males than YORA. The use of biologic therapy and combination DMARD therapy was less in EORA.
23105850 Effect of green tea extract and vitamin C on oxidant or antioxidant status of rheumatoid a 2009 Jul Elevated free radical generation in inflamed joints and impaired antioxidant system has been implicated in rheumatoid arthritis (RA). Green tea extracts (GTE) have been shown to reduce inflammation in inflammatory arthritis murine model. This study investigates possible mechanisms by which vitamin C and GTE protect joints in RA rat model. This study included forty adult male rats that were divided into four groups (10 rats each); control group, collagen II induced RA group (CII), CII treated with vitamin C (CII + Vit C) and CII treated with GTE (CII + GTE) in physiology laboratory, Assiut University, Egypt. After 45 days of treatment, plasma levels of lipid peroxides (LPO), nitric oxide (NO), ceruloplasmin (CP), superoxide dismutase (SOD), uric acid (UA) and glutathione (GSH) were detected using colorimetric methods, PGE(2) using ELISA and copper (Cu) and zinc (Zn) using spectrometer. In CII group, levels of LPO, NO, PGE(2), UA, CP, Cu were higher while SOD, GSH, Zn were lower than controls. In groups treated with vitamin C and GTE, levels of SOD, GSH were increased while levels of LPO, NO, PGE(2), Cu, CP were decreased compared with CII group. Levels of UA were decreased and Zn increased in GTE treated group compared with CII group. GTE treated group showed higher Zn and low Cu levels compared with vitamin C treated group. This study suggests proper GTE and vitamin C intake may effectively normalize the impaired oxidant/antioxidant system and delaying complication of RA.
20163888 Role of idiotype-anti-idiotype interactions in the induction of collagen-induced arthritis 2010 Dec The mechanism of autoantibodies (rheumatoid factor (RF) and anti-collagen autoantibodies) induction in collagen-induced arthritis (CIA) is unknown. The study assessed the hypothesis that activation of autoantibody-producing clones is mediated by idiotype-anti-idiotype (IAI) interactions with lymphocytes on heterologous collagen. It was demonstrated that RF-containing serum of rats immunized with bovine collagen (BCII) in ELISA competes with BCII for binding to anti-BCII antibodies. Immunization of rats with Fc fragments of IgG caused not only an increase in RF levels, but also induction of antibodies to BCII and anti-collagen autoantibodies. Taken together, these facts suggest that activation of RF-producing lymphocytes in CIA model occurs through IAI interactions with anti-BCII lymphocytes. Three populations of antibodies were detected in the blood of arthritic rats: a population of antibodies reacting only with BCII, a population of antibodies reacting only with rat collagen (RCII) and a population of antibodies that can bind to both bovine and rat collagen. It was shown that RF in relation to anti-collagen autoantibodies act as anti-idiotype antibodies, and a comparative analysis of antibody production in arthritic and resistant rats demonstrated that the level of anti-collagen autoantibody production depends on the level of RF production. This suggests that RF and RF-producing lymphocytes are involved in regulation of anti-collagen autoreactive lymphocyte activity through an IAI interaction mechanism. A direct activation of autoreactive anti-RCII lymphocytes by BCII cannot be excluded, but it can be supposed that induction of anti-collagen autoreactive lymphocytes needs a signal generated in IAI interactions by RF-producing lymphocytes. This hypothesis is based on the data obtained, and not only explains the mechanism of autoreactive lymphocytes activation in the rat CIA model, but also indicates that the key regulatory element in the development of arthritis in animals is RF-producing lymphocytes. The results allow a new insight on the role of RF in the pathogenesis of rheumatoid arthritis and on seeking more effective therapeutic means.
19217649 The interface of pain and mood disturbances in the rheumatic diseases. 2010 Aug OBJECTIVES: To review the overlap of pain and depression in the rheumatic diseases, focusing on fibromyalgia (FM) and rheumatoid arthritis, and to provide treatment recommendations based on an understanding of this interface. METHODS: A literature search was performed through PubMed and Medline, for the years 1978 to 2008 and using the keywords: depression, mood disorders, pain, arthritis, fibromyalgia, rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, scleroderma, antidepressants, exercise, and cognitive behavioral therapy. RESULTS: This review focuses on the pain/depression interface in common rheumatic disorders. FM is an excellent model to study the proposed mechanisms of such interactions. The potential genetic, inflammatory/immune, morphologic, and neurohormonal mechanisms that have been reported in FM are reviewed and compared with similar studies in depression. The importance of the interface of pain and depression has been noted in rheumatoid arthritis and other rheumatic illnesses, although there are very few studies to investigate their pathophysiologic underpinnings. General therapeutic recommendations can be made based on these overlapping models of the interface of pain and depression. CONCLUSIONS: Clinical and pathophysiologic studies in FM demonstrate the striking overlap of pain and depression. These studies pertain to a better understanding of the pain/depression interface in all chronic rheumatic illnesses.
19273306 Autoantibody to NA14 is an independent marker primarily for Sjogren's syndrome. 2009 Jan 1 Nuclear Autoantigen of 14 kDa (NA14) was originally identified using the serum of a Sjögren's syndrome (SS) patient as probe in screening a human testis cDNA expression library. To date there is no report in the systematic analysis of the prevalence of autoantibodies to NA14. In this study, anti-NA14 was determined in several rheumatic diseases from independent cohorts in the US and Japan. The prevalence of anti-NA14 were 18/132 (13.6%) in primary SS, 0/50 (0%) secondary SS, 2/100 (2%) SLE, 1/43 (2.3%) scleroderma, 0/54 (0%) rheumatoid arthritis, 1/29 (3.4%) polymyositis/dermatomyositis, and 0/58 (0%) normal healthy controls. The frequencies of anti-NA14 positive sera in primary SS are statistically greater than normal healthy controls (p=0.006), secondary SS (p=0.044), and other rheumatic diseases. Furthermore, among 11 anti-NA14 positive primary SS sera, 4/11 (36.3%) sera were negative for both anti-SS-A/Ro and SS-B/La antibodies. Thus anti-NA14 autoantibodies may be useful for the discrimination of primary versus secondary SS and serve as a diagnostic marker for primary SS especially in seronegative (anti-SS-A/Ro and anti-SS-B/La antibodies negative) patients with SS.
25126319 Effectiveness of anti-tumor necrosis factor agents in the treatment of rheumatoid arthriti 2010 Jul OBJECTIVE: The efficacy of anti-tumor necrosis factor therapies in rheumatoid arthritis has been demonstrated in randomized clinical trials. The purpose of the present study was to evaluate the effectiveness of these agents for the treatment of rheumatoid arthritis in a real-world setting. METHOD: This retrospective chart review included patients from 6 clinics in the United States. Eligibility criteria included age ≥18 years, diagnosis of rheumatoid arthritis, and having been initiated with anti-tumor necrosis factor therapy (ie, adalimumab, etanercept, or infliximab) between January 1, 2002, and November 30, 2004. Patients were assessed for up to 2 years after therapy initiation. Primary outcomes of interest were improvements in 4 effectiveness measures-joint pain, joint swelling, joint stiffness, and fatigue. A total of 496 patients met the study's inclusion criteria: 84 (16.9%) in the adalimumab group, 146 (29.4%) in the etanercept group, and 266 (53.6%) in the infliximab group. RESULTS: Improvement in 1 of the 4 effectiveness measures was documented in 36.8% (n = 25) who received adalimumab, in 47.7% (n = 62) of those who received etanercept, and in 48.7% (n = 115) of patients who received infliximab. The infliximab group was the only cohort to demonstrate significant improvements from baseline in joint pain, joint swelling, and joint stiffness. The adalimumab group had significant improvement in joint pain (P = .004). No significant change in fatigue scores was reached with any of these agents. CONCLUSION: In the real-world setting of patients with rheumatoid arthritis, anti-tumor necrosis factor therapy shows significant improvements in joint pain, joint swelling, and joint stiffness, although there are differences in effectiveness in the 4 measures among the 3 agents assessed in this study.
19300364 Sjögren's syndrome of the oral cavity. Review and update. 2009 Jul 1 Sjögren's syndrome is one of the most frequent autoimmune diseases. It is a chronic and systemic disorder predominantly found in women, and is characterized by the appearance of a lymphocytic inflammatory infiltrate, with dryness of the oral cavity and eyes, secondary to involvement of the salivary and lacrimal glands. The underlying causal mechanism involves a number of factors and has not been clearly established, though an autoimmune response is known to be triggered, with the accumulation of immune complexes in the gland acini that interfere with gland function. In the oral cavity, xerostomia or hyposialia is the most disabling manifestation for patients, and is accompanied by rapidly progressing caries, candidiasis and an important worsening of buccodental health. The most important complication is a 44-fold increase in the risk of developing non-Hodgkin lymphoma, compared with the general population. The treatment of Sjögren's syndrome is limited to symptomatic management, and involves the use of solutions to replace salivary secretion and afford a measure of hydration, cholinergic agents such as pilocarpine to stimulate the unaffected gland tissue and, recently, the administration of substances that act against surface antigens of the B lymphocytes, such as anti-CD20 and anti-CD22 antibodies. The present study provides an update on this disease, placing special emphasis on its odontologic implications.
21808665 Novel information on the non-neuronal cholinergic system in orthopedics provides new possi 2009 Jun 30 Anti-cholinergic agents are used in the treatment of several pathological conditions. Therapy regimens aimed at up-regulating cholinergic functions, such as treatment with acetylcholinesterase inhibitors, are also currently prescribed. It is now known that not only is there a neuronal cholinergic system but also a non-neuronal cholinergic system in various parts of the body. Therefore, interference with the effects of acetylcholine (ACh) brought about by the local production and release of ACh should also be considered. Locally produced ACh may have proliferative, angiogenic, wound-healing, and immunomodulatory functions. Interestingly, cholinergic stimulation may lead to anti-inflammatory effects. Within this review, new findings for the locomotor system of a more widespread non-neuronal cholinergic system than previously expected will be discussed in relation to possible new treatment strategies. The conditions discussed are painful and degenerative tendon disease (tendinopathy/tendinosis), rheumatoid arthritis, and osteoarthritis.
19661538 Magnetic resonance imaging of the hand in psoriatic arthritis. 2009 Aug Although magnetic resonance imaging (MRI) studies of psoriatic arthritis (PsA) are fewer than those of rheumatoid arthritis (RA), interest in this field is growing. The type and site of the lesions, rather than the mere severity of synovitis, can help differentiate PsA from other arthritides. Extracapsular enhancement and enthesitis are features emphasized as typical of PsA, but their relevance for the diagnosis is more quantitative than qualitative. Erosions in PsA are probably less frequent and progressive than in RA. Bone edema is unlikely to predict the appearance of erosions in patients with PsA. The Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) system has been adapted to peripheral PsA, but standardization is still in progress. Dactylitis is a relatively specific feature of PsA. Its pathogenic mechanisms have been investigated with MRI. MRI evaluation of PsA may facilitate diagnosis, evaluation of treatment effects, and understanding of associated mechanisms.
28080887 Arthritis specialists being 'under-used'. 2010 Mar 3 Specialist nurses can enhance treatment of patients with rheumatoid arthritis, according to an influential group of MPs.
21794613 [Legionella in a patient with rheumatoid arthritis receiving abatacept]. 2009 Sep Abatacept is a new drug available for refractory Rheumatoid Arthritis (RA), as other biologic therapies this drug is not free of potentially serious adverse events. We present a case of a 73 year-old patient treated with abatacept who suffered a Legionella pneumophila type 1 pneumoniae.
19561617 Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for mainta 2009 Jul Although there have been major advances in the treatment of rheumatoid arthritis with the advent of biological agents, the mechanisms that drive cytokine production and sustain disease chronicity remain unknown. Tenascin-C (encoded by Tnc) is an extracellular matrix glycoprotein specifically expressed at areas of inflammation and tissue damage in inflamed rheumatoid joints. Here we show that mice that do not express tenascin-C show rapid resolution of acute joint inflammation and are protected from erosive arthritis. Intra-articular injection of tenascin-C promotes joint inflammation in vivo in mice, and addition of exogenous tenascin-C induces cytokine synthesis in explant cultures from inflamed synovia of individuals with rheumatoid arthritis. Moreover, in human macrophages and fibroblasts from synovia of individuals with rheumatoid arthritis, tenascin-C induces synthesis of proinflammatory cytokines via activation of Toll-like receptor 4 (TLR4). Thus, we have identified tenascin-C as a novel endogenous activator of TLR4-mediated immunity that mediates persistent synovial inflammation and tissue destruction in arthritic joint disease.
21195061 Etiological role of cigarette smoking in rheumatoid arthritis: Nasal exposure to cigarette 2011 Jan 28 Cigarette smoking is a major environmental risk factor for rheumatoid arthritis (RA). However, the experimental bases supporting the etiological role of cigarette smoking in RA have not been fully provided. We have reported that cigarette smoke condensate (CSC), by means of subcutaneous injection into DBA/1J mice with collagen and complete Freund's adjuvant or intraperitoneal injection one day before immunization, augmented the development of arthritis in the mouse model of collagen type II-induced arthritis (CIA). However, these experimental procedures may not be appropriate for cigarette smoking. In this study, we nasally exposed mice to mainstream CSC and found that CSC augmented the induction and development of arthritis and antibody level against collagen. Histological examination confirmed the augmenting effect of CSC. These findings provide experimental bases supporting the etiological role of cigarette smoking in RA.
19583652 Disability and pain management methods of Taiwanese arthritic older patients. 2009 Aug AIM: This study aims to investigate the prevalence of disability, factors influencing disability and pain self-management techniques employed by older arthritis patients in Taiwan. BACKGROUND: Arthritis is the most common chronic disease in older people. It may result in pain, stiffness and joint deformity, which ultimately lead to disability. Understanding the factors influencing disability is needed to help arthritis sufferers to achieve optimal health status. DESIGN: A cross-sectional design was employed for this study. METHODS: One hundred and fifty-one older persons diagnosed with either rheumatoid arthritis or osteoarthritis were interviewed in the rheumatology clinics located in two medical centres in northern Taiwan. Six questionnaires were administered: Barthel Index, Instrumental Activity of Daily Living, Rapid Assessment of Disease Activity in Rheumatology, the Chinese version of Pain Management Inventory, Geriatric Depression Scale and Life Satisfaction Index. RESULTS: Disability was found in 11% of Taiwanese individuals diagnosed with either rheumatoid arthritis or osteoarthritis. Those in disability reported more severe disease activity, pain, depression and lower life satisfaction. Hierarchical multiple regression analysis revealed that 31-46% of the total variance of disability could be explained by age, gender, marriage, joint pain score, diagnosis, disease activity, depression and pain management. Patients with rheumatoid arthritis had significantly higher levels of disability, disease activity during the preceding six months, more depression and less life satisfaction than patients with osteoarthritis. CONCLUSION: Higher disability was explained by older age, female, unmarried, diagnosed with rheumatoid arthritis, more joint pain, more disease severity, more depression and more use of pain management strategies in arthritis patients. RELEVANCE TO CLINICAL PRACTICE: Nurses are urged to recognise the individual differences among the factors that are thought to contribute most to disability. An individualised, multidimensional and comprehensive treatment plan with informational support is essential to maximise pain management skills of arthritic older people to achieve improvement in pain, level of disability and mental health.
19124739 Plasmacytoid dendritic cells regulate breach of self-tolerance in autoimmune arthritis. 2009 Jan 15 Achieving remission in rheumatoid arthritis (RA) remains elusive despite current biological therapeutics. Consequently, interest has increased in strategies to re-establish immune tolerance to provide long-term disease suppression. Although dendritic cells (DC) are prime candidates in initiating autoreactive T cell responses, and their presence within the synovial environment suggests a role in generation and maintenance of autoreactive, synovial T cell responses, their functional importance remains unclear. We investigated the contribution made by plasmacytoid DCs (pDCs) in the spontaneous breach of tolerance to arthritis-related self proteins, including rheumatoid factor, citrullinated peptide, and type II collagen observed in a novel arthritis model. Selective pDC depletion in vivo enhanced the severity of articular pathology and enhanced T and B cell autoimmune responses against type II collagen. pDC may offer a net anti-inflammatory function in the context of articular breach of tolerance. Such data will be vital in informing DC modulatory/therapeutic approaches.
27789980 Intra-articular corticosteroids in the treatment of juvenile idiopathic arthritis: Safety, 2009 Intra-articular corticosteroid injection (IACI) has been used in the treatment of inflammatory arthritis in adults for over fifty years. Over the last two decades, IACI has become an important tool in the management of juvenile idiopathic arthritis (JIA), particularly in the oligoarthritis subset of JIA. Many factors may affect the efficacy of this treatment modality, although the majority of evidence on this topic is anecdotal, nonconvincing, or conflicting. The review examines the rationale, efficacy, safety, and application of the use of IACI in the treatment of JIA, focusing on factors that affect the outcome following IACI.
20018007 A quantile-based method for association mapping of quantitative phenotypes: an application 2009 Dec 15 Genetic association of population-based quantitative trait data has traditionally been analyzed using analysis of variance (ANOVA). However, violations of certain statistical assumptions may lead to false-positive association results. In this study, we have explored model-free alternatives to ANOVA using correlations between allele frequencies in the different quantile intervals of the quantitative trait and the quantile values. We performed genome-wide association scans on anti-cyclic citrullinated peptide and rheumatoid factor-immunoglobulin M, two quantitative traits correlated with rheumatoid arthritis, using the data provided in Genetic Analysis Workshop 16. Both the quantitative traits exhibited significant evidence of association on Chromosome 6, although not in the human leukocyte antigen region which is known to harbor a major gene predisposing to rheumatoid arthritis. We found that while a majority of the significant findings using the asymptotic thresholds of ANOVA was not validated using permutations, a relatively higher proportion of the significant findings using the asymptotic cut-offs of the correlation statistic were validated using permutations.
20444271 The likelihood of persistent arthritis increases with the level of anti-citrullinated pept 2010 INTRODUCTION: We wanted to assess the importance of the levels of anti-citrullinated peptide antibody (anti-CCP) and immunoglobulin M (IgM) rheumatoid factor (RF) in predicting development of persistent arthritis from undifferentiated arthritis (UA), and to investigate whether there is an added predictive value for persistent arthritis in testing for both anti-CCP and IgM RF. METHODS: Patients with UA (exclusion of definite non-rheumatoid arthritis (RA) diagnoses) included in the Norwegian very early arthritis clinic were assessed for development of persistent arthritic disease. The effect of antibody level on the likelihood of persistent arthritis was investigated, and the sensitivity and specificity for persistent arthritis for anti-CCP and IgM RF, separately and combined, was determined. RESULTS: A total of 376 UA patients were included (median arthritis duration 32 days). 59 (15.7%) patients were IgM RF positive, and 62 (16.5%) anti-CCP positive. One hundred, seventy-four (46.3%) had persistent disease after one year. Overlap of anti-CCP and IgM RF positivity was 58%. Sensitivity/specificity for persistent arthritis was 28/95% for IgM RF alone, 30/95% for anti-CCP alone, and 37/92% for positivity of both anti-CCP and IgM RF. The likelihood for persistent disease increased with increasing levels of both anti-CCP and IgM RF. CONCLUSIONS: The likelihood of developing persistent arthritis in UA patients increases with the level of anti-CCP and IgM RF. Testing both anti-CCP and IgM RF has added predictive value in UA patients. This study suggests that antibody level should be taken into account when making risk assessments in patients with UA.