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ID PMID Title PublicationDate abstract
25073584 "Better but not best": a qualitative exploration of the experiences of occupational gain f 2015 OBJECTIVES: To investigate whether patients with improved clinical markers during their anti-TNFα treatment experience improvements in their functional and psychological ability to undertake activities. METHODS: Patients receiving anti-TNFα treatment for rheumatoid arthritis (RA) or ankylosing spondylitis (AS) were recruited from outpatient clinics in East Anglia and North West England. Purposive sampling recruited variety in demographic and treatment experiences. Data were collected through in-depth qualitative interviews and analysed using an interpretive phenomenological framework. Twenty-seven patients were recruited; 19 with RA, eight with AS, and aged from 21 to 73 years. RESULTS: While people generally experienced an improvement in their functional ability, known as occupational gain, they continued to experience difficulties through previous biomechanical damage, continuing symptoms of inflammatory arthritis, or concerns about anti-TNFα treatment. These disruptions affected how participants retained or regained employment. Lack of healthcare support, including an absence of occupational therapy intervention, resulted in people testing new boundaries through a process of unsupported trial and error. CONCLUSION: Occupational gain was not maximised for people on anti-TNFα treatment. Improved referral pathways to occupational therapy could facilitate the management of continuing functional difficulties, thereby maximising the benefit of treatment to people with inflammatory arthritis.
25546988 [Welfare as the goal of the analgesic pharmacotherapy accompanying biological treatment in 2014 Nov Therapy of chronic rheumatic diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS) needs a comprehensive approach to the patient, based on the control of pain and improvement in overall condition, which affects the quality-of-life. This requires optimizing the treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or analgesics and control of adverse drug reactions. The aim of the study was to evaluate the efficacy and safety of pain pharmacotherapy in patients with rheumatoid arthritis and ankylosing spondylitis treated as the basic pharmacotherapy-biological drugs, the analysis of awareness of pharmacovigilance and evaluation of analgesic treatment costs. Material and methods. Examined group consisted of 102 people with RA or AS received biological therapy. Test method was questionnaire with closed and open questions. Results. 86.2% of respondents used a pain medication (41%--an ad hoc basis, but 23%--at least once a day), while 79.4%--NSAIDs (33%--an ad hoc basis and 17%--at least once a day). In 85.3% of those not observed adverse effects of pain pharmacotherapy. 5 persons declared abdominal pain. Most of the patients complied with the recommendations of the doctor in the pain treatment. For the third respondents the cost of pharmacotherapy of pain was monthly 1-10 zl, but 6% of patients paying for drugs from 50-60 and above 60 zl monthly. Conclusions. Biological treatment in RA and AS is effective but requires additional analgesic therapy. Adverse effects seen during pharmacological treatment of chronic pain in rheumatic diseases are, in practice sporadic. Therapeutic patient education with chronic diseases is proper. Costs borne by the patient's pain relief in this group are not too high.
24085550 Screening for latent tuberculosis infection in patients with chronic inflammatory arthriti 2013 Dec OBJECTIVE: Screening for latent tuberculosis infection (LTBI) is mandatory before initiating biologics in patients with chronic inflammatory arthritis (CIA). However, few studies have evaluated the discrepancies between the results of tuberculin skin test (TST) and interferon-γ release assays (IGRA) in these patients. The purpose of our study was to investigate factors associated with TST and IGRA results in a large cohort of patients with CIA before the introduction of biologics. METHODS: A total of 563 consecutive patients with CIA (293 rheumatoid arthritis, 270 spondyloarthritis) and eligible for biologics were prospectively enrolled. Demographic, clinical, and biological data were recorded. Risk factors for LTBI were assessed. All patients underwent a TST, a chest radiograph, and an IGRA test (T-SPOT.TB). RESULTS: Agreement between the 2 tests was low (κ = 0.16). The bacillus Calmette-Guerin (BCG) status was significantly associated with discordance between the 2 tests (p = 0.004). The TST positivity rate was 34.8%. Factors associated with a negative TST were female sex (p = 0.02) and immunosuppressive treatment (p = 0.003). The only LTBI risk factor associated with TST positivity was an abnormal chest radiograph (p = 0.02). T-SPOT.TB was positive in 21.7% of patients and indeterminate in 15.6%. Previous active TB and chest radiograph abnormalities were associated with IGRA positivity (p = 0.008 and p = 3.9 × 10(-5), respectively). The BCG vaccination was associated with negative IGRA (p = 3 × 10(-4)). Indeterminate IGRA results were associated with age, C-reactive protein, and immunosuppressive treatment (p = 0.005, 0.007, and 0.004, respectively). CONCLUSION: Our data support the combined use of T-SPOT.TB and TST in patients with CIA before biologics introduction. However, despite these good diagnostic values, indeterminate results may complicate the use of IGRA.
24654999 Certolizumab pegol in rheumatoid arthritis: current update. 2014 Jun INTRODUCTION: The development of TNF-α inhibitors (TNF-is) represents a major advancement in the treatment of rheumatoid arthritis (RA). Currently, there are five agents licensed for moderate-to-severely active RA. Certolizumab pegol (CZP) is a novel PEGylated, constant fragment-free TNF-i therapy, which is the focus of this review. AREAS COVERED: Data from Phase III randomised controlled trials in terms of clinical efficacy, radiographic progression, patient-reported outcomes and safety profile are reviewed. These include long-term data from open-label extension studies. EXPERT OPINION: The advantages of CZP include rapid reduction of disease activity, low rates of injection-site reaction and may be safe for use in pregnancy. The long-term data strengthen the position of CZP for use either as monotherapy or preferably in combination with disease modifying anti-rheumatic drugs (DMARDs), in moderate-to-severely active RA, comparable to other TNF-is. Notably, prolonged CZP exposure is not associated with increased risk of severe infection compared to general population, contrasting with preliminary analysis of short-term data. Over the next few years, evidence will be available on the use of CZP in combination with methotrexate for remission induction in DMARD-naïve patients, biomarkers and the development and licensing of TNF-i biosimilars.
25553833 Overview of biologic treatments in the elderly. 2015 May As life expectancies rise, the number of elderly people with inflammatory rheumatic diseases will continue to grow. Treatment of this frail population, whose clinical features differ from those of younger subjects, poses new challenges to healthcare systems. However, this issue is rarely addressed in the current literature. Thanks to their targeted mechanism of action, biologics represent one of the major therapeutic advances of the last 15 years, but their use in the elderly has been slow in developing. Published data, derived mainly from cohorts, focus on the use of TNF inhibitors in rheumatoid arthritis and show that these treatments are effective and generally well tolerated. Nevertheless, the risk of infection and cancer, particularly skin and lymphoid malignancies, must not be neglected. The use of these biologics as second-line treatment improves patient outcomes and comfort, while reducing consumption of the widely used and more deleterious drugs such as glucocorticoids and non-steroidal anti-inflammatory drugs. Additional studies on biologics, focusing on the longer term and in indications apart from anti-TNF therapies in rheumatoid arthritis should help overcome some of the reluctance and promote the rational use of these drugs in the elderly.
23704464 Endoscopic resection of the inflamed bicipitoradial bursa extended around the radial neck. 2013 May 22 The bicipitoradial bursa lies at the insertion of the biceps tendon on the radial tuberosity. It is an unusual site for chronic bursitis and most often, results from repetitive mechanical trauma or overuse. Other causes include tuberculosis, immunological complications of the rheumatological disease, for example, psoriatic arthropathy, rheumatoid arthritis and synovial chondromatosis. Unlike ganglion cyst arising from the elbow joint, resection of the bursa through the elbow arthroscopy is not possible as the bursa is not communicated with the joint. We reported a patient with rheumatoid arthritis presenting with bicipitoradial bursitis extended around the radial neck which was successfully resected endoscopically.
23739921 Effects of isotonic and isometric hand exercises on pain, hand functions, dexterity and qu 2013 Oct The primary objective of our study was to evaluate the effect of 6-week-long isotonic and isometric hand exercises on pain, hand functions, dexterity and quality of life in women diagnosed as rheumatoid arthritis (RA). Our secondary objective was to assess the changes in handgrip strength and disease activity. This randomized, parallel, single-blinded 6-week intervention study enrolled 52 female patients between 40 and 70 years of age, who were diagnosed with RA according to American College of Rheumatology criteria, had disease duration of at least 1 year and had a stage 1-3 disease according to Steinbrocker's functional evaluation scale. Patients were randomized into isotonics and isometrics groups. Exercises were performed on sixth week. All patients were applied wax therapy in the first 2 weeks. Their pain was assessed with visual analog scale (VAS), their hand functions with Duruöz Hand Index (DHI), dexterity with nine hole peg test (NHPT) and quality of life with Rheumatoid Arthritis Quality of Life questionnaire (RAQoL). Dominant and non-dominant handgrip strengths (HS) were measured. Disease activity was determined by disease activity score (DAS 28). We evaluated the difference in the above parameters between baseline and 6 weeks by Wilcoxon paired t test. The study was completed with 47 patients (isotonics n = 23; isometrics n = 24). VAS, DHI, NHPT, and RAQoL scores significantly improved in both groups by the end of 6th week compared to the baseline scores of the study (for isotonics p = 0.036, p = 0.002; p = 0.0001, p = 0.003; for isometrics p = 0.021, p = 0.002, p = 0.005, p = 0.01, respectively). DAS 28 scores decreased in both exercise groups (p = 0.002; p = 0.0001, respectively), while isometrics showed a significant increase in dominant HS (p = 0.029), and isotonics showed a significant increase in non-dominant HS (p = 0.013). This study showed that isometric and isotonic hand exercises decrease pain and disease activity and improve hand functions, dexterity and quality of life as well as mildly increasing muscle strength in patients diagnosed as RA.
23739182 Differential expression of proteins with heparin affinity in patients with rheumatoid and 2013 Sep OBJECTIVES: Using proteomic approach in this study, we sought to identify proteins with heparin affinity associated with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and non-inflammatory arthritis (NIA). METHODS: Plasma samples from adult RA, PsA and NIA patients, 20 of each, were collected. After enrichment of proteins with heparin affinity, SDS-PAGE and in-gel digestion with trypsin were performed. Peptides were concentrated, micro-purified, separated and measured by nano-scale HPLC system coupled to a mass spectrometer. Peak lists were generated from raw spectra and searched against human complete proteome set by MaxQuant software. Statistical analysis of protein relative expression levels was done in IPython interactive Python shell using NumPy and Matplotlib libraries. Individual protein impact on the whole dataset correlation was done by excluding one protein at a time and calculating the correlation coefficient of remaining data points. RESULTS: Three hundred and eighty-four different proteins were identified keeping false discovery rate to 1%, from which 163 were identified in all three conditions. The plasma proteome showed a good correlation between rheumatoid (RA) and psoriatic arthritis (PsA). Out of 10 proteins whose impact on the correlation coefficient fell outside of two standard deviations from the mean, four were up-regulated (complement factor I, complement component C8 beta, glyceraldehyde-3-phosphate dehydrogenase and inter-alpha-trypsin inhibitor heavy chain H1), and two were down-regulated (immunoglobulin heavy chain V-III region BRO, and immunoglobulin J chain), both in PsA and RA by a similar ratio when compared to NIA. The remaining four proteins (Serpin A11, complement factor H-related protein 5, cartilage acidic protein 1 and coagulation factor IX) were down-regulated in PsA and up-regulated in RA when compared to NIA. CONCLUSIONS: We found differently expressed proteins in patients with inflammatory and non-inflammatory rheumatic conditions. Out of 384 proteins with heparin affinity four proteins should be further validated as potential diagnostic biomarkers in patients with RA and PsA.
24350725 SLC19A1 80G allele as a biomarker of methotrexate-related gastrointestinal toxicity in Por 2014 Apr AIM: The aim of our study was to characterize the association of clinicopathological variables and the SLC19A1/RFC-1 G80A polymorphism in methotrexate (MTX)-related toxicity in Portuguese patients with rheumatoid arthritis. PATIENTS & METHODS: The study included 233 consecutively recruited patients with rheumatoid arthritis under MTX treatment. The SLC19A1 G80A polymorphism was evaluated by PCR-RFLP. RESULTS: Statistical analysis revealed that SLC19A1 80G carriers had increased risk of gastrointestinal toxicity (odds ratio [OR]: 2.61, p = 0.019) and that regular folic acid supplementation was associated with both overall and gastrointestinal toxicity protection (OR: 0.15, p < 0.001 and OR: 0.19, p < 0.001, respectively). Multivariate analysis confirmed the association of SLC19A1 80G and regular folic acid supplementation to gastrointestinal toxicity (OR: 5.53 and 0.13, respectively). Moreover, a multivariate Cox regression model demonstrated a higher risk of earlier gastrointestinal toxicity in SLC19A1 80G carriers (hazard ratio: 3.63, p = 0.002). CONCLUSION: SLC19A1 G80A genotyping may be a useful tool for clinicians to identify patients at higher risk for developing gastrointestinal toxicity related to MTX treatment.
23819865 Smoking-related emphysema is associated with idiopathic pulmonary fibrosis and rheumatoid 2013 Nov BACKGROUND AND OBJECTIVE: A combined pulmonary fibrosis/emphysema syndrome has been proposed, but the basis for this syndrome is currently uncertain. The aim was to evaluate the prevalence of emphysema in idiopathic pulmonary fibrosis (IPF) and rheumatoid lung (rheumatoid arthritis-interstitial lung disease (RA-ILD)), and to compare the morphological features of lung fibrosis between smokers and non-smokers. METHODS: Using high-resolution computed tomography, the prevalence of emphysema and the pack-year smoking histories associated with emphysema were compared between current/ex-smokers with IPF (n = 186) or RA-ILD (n = 46), and non-chronic obstructive pulmonary disease (COPD) controls (n = 103) and COPD controls (n = 34). The coarseness of fibrosis was compared between smokers and non-smokers. RESULTS: Emphysema, present in 66/186 (35%) patients with IPF and 22/46 (48%) smokers with RA-ILD, was associated with lower pack-year smoking histories than in control groups (P < 0.05 for all comparisons). The presence of emphysema in IPF was positively linked to the pack-year smoking history (odds ratio 1.04, 95% confidence interval (CI) 1.02-1.06, P < 0.0005). In IPF, fibrosis was coarser in smokers than in non-smokers on univariate and multivariate analysis (P < 0.01 for all comparisons). In RA-ILD, fibrosis was coarser in patients with emphysema but did not differ significantly between smokers and non-smokers. CONCLUSIONS: In IPF and RA-ILD, a high prevalence of concurrent emphysema, in association with low pack-year smoking histories, and an association between coarser pulmonary fibrosis and a history of smoking in IPF together provide support for possible pathogenetic linkage to smoking in both diseases.
25138129 Identification of myeloid-derived suppressor cells in the synovial fluid of patients with 2014 Aug 19 BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of innate immune cells with a granulocyte-like or monocyte-like phenotype and a unique ability to suppress T-cell responses. MDSCs have been shown to accumulate in cancer patients, but recent studies suggest that these cells are also present in humans and animals suffering from autoimmune diseases. We previously identified MDSCs in the synovial fluid (SF) of mice with experimental autoimmune arthritis. The goal of the present study was to identify MDSCs in the SF of patients with rheumatoid arthritis (RA). METHODS: RA SF cells were studied by flow cytometry using antibodies to MDSC cell surface markers as well as by analysis of cell morphology. The suppressor activity of RA SF cells toward autologous peripheral blood T cells was determined ex vivo. We employed both antigen-nonspecific (anti-CD3/CD28 antibodies) and antigen-specific (allogeneic cells) induction systems to test the effects of RA SF cells on the proliferation of autologous T cells. RESULTS: SF from RA patients contained MDSC-like cells, the majority of which showed granulocyte (neutrophil)-like phenotype and morphology. RA SF cells significantly suppressed the proliferation of anti-CD3/CD28-stimulated autologous T cells upon co-culture. When compared side by side, RA SF cells had a more profound inhibitory effect on the alloantigen-induced than the anti-CD3/CD28-induced proliferation of autologous T cells. CONCLUSION: MDSCs are present among RA SF cells that are commonly regarded as inflammatory neutrophils. Our results suggest that the presence of neutrophil-like MDSCs in the SF is likely beneficial, as these cells have the ability to limit the expansion of joint-infiltrating T cells in RA.
23385275 Opioid analgesics for rheumatoid arthritis pain. 2013 Feb 6 CLINICAL QUESTION Do the benefits of opioid analgesics outweigh the risks in patients with persistent pain due to rheumatoid arthritis? BOTTOM LINE Weak opioids (such as codeine, dextropropoxyphene, and tramadol) may be effective in the short-term management of rheumatoid arthritis pain, but adverse effects are common and may outweigh the benefits; alternative analgesics should be considered first.
24410774 Real-world effectiveness of abatacept for rheumatoid arthritis treatment in European and C 2014 Jan 11 BACKGROUND: Discontinuation of rheumatoid arthritis (RA) treatment for lack or loss of initial response, tolerability issues, or development of antibodies against the therapeutic agent remains a challenge in clinical practice. Here we present a 6-month interim analysis of a 2-year prospective observational trial in Europe and Canada aiming to assess the real-world effectiveness, safety, and tolerability of intravenous abatacept for the treatment of moderate-to-severe RA. METHODS: ACTION (AbataCepT In rOutiNe clinical practice) is a prospective, observational study assessing effectiveness, safety, and tolerability of abatacept in patients with RA enrolled in Europe and Canada between May 2008 and January 2011. The patient population was divided into two groups: biologic naïve ('first-line') patients and patients who had previously failed treatment with at least one biologic agent ('second-line'). Retention rates were calculated using Kaplan-Meier curve estimates. Effectiveness was measured using European League Against Rheumatism (EULAR) response criteria, the 28-item Disease Activity Score, the Clinical Disease Activity Index (CDAI), and physical function, as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI). Serious adverse events (SAEs) were reported for all enrolled patients. RESULTS: Of 1138 consecutively enrolled patients, 1114 and 1079 patients were evaluable for retention and effectiveness, respectively. Overall, retention rates were 88.6% (95% confidence interval [CI]: 86.4, 90.4); 67.4% of patients achieved good/moderate EULAR response; 32.8% had a CDAI Low Disease Activity State (LDAS); and 44.7% a HAQ-DI response. Retention rates among first- and second-line patients were 93.0% (95% CI: 85.9, 96.6) and 88.1% (95% CI: 85.7, 90.0), respectively. The percentage of patients achieving CDAI LDAS was 40.0% (95% CI: 26.4, 53.6) for first- and 32.2% (95% CI: 28.4, 36.0) for second-line patients and the proportion achieving a HAQ-DI response was 60.3% (95% CI: 47.8, 72.9) versus 43.1% (95% CI: 39.0, 47.2), respectively. The incidence of SAEs was 4.7%. CONCLUSIONS: Evidence from this 6-month interim analysis suggests that abatacept offers an effective and well-tolerated treatment option for patients with RA, including those who have previously failed anti-tumor necrosis factor treatment. In addition, higher retention rates and effectiveness outcomes were observed when abatacept treatment was initiated earlier in the course of the disease.
24003684 [Changes in social relations as a consequence of rheumatoid arthritis and osteoarthritis]. 2013 Patients with rheumatoid arthritis (RA) and osteoarthritis (OA) suffer from a lot of pain, have difficulties with movement, so it is therefore logical for them to have less social contact, i.e. socializing with friends and family. Aim of the study was to examine social relations of the patients with RA and OA, and to establish the reasons for such relations. Survey conducted 55 patients, 29 patients with RA and 26 patients with knee OA. From all patients data from domain of social contacts have been taken. They filled in self-evaluation scale for depression by Zung-SDS, and functional ability was assessed by Health Assessment Questionnaire HAQ (for RA) and by Laquesne index (for OA). Most patients in both groups narrowed the number of people with whom they socialize 82.8% RA patients and 80.7% OA patients and now they socialize with the closest family. Able to socialize are 31% RA patients and 53 % OA patients. Daily pain cites 71% RA patients and 64% OA patients. Depression is present by most of the patients, 82.8 % RA patients, and 73.1% OA patients. Functional ability is decreased by all patients, slightly more by RA patients. Most examined patients narrowed the number of people with whom they socialize, where RA patients feel more unable for going for visit. The reason for decreased social contact is not just reduced functional ability, and daily pain, but also depression that is present in high percentage in both groups, more and in higher level by patients with RA.
24204851 Anti-angiogenic effect of triptolide in rheumatoid arthritis by targeting angiogenic casca 2013 Rheumatoid arthritis (RA) is characterized by a pre-vascular seriously inflammatory phase, followed by a vascular phase with high increase in vessel growth. Since angiogenesis has been considered as an essential event in perpetuating inflammatory and immune responses, as well as supporting pannus growth and development of RA, inhibition of angiogenesis has been proposed as a novel therapeutic strategy for RA. Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F, has been extensively used in treatment of RA patients. It also acts as a small molecule inhibitor of tumor angiogenesis in several cancer types. However, it is unclear whether triptolide possesses an anti-angiogenic effect in RA. To address this problem, we constructed collagen-induced arthritis (CIA) model using DA rats by the injection of bovine type II collagen. Then, CIA rats were treated with triptolide (11-45 µg/kg/day) starting on the day 1 after first immunization. The arthritis scores (P<0.05) and the arthritis incidence (P<0.05) of inflamed joints were both significantly decreased in triptolide-treated CIA rats compared to vehicle CIA rats. More interestingly, doses of 11~45 µg/kg triptolide could markedly reduce the capillaries, small, medium and large vessel density in synovial membrane tissues of inflamed joints (all P<0.05). Moreover, triptolide inhibited matrigel-induced cell adhesion of HFLS-RA and HUVEC. It also disrupted tube formation of HUVEC on matrigel and suppressed the VEGF-induced chemotactic migration of HFLS-RA and HUVEC, respectively. Furthermore, triptolide significantly reduced the expression of angiogenic activators including TNF-α, IL-17, VEGF, VEGFR, Ang-1, Ang-2 and Tie2, as well as suppressed the IL1-β-induced phosphorylated of ERK, p38 and JNK at protein levels. In conclusion, our data suggest for the first time that triptolide may possess anti-angiogenic effect in RA both in vivo and in vitro assay systems by downregulating the angiogenic activators and inhibiting the activation of mitogen-activated protein kinase downstream signal pathway.
23515858 MicroRNA-223: a double-edged sword in rheumatoid arthritis. 2014 Feb Increased expression of microRNA-223 (miR-223) has been demonstrated in rheumatoid arthritis (RA) patients. Two research teams focus recently on the underlying mechanisms mediated by miR-223 but two stories are developed in opposite ways.
22850768 Erosive wrist and hand arthritis: is it a rare manifestation of Behçet's disease? 2013 Oct It is believed that arthritis in Behçet's disease is usually non-erosive and non-destructive. We report herein a 72-year-old female who presented with Behçet's disease and an erosive arthritis of the bilateral elbow, wrist, and metacarpophalangeal and proximal interphalangeal joints, radiologically mimicking rheumatoid arthritis.
23486415 Lysophosphatidic acid receptor inhibition as a new multipronged treatment for rheumatoid a 2014 Jan OBJECTIVE: To investigate the effect of lysophosphatidic acid (LPA) receptor inhibition in a mouse model of autoantibody-mediated arthritis. METHODS: Arthritis was induced in C57BL/6 mice by K/BxN serum transfer. Arthritic mice were treated with the LPA receptor antagonist, Ki16425 and arthritis severity was assessed clinically and histologically. Expression of inflammatory mediators in joints was identified by a mouse cytokine array and validated by western blot and real-time PCR assays. Effects of treatment with LPA receptor antagonist or with small interfering RNA on bone metabolism were assessed by in vitro assays of osteoclastogenesis, bone resorption, osteoblasts differentiation and bone mineralisation. RESULTS: Mice treated with the LPA receptor antagonist Ki16425 showed attenuated arthritis characterised by reduction of synovial inflammation, cartilage damage and, more markedly, bone erosion. We detected increased apoptosis, reduction of inflammatory mediators and of bone remodelling proteins in arthritic joints from mice treated with Ki16425. In addition, we demonstrated that inhibition or suppression of LPA1 receptor reduces osteoclast differentiation and bone resorption and, on the contrary, it promotes differentiation of osteoblasts and bone mineralisation. CONCLUSIONS: Pharmacological inhibition of LPA1 receptor in the K/BxN serum-transfer arthritis model led to reduction of severity of arthritis involving multiple mechanisms, increased apoptosis, reduced inflammatory mediators and proteins involved in bone remodelling, that show LPA1 as a very promising target in rheumatoid arthritis treatment.
24550170 Smoking induces transcription of the heat shock protein system in the joints. 2014 Jul OBJECTIVES: Smoking increases the risk of developing rheumatoid arthritis (RA) and worsens the course of the disease. In the current study we analysed whether smoking can affect gene expression directly in the joints. METHODS: Synovial fibroblasts were incubated with 5% cigarette smoke extract and changes in gene expression were detected using whole genome microarrays and verified with real-time PCR. Synovial tissues were obtained from smoking and non-smoking patients with RA undergoing joint replacement surgery and from mice exposed to cigarette smoke or ambient air in a whole body exposure chamber for 3 weeks. RESULTS: Microarray and real-time PCR analysis showed a significant upregulation of the heat shock proteins DnaJA4, DnaJB4, DnaJC6, HspB8 and Hsp70 after stimulation of synovial fibroblasts with 5% cigarette smoke extract. Similarly, in synovial tissues of smokers with RA the expression of DnaJB4, DnaJC6, HspB8 and Hsp70 was significantly higher compared with non-smokers with RA. Upregulation of DnaJB4 and DnaJC6 in joints by smoking was also confirmed in mice exposed to cigarette smoke. CONCLUSIONS: Our data clearly show that smoking can change gene expression in the joints, which can lead to the activation of signalling pathways that promote development of autoimmunity and chronic joint inflammation.
23592598 Accuracy of Canadian health administrative databases in identifying patients with rheumato 2013 Oct OBJECTIVE: Health administrative data can be a valuable tool for disease surveillance and research. Few studies have rigorously evaluated the accuracy of administrative databases for identifying rheumatoid arthritis (RA) patients. Our aim was to validate administrative data algorithms to identify RA patients in Ontario, Canada. METHODS: We performed a retrospective review of a random sample of 450 patients from 18 rheumatology clinics. Using rheumatologist-reported diagnosis as the reference standard, we tested and validated different combinations of physician billing, hospitalization, and pharmacy data. RESULTS: One hundred forty-nine rheumatology patients were classified as having RA and 301 were classified as not having RA based on our reference standard definition (study RA prevalence 33%). Overall, algorithms that included physician billings had excellent sensitivity (range 94-100%). Specificity and positive predictive value (PPV) were modest to excellent and increased when algorithms included multiple physician claims or specialist claims. The addition of RA medications did not significantly improve algorithm performance. The algorithm of "(1 hospitalization RA code ever) OR (3 physician RA diagnosis codes [claims] with ≥1 by a specialist in a 2-year period)" had a sensitivity of 97%, specificity of 85%, PPV of 76%, and negative predictive value of 98%. Most RA patients (84%) had an RA diagnosis code present in the administrative data within ±1 year of a rheumatologist's documented diagnosis date. CONCLUSION: We demonstrated that administrative data can be used to identify RA patients with a high degree of accuracy. RA diagnosis date and disease duration are fairly well estimated from administrative data in jurisdictions of universal health care insurance.