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

ID PMID Title PublicationDate abstract
23180817 An HLA-DRB1-coded signal transduction ligand facilitates inflammatory arthritis: a new mec 2013 Jan 1 Particular alleles of HLA contribute to disease susceptibility and severity in many autoimmune conditions, but the mechanisms underlying these associations are often unknown. In this study, we demonstrate that the shared epitope (SE), an HLA-DRB1-coded sequence motif that is the single most significant genetic risk factor for erosive rheumatoid arthritis, acts as a signal transduction ligand that potently activates osteoclastogenesis, both in vitro and in vivo. The SE enhanced the production of several pro-osteoclastogenic factors and facilitated osteoclast (OC) differentiation in mouse and human cells in vitro. Transgenic mice expressing a human HLA-DRB1 allele that code the SE motif demonstrated markedly higher propensity for osteoclastogenesis and enhanced bone degradation capacity ex vivo. In addition, the SE enhanced the differentiation of Th17 cells expressing the receptor activator for NF-κB ligand. When the two agents were combined, IL-17 and the SE enhanced OC differentiation synergistically. When administered in vivo to mice with collagen-induced arthritis, the SE ligand significantly increased arthritis severity, synovial tissue OC abundance, and bone erosion. Thus, the SE contributes to arthritis severity by activating an OC-mediated bone-destructive pathway. These findings suggest that besides determining the target specificity of autoimmune responses, HLA molecules may influence disease outcomes by shaping the pathogenic consequences of such responses.
21640051 Obesity, adipose tissue and rheumatoid arthritis: coincidence or more complex relationship 2011 Jul In the last two decades we have witnessed a boost in scientific interest and knowledge of adipose tissue biology to such an extent that it was promoted to an active endocrine organ. Adipose tissue is not just related to body weight and appetite regulation. It is also implicated in obesity, a low-grade inflammatory state, as well as inflammatory conditions including rheumatoid arthritis (RA), an autoimmune disease where anti- and pro-inflammatory cytokine balance is critical. All major adipose derived products, simply termed adipokines, like leptin, adiponectin, visfatin and resistin, reportedly participate in inflammation and immunity. In this review we explore in depth the relationship between adipose tissue and RA, with focus on possible mechanisms, beyond observations about circulating or synovial levels, and special reference to future perspectives and clinical implications.
21551505 In patients with early inflammatory polyarthritis, ACPA positivity, younger age and ineffi 2011 Aug OBJECTIVES: To identify baseline disease-related predictors in patients with early inflammatory polyarthritis (IP) for starting subsequent biological therapy and to determine if patients who failed their first non-biological disease-modifying antirheumatic drug (DMARD) within 6 months were more likely to need biological therapy. METHODS: Patients with early IP recruited between 1990 and 1994 (cohort 1) and between 2000 and 2004 (cohort 2) in the Norfolk Arthritis Register were included in this study. The association between possible predictors with the start of biological therapy was assessed using Cox proportional hazards regression models. RESULTS: 32/407 (7.9%) patients in cohort 1 and 45/416 (10.8%) patients in cohort 2 received biological therapy during follow-up. In both cohorts, anti-citrullinated protein antibody (ACPA) positivity (cohort 1, HR 7.62, 95% CI 2.46 to 23.58; cohort 2, HR 4.68, 95% CI 2.23 to 9.78) was the strongest predictor for starting biological therapy. In cohort 2, younger patients (HR 0.97, 95% CI 0.95 to 0.99) and patients who failed their first non-biological DMARD within 6 months due to inefficacy were also more likely to receive biological therapy (HR 2.35, 95% CI 1.05 to 5.27). CONCLUSION: Patients with early IP who are ACPA positive, are younger or who fail their first non-biological DMARD due to inefficacy within 6 months are more likely to need biological therapy.
21822042 [Recommendations for the prevention and management of tuberculosis in patients treated wit 2011 Patients receiving tumor necrosis factor alpha inhibitors for the treatment of rheumatic diseases (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis) are at high risk of developing tuberculosis during treatment. This article gives the recommendations for the prevention and management of tuberculosis in patients with rheumatic diseases before initiating therapy with tumor necrosis factor alpha inhibitors. They are adapted considering the high prevalence of tuberculosis, high drug resistance of Mycobacterium tuberculosis, and extensive bacille Calmette-Guérin vaccination against tuberculosis in Lithuania. In order to reduce the risk of tuberculosis, the screening should be done before starting antitumor necrosis factor alpha therapy. This includes complete medical history and posterior-anterior, lateral chest radiography. Tuberculin skin test using the Mantoux method with 5 tuberculin units and interferon-gamma release assay should be performed in patients without posttuberculous radiological lesions. If Ghon's complex or untreated posttuberculous lesions are present, or if the results the Mantoux test or interferon-gamma release assay are positive, the patient should be treated for latent tuberculosis. For the treatment of latent tuberculosis, isoniazid and rifampicin are given for 3 months, and the introduction of antitumor necrosis factor alpha therapy is delayed at least for one month. In cases of suspected active Mycobacterium tuberculosis infection, tuberculosis should be confirmed microbiologically or morphologically, and adequate antituberculosis treatment should be initiated.
22191990 Pain and daily activities in rheumatoid arthritis. 2012 AIM: The aim of this study was to describe experiences of pain and its relationship to daily activities in people with rheumatoid arthritis (RA). METHOD: Seven semi-structured focus group discussions were conducted with 33 men and women of different ages with RA. Data were analysed with content analysis. RESULTS: Pain affected everyday life and may be a barrier to perform valued activities. Regarding the impact of pain on participation and independence, personal factors and the social environment were found to be important. It could be a struggle to find the right activity balance, since it was easy to be overactive, triggering subsequent elevation of pain levels. However, the participants also described activities as a mediator of pain and a distraction from it. CONCLUSION: The relationship between pain and daily activities in RA was complex. Pain as an impairment was expressed to be related to activity limitations and participation restrictions, as well as to contextual factors. These findings highlight the clinical importance of paying attention to the complexity of pain and its relation to daily activities and participation.
21881988 Injection-site reactions upon Kineret (anakinra) administration: experiences and explanati 2012 Feb Anakinra (Kineret), a recombinant form of human interleukin-1 (IL-1) receptor antagonist, is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate. Kineret is self-administered by daily subcutaneous injections in patients with active RA. The mechanism of action of anakinra is to competitively inhibit the local inflammatory effects of IL-1. Kineret is generally safe and well tolerated and the only major treatment-related side effects that appear are skin reactions at the injection site. Due to the relatively short half-life of anakinra, daily injection of the drug is required. This, in combination with the comparably high rates of injection-site reactions (ISRs) associated with the drug, can become a problem for the patient. The present review summarises published data concerning ISRs associated with Kineret and provides some explanations as to their cause. The objective is also to present some clinical experiences of how the ISRs can be managed.
22354566 Polymorphisms in the CTLA-4 gene and rheumatoid arthritis susceptibility: a meta-analysis. 2012 Jun INTRODUCTION: The +49A/G polymorphism and CT60 polymorphism in the CTLA-4 gene have been extensively examined for the association with rheumatoid arthritis (RA); however, results of different studies have been inconclusive. The aim of this study is to comprehensively evaluate the genetic risks of +49A/G and CT60 polymorphisms in the CTLA-4 gene for RA. METHODS: A meta-analysis was carried out to analyze the association of +49A/G and CT60 polymorphisms with RA risk. RESULTS: A total of 30 case-control studies in 20 articles were included in this meta-analysis. The results indicated that the variant G allele carriers (GG + GA) of +49A/G polymorphism had an 18% increased risk of RA when compared with the homozygote AA (odds ratio (OR) = 1.18, 95% confidence interval (CI): 1.04-1.34 for GG + AG vs. AA). In addition, the variant CT60 A allele carriers of CT60 polymorphism had a 14% decreased risk of RA when compared with the homozygote GG (OR = 0.86, 95%CI = 0.78-0.95 for AA + AG vs. GG). In the subgroup analysis by ethnicity, significant elevated RA risks were associated with +49G allele carriers in Asians, but not in Europeans. However, for CT60 polymorphism, significant decreased RA risks were associated with CT60 A allele carriers in Europeans, but not in Asians. CONCLUSIONS: This meta-analysis suggested that the +49A/G and CT60 polymorphisms in the CTLA-4 gene may be risk factors for RA.
21120498 The treatment of rheumatoid arthritis during pregnancy. 2011 Apr There are a wide variety of medications available to treat patients with rheumatoid arthritis, many of which are considered unsafe during pregnancy. It is important to tailor a treatment regimen that stabilises the woman's disease prior to conception, using medications that are safe to continue throughout pregnancy and the post-partum period. Drugs that may be safely used during pregnancy include NSAIDs, corticosteroids, plus several DMARDs, including sulfasalazine and hydroxychloroquine. Drugs recommended to be stopped before pregnancy include methotrexate and leflunomide, plus the biologics: anti-TNF agents, rituximab and abatacept.
21246364 Comparison of serological markers between ACPA⁺ and ACPA⁻ of RA patients. 2012 May Anti-citrullinated protein/peptide antibodies (ACPA) have recently emerged as sensitive and specific serological markers of rheumatoid arthritis (RA), providing superior alternative of the rheumatoid factor (RF) test in the laboratory diagnostics of RA. We compare the change of serum RF, CRP, IgG, IgM, IgA, total complement, C3 and C4. The sera sample was collected from 123 patients with RA. ACPA were detected with ELISA, and RF, CRP and total complement (Ct), C3 and C4 were examined by automatic biochemical analyzer. Serum RF and total complement concentrations were significantly higher in ACPA+ than in ACPA-, but there were no correlation between ACPA and RF and Ct. Between ACPA+ and ACPA-, there were no significant difference of CRP, IgG, IgM, IgA, total complement, C3 and C4. While there were significant correlation between the concentration of C3 and IgM and ACPA in ACPA+. CONCLUSION: This is the first study to show that ACPA concentration in ACPA+ patients with RA is positively related to serum IgM and C3 levels.
23264359 Treatment to lipid targets in patients with inflammatory joint diseases in a preventive ca 2013 Dec OBJECTIVES: To perform cardiovascular risk stratification in patients with inflammatory joint diseases (IJD) and treat to lipid targets according to recommendations. METHODS: We initiated a preventive cardio-rheuma clinic based on the unmet need of adequate cardiovascular prevention in IJD patients. A full cardiovascular risk stratification was performed at the first consultation (history of conventional risk factors and of cardiovascular disease, lipid measurement, blood pressure and ultrasound examination of both carotid arteries), and the patient was classified to either a primary or secondary cardiovascular prevention regime, or to have a low risk (no intervention). Lipid-lowering treatment was adjusted until at least two lipid targets were achieved. RESULTS: Of the 426 patients referred, 36.6% had a systematic coronary risk evaluation less than 5% (no lipid-lowering intervention). The remaining 270 patients ((rheumatoid arthritis (RA), n=165; ankylosing spondylitis (AS), n=70; and psoriatic arthritis (PsA), n=35) were assigned to either primary (n=63) or secondary prevention (n=207). There were significant differences between the patient groups regarding age (p<0.001), sex (p<0.001) and disease duration (p<0.001). Lipid changes in IJD patients were: total cholesterol -1.86±1.20 mmol/l (p<0.001); low-density lipoprotein cholesterol -1.74±1.11 (p<0.001); high-density lipoprotein cholesterol 0.01±0.30 (p=0.61); triglycerides -0.28±0.72 (p<0.001). The proportions of patients reaching at least two lipid targets were for RA 92.1%, AS 90.0% and PsA 82.9%. No serious adverse events were observed. CONCLUSIONS: There was indication for cardiovascular prevention in a high proportion of IJD patients referred for cardiovascular risk stratification. Treatment to lipid targets was successful in approximately 90% of patients with IJD.
20817615 Peak and end effects in patients' daily recall of pain and fatigue: a within-subjects ana 2011 Feb Clinical research often relies on retrospective recall of symptom levels, but the information contained in these ratings is not well understood. The "peak-and-end rule" suggests that the most intense (peak) and final (end) moments of an experience disproportionately influence retrospective judgments, which may bias self-reports of somatic symptoms. This study examined the extent to which peak and end symptom levels systematically affect patients' day-to-day recall of pain and fatigue. Rheumatology patients (N = 97) completed 5 to 6 momentary ratings of pain and fatigue per day as well as a daily recall rating of these symptoms for 28 consecutive days. For pain, peak and end momentary ratings predicted daily recall of average pain beyond the actual average of momentary ratings. This effect was small, yet was confirmed in both between-person and within-person (repeated measures) analyses. For fatigue, neither peak nor end momentary symptoms significantly contributed to daily recall. Of note, the evidence for peak- and end-effects in recall of pain and fatigue varied significantly between individual patients. These findings suggest that peak- and end-effects create a small bias in recall reports of pain, but not fatigue. However, there are considerable individual differences in susceptibility to peak and end heuristics. PERSPECTIVE: The peak-end cognitive heuristic could bias end-of-day recall of pain and fatigue. An effect was shown for pain, but not for fatigue. The effects were small and were unlikely to substantially bias end-of-day assessments. Individuals were shown to differ in the degree that the heuristic was associated with recall.
20977385 Making the rheumatologist aware of patients' non-adherence does not improve medication adh 2011 May OBJECTIVES: We have developed an instrument that provides the physician structured information about medication use and patients' (non-)adherence. This study aimed to determine the effectiveness of this instrument on adherence and medication beliefs in outpatients with rheumatoid arthritis (RA). METHODS: In this within-subject controlled prospective cohort study, 50 outpatients were assessed during three consecutive visits to their rheumatologist. At these three points in time, patients' adherence, medication beliefs, satisfaction about information about medication, and physical functioning were measured using validated self-report questionnaires. An intervention was scheduled during the second visit. The intervention consisted of a written report informing the physician about medication use and adherence to medication for each patient. The effectiveness of the intervention was evaluated by comparing outcome measures at the third visit to the same measures assessed prior to the intervention. RESULTS: At baseline, 30% of the patients (n = 50) were non-adherent. No significant changes in adherence were found between the first and second visit prior to the intervention. Adherence did not change after the intervention, compared to both of the adherence assessments prior to the intervention. Beliefs about medication, patients' satisfaction about information on medication, and physical functioning were also not significantly altered. CONCLUSION: Supplying the rheumatologist a report with information about medication use and adherence did not change adherence or patients' beliefs about medication. Further research is necessary to ensure effective support for adherence for individual patients with RA.
21068091 The need for personalised medicine for rheumatoid arthritis. 2011 Jan An expanding range of biological therapies is available for patients with rheumatoid arthritis. Clinical trials and real-life experience demonstrate significant interpatient heterogeneity in efficacy as well as important adverse effects of these treatments. In order to maximise their benefit:risk ratios and to minimise later joint damage, we need to define predictors of response and, ideally, of adverse effects for each of these drugs. There is huge interest in this field of 'personalised medicine', which should allow us to optimally match patient with treatment, providing the parallel benefit of reduced treatment costs. In this short article the current state of the art for licensed biological therapies is summarised. There have been some noteworthy discoveries but the challenge is now to design studies to confirm and validate these findings while also devising large, potentially international, collaborations to identify additional, robust biomarkers that predict outcome.
22942262 Anti-DFS70/LEDGF antibodies are more prevalent in healthy individuals compared to patients 2012 Nov OBJECTIVE: Antinuclear antibodies (ANA) are a serological hallmark of systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE). While a number of ANA patterns detected by indirect immunofluorescence (IIF) have diagnostic significance, autoantibodies producing the dense fine speckled (DFS) pattern have been reported to be more prevalent in healthy individuals than in SARD. METHODS: Sequential samples submitted for ANA testing were screened for anti-DFS antibodies by IIF (n = 3263). Samples with the DFS pattern were tested for anti-DFS70/lens epithelium-derived growth factor (LEDGF) antibodies by ELISA and by a novel chemiluminescence assay (CIA, Quanta Flash DFS70). Sera from patients with various diseases and healthy individuals were tested for anti-DFS70/LEDGF antibodies by CIA. A cohort of 251 patients with SLE was used to analyze serological and clinical associations of anti-DFS70 antibodies. RESULTS: The frequency of anti-DFS antibodies by IIF was 1.62%. The prevalence of anti-DFS70/LEDGF antibodies as detected by CIA in the different cohorts was 8.9% in healthy individuals, 2.8% in SLE, 2.6% in rheumatoid arthritis, 4.0% in asthma, 5.0% in interstitial cystitis, 1.7% in Graves' disease, and 6.0% in Hashimoto's thyroiditis. Of note, the prevalence of anti-DFS70/LEDGF antibodies was significantly higher in healthy individuals compared to patients with SARD (p = 0.00085). In SLE results, anti-DFS70/LEDGF antibodies were not significantly associated with clinical features or other autoantibodies typically found in SLE. Only 1/7 SLE sera showed anti-DFS70/LEDGF, but no other autoantibody reactivity. CONCLUSION: "Monospecific" anti-DFS70/LEDGF antibodies may represent a biomarker for differentiating SARD from non-SARD individuals, but there is a need for a reliable assay to ensure reactivity to DFS70.
22018182 Prednisone chronotherapy. 2011 Sep Glucocorticoids (GCs) are widely used in clinical medicine because of their anti-inflammatory and immunosuppressive effects. However, these agents have a considerable potential for adverse effects, especially if used in high doses. The currently most advanced approach to improve the risk-benefit ratio of GCs is low-dose prednisone chronotherapy with modified release (MR) prednisone timing drug release to chronobiological rhythms. In RA, the circadian rhythms of pain, stiffness and functional disability show maximum symptoms in the early morning hours, which is preceded by elevated levels of pro-inflammatory cytokines, in particular interleukin 6. It was hypothesised that preventing the nocturnal rise of pro-inflammatory cytokines by GC therapy is more effective than treating established symptoms in the morning. As waking in the night for tablet intake is impracticable, modified release (MR) prednisone was developed, which releases prednisone approximately four hours after ingestion (i.e. at approximately 2 am if taken at 10 pm bedtime). Data from two large-scale trials in rheumatoid arthritis (RA) (CAPRA-1 and 2) document that MR prednisone has greater efficacy for long-term, low-dose glucocorticoid treatment in patients with RA, with a significant reduction in morning joint stiffness, in addition to all known therapeutic effects with conventional prednisone and a similar safety profile without additional suppression of hypothalamic-pituitary-adrenal (HPA) axis. For patients with RA on low to medium doses of prednisone, especially those who continue to experience a long duration of morning stiffness, MR prednisone appears a valuable additional treatment option.
23387276 [Characteristics of Ca2+, Mg(2+)-ATPases of peripheral blood lymphocytes of patients with 2012 Nov The analysis of the kinetic properties of Ca2+, Mg(2+)-ATPase of saponin-perforated peripheral blood lymphocytes of donors and patients with rheumatoid arthritis and ankylosing spondylitis was carried out. When analyzing the alterations in hydrolase activity of Ca2+, Mg(2+)-ATPase it was shown that affinity of Ca2+, Mg(2+)-ATPase of plasma membrane and membranes of endoplasmic reticulum for ATP do not significantly differ. It was found that the inhibition of examined enzyme systems occurs by mixed type both due to the reduction of maximum reaction rate and to the decrease of Ca2+, Mg(2+)-ATPase affinity for ATP in conditions of rheumatic pathology in the immunocompetent cells. It was identified that Ca2+, Mg(2+)-ATPase had significantly lower affinity for Ca2+ in lymphocytes of persons with rheumatic disorders than in donors.
22800875 Vitamin D, metabolic dyslipidemia, and metabolic syndrome in rheumatoid arthritis. 2012 Oct PURPOSE: Vitamin D deficiency is a potential risk factor for cardiometabolic disease. We investigated the associations between vitamin D and dyslipidemia and the metabolic syndrome in patients with rheumatoid arthritis, a group at high risk for cardiovascular disease. METHODS: Serum 25(OH)vitamin D and lipoprotein levels were measured at baseline in a random sample of 499 participants, ages 18-85 years, enrolled in a randomized trial of golimumab (GOlimumab Before Employing methotrexate as the First-line Option in the treatment of Rheumatoid arthritis of Early onset or GO-BEFORE Trial). Participants had rheumatoid arthritis with active disease, and were naïve to methotrexate and biologic therapies. Multivariable linear regression was performed to assess associations between vitamin D levels and lipoprotein fractions. Multivariable logistic regression was performed to determine the odds of hyperlipidemia and the metabolic syndrome in participants with vitamin D deficiency (<20 ng/mL). RESULTS: In multivariable linear regression, vitamin D levels (per 10 ng/mL) were associated inversely with low-density lipoprotein (β: -0.029 [-0.049, -0.0091], P=.004) and triglyceride (β: -0.094 [-0.15, -0.039] P=.001) levels, adjusted for demographic, cardiovascular, and disease-specific variables. Vitamin D and high-density lipoprotein levels were not associated in univariate or multivariate analyses. Vitamin D deficiency was associated independently with an increased odds of hyperlipidemia (odds ratio 1.72; 95% confidence interval, 1.10-2.45; P=.014) and metabolic syndrome (odds ratio 3.45; 95% confidence interval, 1.75-6.80; P <.001) in adjusted models. CONCLUSIONS: In conclusion, vitamin D deficiency was associated with the metabolic syndrome and dyslipidemia in rheumatoid arthritis, suggesting a potential role in cardiovascular disease risk. Large-scale, prospective studies are needed to determine if vitamin D supplementation improves lipoprotein levels and reduces cardiovascular risk in rheumatoid arthritis.
21590684 The transcription factor FBI-1/OCZF/LRF is expressed in osteoclasts and regulates RANKL-in 2011 Sep OBJECTIVE: Since transcription factors expressed in osteoclasts are possible targets for regulation of bone destruction in bone disorders, we investigated the expression of the transcription factor FBI-1/OCZF/LRF (in humans, factor that binds to inducer of short transcripts of human immunodeficiency virus type 1; in rats, osteoclast-derived zinc finger; in mice, leukemia/lymphoma-related factor) in patients with rheumatoid arthritis (RA), and assessed its role in osteoclastogenesis in vivo. METHODS: Expression of FBI-1/OCZF was investigated in subchondral osteoclasts in human RA and in rat adjuvant-induced arthritis (AIA) using immunostaining and in situ hybridization, respectively. Transgenic mice overexpressing OCZF (OCZF-Tg) under the control of the cathepsin K promoter were generated, and bone mineral density and bone histomorphometric features were determined by peripheral quantitative computed tomography, calcein double-labeling, and specific staining for osteoclasts and osteoblasts. LRF/OCZF expression and the consequence of LRF inhibition were assessed in vitro with RANKL-induced osteoclast differentiation. RESULTS: FBI-1/OCZF was detected in the nuclei of osteoclasts in rat AIA and human RA. RANKL increased the levels of LRF messenger RNA and nuclear-localized LRF protein in primary macrophages. In OCZF-Tg mice, bone volume was significantly decreased, the number of osteoclasts, but not osteoblasts, was increased in long bones, and osteoclast survival was promoted. Conversely, inhibition of LRF expression suppressed the formation of osteoclasts from macrophages in vitro. CONCLUSION: FBI-1/OCZF/LRF regulates osteoclast formation and apoptosis in vivo, and may become a useful marker and target in treating disorders leading to reduced bone density, including chronic arthritis.
22563031 Immunomodulatory role of proteinase-activated receptor-2. 2012 Sep OBJECTIVE: Proteinase-activated receptor-2 (PAR(2)) has been implicated in inflammatory articular pathology. Using the collagen-induced arthritis model (CIA) the authors have explored the capacity of PAR(2) to regulate adaptive immune pathways that could promote autoimmune mediated articular damage. METHODS: Using PAR(2) gene deletion and other approaches to inhibit or prevent PAR(2) activation, the development and progression of CIA were assessed via clinical and histological scores together with ex vivo immune analyses. RESULTS: The progression of CIA, assessed by arthritic score and histological assessment of joint damage, was significantly (p<0.0001) abrogated in PAR(2) deficient mice or in wild-type mice administered either a PAR(2) antagonist (ENMD-1068) or a PAR(2) neutralising antibody (SAM11). Lymph node derived cell suspensions from PAR(2) deficient mice were found to produce significantly less interleukin (IL)-17 and IFNγ in ex vivo recall collagen stimulation assays compared with wild-type littermates. In addition, substantial inhibition of TNFα, IL-6, IL-1β and IL-12 along with GM-CSF and MIP-1α was observed. However, spleen and lymph node histology did not differ between groups nor was any difference detected in draining lymph node cell subsets. Anticollagen antibody titres were significantly lower in PAR(2) deficient mice. CONCLUSION: These data support an important role for PAR(2) in the pathogenesis of CIA and suggest an immunomodulatory role for this receptor in an adaptive model of inflammatory arthritis. PAR(2) antagonism may offer future potential for the management of inflammatory arthritides in which a proteinase rich environment prevails.
21719521 Rheumatoid hand surgery: differing perceptions amongst surgeons, rheumatologists and thera 2011 Oct Rheumatoid arthritis is a systemic disease that requires coordinated management by rheumatologists, surgical specialists and therapists working in a multidisciplinary team. Differences of opinion within the team may adversely affect patient care. Our aim was to assess differences in perception about rheumatoid hand surgery between rheumatologists, hand surgeons and hand therapists in the UK. We used a postal questionnaire to assess commonly performed rheumatoid hand operations. For each procedure, respondents rated the most important indication for surgery and scored effectiveness at reducing pain, improving function and aesthetics, and preventing deformity. Statistically significant differences were found between all three groups with regards to expected outcome and main indications for surgery. We concluded that significant differences do exist in the perceptions of rheumatologists, surgeons and therapists. Rheumatoid hand operations require more detailed study, clarifying indications and outcome to allow consistent advice to patients from all members of the multidisciplinary team.