Browse

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

ID PMID Title PublicationDate abstract
25198103 Assessment of wrist joint inflammation in patients with rheumatoid arthritis by quantitati 2014 Sep OBJECTIVES: We aimed to compare the use of computer-aided quantification methods with 3 different power Doppler ultrasonography (PDUS) modes to assess wrist inflammation in patients with rheumatoid arthritis (RA). METHODS: This study enrolled 49 patients (60 hand joints) with RA. Clinical parameters (rheumatoid factor [RF], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]) were measured and pain was evaluated by a visual analogue scale (VAS, range: 0 to 10). Imaging of the affected wrist joints was performed with 2D- and 3D-PDUS imaging. The 2D imaging used a volumetric transducer and a linear transducer and the 3D imaging employed a volumetric transducer. Software was used to calculate the vascularisation index (VI), flow index (FI), and vascularisation flow index (VFI) under different measurement conditions. RESULTS: There were 8 males and 41 females, with an average age of 47.59±15.17 years, and average VAS score of 3.63±2.22. In 2D-PDUS with a linear probe, there were significant correlations of ESR with VI and VFI, and of CRP with area, VI, and VFI (p<0.05 for all comparisons). In 3D-PDUS, there was a significant correlation of CRP with VFI (p<0.05). In all 3 measurement modes, there were moderate or high levels of inter- and intra-operator agreement in measurement of area/volume, VI, FI, and VFI. CONCLUSIONS: All 3 PDUS measurement modes had high accuracy and reliability in assessment of wrist inflammation. These results suggest that use of a 3D transducer, which is more expensive and time-consuming, is not necessary for assessment of wrist inflammation.
23892853 Sexual dysfunction in women with rheumatoid arthritis. 2013 Aug AIM: Rheumatoid Arthritis (RA) is a widespread disease which leads to various degrees of disability and profound impact on overall life quality of the patient with regard to social, economic, psychological and sexual aspects. It may be assumed that RA can affect sexual function. The aim of this study was to evaluate the sexual function in female subjects with RA. METHODS: A total of 186 married women (age range 30-60 years) were included in this study. Of the total participants, 104 were RA patients and 82 were healthy women. Hospital anxiety and depression scale (HADS), Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS) were used to evaluate the differences between the controls and patient group. Sexual functions were evaluated using the validated Female Sexual Function Index (FSFI). RESULTS: The mean age of the RA patients and controls was 46.71 ± 7.65 and 43.98 ± 7.97, respectively. According to the total sexual function score evaluation, 97 out of 104 women with RA (93.7 %) and in 53 out of 82 women in control group (64.6 %) were regarded as having sexual dysfunction (SD). There was significant difference between these two subgroups with regard to only depression factor. CONCLUSION: Current results have demonstrated that patients with RA have had a higher sexual dysfunction rate, when compared with the control group. SD may be related to perceived depression, which are frequently encountered conditions in patients with RA.
25799826 [The clinical significance of hepcidin detection in the patients with anemia and rheumatoi 2014 The prevalence of anemia in patients with rheumatoid arthritis (RA) varies from 30 to 70%. 25% of the cases are diagnosed within 1 year after onset of the disease. On the whole, anemia in RA is described as anemia of a chronic disease (ACD). Pathogenesis ofACD is a multifactor process underlain by an immune mechanism: cytokines and cells ofthe reticuloendothelial system cause changes in iron homeostasis, proliferation of erythroid precursors, erythropoietin production and lifespan of erythrocytes. The key pathogenetic factor is disordered iron metabolism. IL-6 increasing hepatic production acute-phase protein (hepcidin) is the most important cytokine involved in ACD pathogenesis. Hence the necessity to measure its serum level for differential diagnostics of anemic syndrome in patients with RA and the choice of effective basal therapy. Recent data on the therapeutic potency of tocilizumab (IL-6 receptor inhibitor) demonstrate not its safety and sustainable beneficial clinical effect in combination with the favourable action on hemoglobin profile and reduction offatigue.
24489017 TNFAIP3 gene polymorphisms associated with differential susceptibility to rheumatoid arthr 2014 Jun OBJECTIVE: We investigated the relationship between polymorphisms in the TNF-a-induced protein 3 (TNFAIP3) gene and genetic susceptibility to SLE and RA in the Korean population. METHODS: The present case control study included 422 patients with RA, 133 patients with SLE and 422 healthy controls. Genotyping for TNFAIP3 gene polymorphisms rs5029941 (C>T), rs2230926 (T>G), rs5029930 (C>A), rs5029937 (G>T) and rs5029939 (G>C) in TNFAIP3 gene polymorphisms was performed. The status of RA-related autoantibodies, including RF and anti-CCP, in RA and the presence of arthritis and nephritis in SLE were assessed. RESULTS: Significantly different frequencies of minor alleles in two TNFAIP3 polymorphisms were found in patients with SLE compared with healthy controls [odds ratio (OR) 2.13, 95% CI 1.25, 3.65, P= 0.02 for rs5029937; OR 2.17, 95% CI 1.27, 3.72, P= 0.01 for rs5029939). Moreover, patients with SLE showed different frequencies of haplotypes compared with healthy controls (P<0.001). However, no association was found between RA susceptibility and TNFAIP3 polymorphisms (P= 0.28). Interactions between RA-related autoantibody status and TNFAIP3 polymorphisms were not associated with RA susceptibility. Interestingly, arthritis in patients with SLE was marginally associated with TNFAIP3 polymorphisms (P= 0.04). CONCLUSION: The results suggest that TNFAIP3 gene polymorphisms are associated with differential susceptibility to SLE and RA in the Korean population. The relationship between TNFAIP3 gene polymorphisms and RA susceptibility may be dependent on ethnic background.
24300151 [Detection significance of Th17 cells in peripheral blood of patients with rheumatoid arth 2013 Aug 6 OBJECTIVE: To explore the significance and evaluate the early structural erosion through the expressions of Th17 cells in peripheral blood of patients with rheumatoid arthritis (RA) in clinical remission. METHODS: A total of 41 active RA patients without structural erosion were selected. Intracelluar flow cytometric detection of Th17 cells in peripheral blood was performed. And the supernatant level of interleukin (IL)-17A was determined simultaneously in RA patients and control groups at baseline and endpoint of 24-month therapy. The correlations were analyzed between Th17 cells and RA disease activity index DAS28. They were classified into radiographic progression (P, n = 10) and radiographic non-progression groups (NP, n = 26) by the Sharp/van der Heijde score (SHS) at the endpoint. The differences of Th17 cells and IL-17A levels were analyzed between P (SHS > 0.5) and NP groups (SHS ≤ 0.5). RESULTS: The expression of Th17 cells in active RA patients was significantly higher than that of controls [(1.63 ± 0.45)% vs (0.91 ± 0.26)%, P < 0.01]. And the results of IL-17A level were similar [1510 ± 280) vs (320 ± 31) ng/L, P < 0.05]. The expression of Th17 cells was positively correlated with DAS28 score (r = 0.87, P < 0.01). Thirty-six RA patients were followed up at the endpoint and all of them stayed in clinical remission (DAS28 < 2.6). The peripheral blood expressions of Th17 cells of P group were significantly higher than those of NP group . At the same time, no differences of IL-17A levels existed between two groups. CONCLUSION: Structural erosion still progresses in some RA patients despite an apparent clinic remission. And a high-level peripheral expression of Th17 hints at structural erosion.
24389486 Therapeutic effects of gel ointments containing tranilast nanoparticles on paw edema in ad 2014 Tranilast (TL), an antiallergic agent, has been clinically used in the treatment of bronchial asthma, although its clinical use has been limited by its poor solubility in water, photodegradation and systemic side effects. In this study, we prepared a gel ointment containing TL nanoparticles (TLnano gel ointment), and investigated its usefulness. In addition, we demonstrated the preventive effects of the TLnano gel ointment on inflammation in adjuvant-induced arthritis (AA) rats. The TLnano gel ointment was prepared using Bead Smash 12 (a bead mill) and additives including sodium docusate, 2-hydroxypropyl-β-cyclodextrin, methylcellulose and Carbopol 934; the mean particle diameter of the TL nanoparticles was 71.0±25.4 nm. In in vitro skin penetration experiments, the amount of penetrated TL, the penetration rate (Jc) and the penetration coefficient through the skin (Kp) of the TLnano gel ointment were significantly higher than those of a gel ointment containing TL microparticles (TLmicro gel ointment; particle diameter 50.5±26.3 µm). The TL concentrations in the skin tissue and plasma of rats receiving the TLnano gel ointment were also higher than in rats receiving the TLmicro gel ointment. In addition, the application of the TLnano gel ointment attenuated the increase in paw edema of the hind feet of AA rats in comparison with AA rats treated with the TLmicro gel ointment. These results suggest that TL nanoparticles can be applied to the formulation of a transdermal system, and that a transdermal formulation using TL nanoparticles might be a delivery option for the clinical treatment of RA.
23445732 [Case of successful pregnancy and childbirth in a rheumatoid arthritis patient treated wit 2013 The patient was a 34-year-old woman who, at age 23, was diagnosed with rheumatoid arthritis (RA) presenting with morning stiffness, swelling and tenderness of bilateral knee joints and metacarpophalangeal (MP) joints of the right second and third fingers, increased C-reactive protein (CRP) levels, and a high level of rheumatoid factor (RF). The patient was maintaining remission with oral dose of bucillamine (BUC; 300 mg/day); however, due to the deterioration of arthralgia at age 26, she was additionally administered 8 mg/week of methotrexate (MTX), which improved the symptoms. Thereafter, the prescription of BUC was discontinued. At age 31, she experienced onsets of swelling and tenderness in both the knee joints and wrists and in MP joints of the right second and third fingers; further, CRP levels increased to 5.44 mg/dL, resulting in increased RA activity. The concomitant administration of infliximab was started at a dose of 3 mg/kg, which helped achieve favorable RA control. At age 32, approximately 2 years before childbirth, the prescription of infliximab was changed to 25 mg/dose of etanercept administered twice a week because the patient wished to conceive. Remission was maintained even after the drug change; therefore, MTX was discontinued and the patient was treated with etanercept alone. After she was confirmed to be pregnant in March of the following year, administration of etanercept was continued for treating of RA even during pregnancy. During that time, RA was favorably controlled, and the patient gave birth to a baby boy weighing 3192 g in October of the same year. The Apgar score of the baby was favorable. This case is considered important because, to the best of our knowledge, this may be the first report of a planned pregnancy and childbirth in a patient under administration of a biological preparation.
24667579 Peripheral CD4CD8 double positive T cells with a distinct helper cytokine profile are incr 2014 Peripheral CD4CD8 double positive (DP) T cells have been reported to play a role in several autoimmune diseases, virus infections and cancer. In rheumatoid arthritis (RA), both CD4 and CD8 single positive (SP) T cells are known to be involved in the pathogenesis, but the role of peripheral CD4CD8 DP T cells has not been investigated in detail. Anti cyclic citrullinated antibodies (ACPA) positive and ACPA negative RA patients, patients with systemic lupus erythematodes (SLE) and age matched healthy donors (HD) were enrolled in the analysis. The frequencies and phenotype of DP T cells in PBMC were investigated. In addition, DP T cells were quantified in biopsies from rheumatoid synovium. After in vitro restimulation, the cytokine production of DP T cells was investigated in cultures of PBMC. CMV specific cytokine secretion as well as proliferation was analyzed following antigen specific restimulation after an appropriate culture duration. DP T cells were found more frequently in RA patients than in healthy controls or patients with SLE. These DP T cells express αβ TCRs, are of a memory phenotype and share features of both CD4 as well as CD8 SP T cells. Importantly, DP T cells were found to also be present in the rheumatoid synovium. Further characterization of DP T cells from RA patients revealed increased production of IL-21 and IL-4, implying a possible role as T helper cells. In addition, DP T cells in RA seem to contribute to the inflammatory process, because they produce significantly more IFNγ than counterparts from HD and are increased in CMV+ RA patients. Given their capacity to produce a variety of cytokines (IL4, IL21 and IFNγ), their association with ACPA positive RA and their presence in the synovium, we suggest an important role of double positive T cells in the pathogenesis of rheumatoid arthritis.
24659492 Detecting the violation of variance homogeneity in mixed models. 2016 Dec Mixed-effects models are increasingly used in many areas of applied science. Despite their popularity, there is virtually no systematic approach for examining the homogeneity of the random-effects covariance structure commonly assumed for such models. We propose two tests for evaluating the homogeneity of the covariance structure assumption across subjects: one is based on the covariance matrices computed from the fitted model and the other is based on the empirical variation computed from the estimated random effects. We used simulation studies to compare performances of the two tests for detecting violations of the homogeneity assumption in the mixed-effects models and showed that they were able to identify abnormal clusters of subjects with dissimilar random-effects covariance structures; in particular, their removal from the fitted model might change the signs and the magnitudes of important predictors in the analysis. In a case study, we applied our proposed tests to a longitudinal cohort study of rheumatoid arthritis patients and compared their abilities to ascertain whether the assumption of covariance homogeneity for subject-specific random effects holds.
25471471 Discontinuation of tumour necrosis factor inhibitors in patients with rheumatoid arthritis 2015 Jun BACKGROUND: There is increasing interest in discontinuing biological therapies for patients with rheumatoid arthritis (RA) achieving good clinical responses, provided patients maintain clinical benefit. METHODS: We assessed patients with RA from the Corrona registry who discontinued treatment with their first tumour necrosis factor inhibitor (TNFi) while in low-disease activity (LDA) or lower levels of disease activity. Patients were followed until they lost clinical benefit, defined as increased disease activity or change in RA medications. Duration of maintenance of clinical benefit was estimated using the Kaplan-Meier method. Cox proportional hazard models were assessed to identify factors related to maintenance of benefit. RESULTS: We identified 717 eligible patients with RA from 35,656 in the Corrona registry. At discontinuation, patients had a median RA duration of 8 years, mean clinical disease activity score of 4.3±0.11; 41.8% were using TNFi as monotherapy. 73.4% of patients maintained benefit for >12 months after discontinuing therapy and 42.2% did so through 24 months. Factors predictive of maintaining clinical benefit in multivariate analysis included lower disease activity, less pain and better functional status at the time of TNFi discontinuation. Among 301 patients initiating their first TNFi within the registry, faster responders (ie, those who achieved LDA in 4 months or less) did better than slower responders (HR 1.54 (95% CI 1.17 to 2.04)). RA disease duration did not affect maintenance of clinical benefit. CONCLUSIONS: Discontinuation of a first course of TNFi may be associated with persistent clinical benefit. Half of patients maintained response through 20 months. Several patient characteristics may help predict persistent benefit.
24121751 Sleep apnea and cervical spine pathology. 2014 Mar PURPOSE: Sleep apnea is a multi-factorial disease with a variety of identified causes. With its close proximity to the upper airway, the cervical spine and its associated pathologies can produce sleep apnea symptoms in select populations. The aim of this article was to summarize the literature discussing how cervical spine pathologies may cause sleep apnea. METHODS: A search of the PubMed database for English-language literature concerning the cervical spine and its relationship with sleep apnea was conducted. Seventeen published papers were selected and reviewed. RESULTS: Single-lesion pathologies of the cervical spine causing sleep apnea include osteochondromas, osteophytes, and other rare pathologies. Multifocal lesions include rheumatoid arthritis of the cervical spine and endogenous cervical fusions. Furthermore, occipital-cervical misalignment pre- and post-cervical fusion surgery may predispose patients to sleep apnea. CONCLUSIONS: Pathologies of the cervical spine present significant additional etiologies for producing obstructive sleep apnea in select patient populations. Knowledge of these entities and their pathophysiologic mechanisms is informative for the clinician in diagnosing and managing sleep apnea in certain populations.
25005704 Is there still a role for abatacept in the treatment of lupus? 2014 Sep INTRODUCTION: The quest for safer and more effective treatments for systemic lupus erythematosus (SLE) has led to the development of many new biologic therapies. Abatacept is the first drug targeting co-stimulation between T cells and antigen presenting cells, with abundant pre-clinical evidence to support its use in SLE. AREAS COVERED: This review will present the relevant aspects of lupus pathophysiology pertaining to the mechanism of action of abatacept, a summary of murine studies and the latest human clinical trials. EXPERT OPINION: Abatacept has demonstrated efficacy in both rheumatoid arthritis and psoriatic arthritis, and earlier studies have suggested tantalising evidence of efficacy in SLE. However, the latest randomised double-blinded study showed disappointingly negative results, much like the case of rituximab in SLE. Currently, abatacept remains a possible therapeutic option as an off-label therapy, and it is a part of our therapeutic armamentarium in difficult cases. The need to find appropriate definitions of response and optimal study design continues to be paramount in the field of lupus therapies.
24196988 Body composition of rheumatoid arthritis patients in the City of Cape Town, South Africa. 2014 Apr Patients with rheumatoid arthritis (RA) tend to have a poor nutritional status. This study aimed to gather information on body composition in patients with RA in private and public health settings in the City of Cape Town, South Africa (SA). This cross-sectional study evaluated adults with RA. Information on demographics, comorbidities and medication was gathered. Anthropometrical measurements included weight, height, waist circumference and skinfolds and were used to calculate, interpret and classify body mass index (BMI), percentage body fat, waist circumference, fat mass index (FMI) and fat-free mass index (FFMI). Ethics approval for the execution of the study was obtained from the Health Research Ethics Committee of Stellenbosch University. The study included 251 participants [mean age, 54.7 years; ±standard deviation (SD) 13.6]. The mean BMI was 30.3 kg/m(2) (±SD 6.7) and 26.6 kg/m(2) (±SD 6.1) for women and men, respectively. BMI was used to classify obesity (45.9 %), overweight (26.8 %), normal weight (25.6 %) and underweight (1.6 %). Waist circumference classifications showed a substantially increased risk for metabolic complications in 127 participants (51.8 %) and an increased risk in 52 participants (21.2 %). Low fat-free mass (FFMI of <10th percentile) was seen in 24 participants (21 %), and obesity (FMI of >90th percentile) was seen in 31 (27 %). Rheumatoid cachexia was identified in 12 participants (10.3 %). Results indicate suboptimal nutritional status in patients with RA in the current setting. It highlights the importance of involving dietitians in the management of RA, with a view to reduce symptoms, improve quality of life, prevent cardiovascular disease and decrease overall medical costs.
23553485 Brief report: citrullination within the atherosclerotic plaque: a potential target for the 2013 Jul OBJECTIVE: To investigate whether citrullinated proteins within the atherosclerotic plaque can be targeted by anti-citrullinated protein antibodies (ACPAs), forming stimulatory immune complexes that propagate the progression of atherosclerosis. METHODS: Protein lysates prepared from atherosclerotic segments of human aorta were assessed for the presence of citrulline-modified proteins, and specifically citrullinated fibrinogen (Cit-fibrinogen), by immunoprecipitation and/or immunoblotting followed by mass spectrometry. Immunohistochemical analysis of coronary artery plaque was performed to determine the presence of citrullinated proteins and peptidylarginine deiminase type 4 (PAD-4). Serum levels of anti-cyclic citrullinated peptide (anti-CCP), anti-citrullinated vimentin (anti-Cit-vimentin), and anti-Cit-fibrinogen antibodies were measured in 134 women with seropositive rheumatoid arthritis; these subjects had previously been characterized for the presence of subclinical atherosclerosis, by electron beam computed tomography scanning. RESULTS: Western blot analysis of atherosclerotic plaque lysates demonstrated several citrullinated proteins, and the presence of Cit-fibrinogen was confirmed by immunoprecipitation and mass spectrometry. Immunohistochemical analysis showed colocalization of citrullinated proteins and PAD-4 within the coronary artery plaque. In age-adjusted regression models, antibodies targeting Cit-fibrinogen and Cit-vimentin, but not CCP-2, were associated with an increased aortic plaque burden. CONCLUSION: Citrullinated proteins are prevalent within atherosclerotic plaques, and certain ACPAs are associated with the atherosclerotic burden. These observations suggest that targeting of citrullinated epitopes, specifically Cit-fibrinogen, within atherosclerotic plaques could provide a mechanism for the accelerated atherosclerosis observed in patients with RA.
25515682 Tumor necrosis factor mediates temporomandibular joint bone tissue resorption in rheumatoi 2015 Apr OBJECTIVE: To investigate if TNF, IL-1 or their endogenous controls, in relation to ACPA, are associated with radiological signs of ongoing temporomandibular joint (TMJ) bone tissue resorption and disc displacement in RA patients. METHODS: Twenty-two consecutive outpatients with TMJ of RA were included. Systemic inflammatory activity was assessed by DAS28. The number of painful regions in the body and ESR, CRP, RF and ACPA were analyzed. TMJ synovial fluid and blood samples were obtained and analyzed for TNF, TNFsRII, IL-1ra, IL-1sRII and ACPA. The ratios between the mediators and their endogenous control receptors were used in the statistical analysis. Magnetic resonance imaging was performed in closed- and open-mouth positions and evaluated regarding disc position and presence of condylar and temporal erosions of the TMJ. RESULTS: A high TNF level in relation to TNFsRII in TMJ synovial fluid correlated to the degree of TMJ condylar erosion. A high IL-1ra level in relation to TNF in TMJ synovial fluid was also correlated to the degree of TMJ condylar erosion. The total degree of TMJ condylar erosion was correlated with the number of painful regions. CONCLUSION: This study indicates that TNF in TMJ synovial fluid mediates TMJ cartilage and bone tissue resorption in RA. The study also suggests that the degree of endogenous cytokine control is of importance for development of bone tissue destruction.
24363501 Impact of temporomandibular joint pain in rheumatoid arthritis. 2013 To investigate the impact of temporomandibular joint (TMJ) pain on daily activities and quality of life in relation to systemic inflammatory activity in patients with rheumatoid arthritis (RA), thirty-three consecutive outpatients with RA were included. TMJ pain intensity at rest, on maximum mouth opening, and on chewing was assessed on a 0-10 numerical rating scale. TMJ palpatory tenderness, degree of anterior open bite, the impact of TMJ pain on daily activities and quality of life were also assessed. The systemic inflammatory activity was estimated by the disease activity score 28 (DAS28), blood levels of inflammatory markers and number of painful musculoskeletal regions. TMJ pain at rest, on maximum mouth opening, and on chewing as well as DAS28 was correlated with the impact of the TMJ pain on daily activities and quality of life. Partial correlations showed a significant interaction between TMJ pain on movement and DAS28 that explained the TMJ pain impact on daily activities and quality of life to a significant degree. This study indicates that both current TMJ pain intensity and systemic inflammatory activity play roles in the impact of TMJ pain on daily living and quality of life in RA.
23975359 Assessment of the dimensions, construct validity, and utility for rheumatoid arthritis scr 2014 May This study aims to evaluate the structural validity of the Community-Oriented Program for the Control of Rheumatic Diseases (COPCORD) core instrument as a screening tool for rheumatoid arthritis (RA) by means of assessing the existence of domains in the questionnaire. The Mexican version of the COPCORD instrument was applied to individuals over18 years of age in five regions of the country through a probabilistic/convenience household survey. Clinical confirmation of RA diagnosis was used. The variables analyzed included self-reported comorbidities and manifestations of the disease, as well as sociodemographic characteristics. The statistical approach was based on polychoric exploratory factor analysis and confirmatory factor analysis by means of probit structural equation models. A total of 19,213 subjects were included in the analysis. The average age for the total sample was 42.89 years old; 40.64 % of the subjects were older than 45 years of age and 20.42 % older than 55. More than 80 % of the variation was related to three underlying factors: recent pain, historical pain, and disability. The findings verified the usefulness of the COPCORD instrument as a screening tool for RA. The results also allowed to characterize how the variation in terms of manifestations of the disease could be accounted for diagnosing the disease in the Mexican context and examined the capabilities of the instrument to measure correctly the main characteristics of patients suffering from RA.
23335702 [Prevalence of dyslipidemia and elevated cardiovascular risk in patients with rheumatoid a 2013 The objectives of this study were to compare the frequency of dyslipidemia (DLP) and the elevated cardiovascular risk between rheumatoid arthritis (RA) patients and a control group, to identify disease-related factors associated with the presence of DLP and to estimate the frequency of RA patients receiving treatment for DLP. This is a cross sectional study that included 409 RA patients and 624 controls. Cardiovascular (CV) risk was determined using the Framingham score, National Cholesterol Education Program (NCEP) and the Systematic Coronary Risk Evaluation (SCORE) adapted versions according to the European League Against Rheumatism (EULAR) guidelines. DLP was defined according to the Adult Treatment Panel III (ATPIII). The frequency of CV risk was similar in RA patients and controls, except when NCEP-EULAR adapted version for RA was applied (7% vs. 2%; p = 0.00002). A 43% of patients and 47% of controls had DLP (p = 0.15). RA patients with DLP tended to have extra-articular manifestations more frequently (36% vs. 24%; p = 0.01) and higher erythrocyte sedimentation rate (ESR) (21 [13-35] vs. 18 [10-30] mm; p = 0.003). RA patients treated for DLP varied between 11% and 32% according to the definition used. Patients with RA showed an elevated CV risk only when the NCEP-EULAR definition was used. Among RA patients, those with higher ESR and the presence of extra-articular manifestations were more likely to show DLP. The vast majority of patients were not receiving treatment for DLP.
25288786 Quality of life and unmet needs in patients with inflammatory arthropathies: results from 2015 May OBJECTIVE: The observational RAPSODIA (RA, PsA and spondylitis including AS) study was planned to assess, in patients with RA, AS and PsA, their involvement in medical decisions, quality of life and unmet needs 15 years after the introduction of biologic therapies in Italy. METHODS: Patients completed a questionnaire during their scheduled rheumatology consultation. They rated their satisfaction with disease knowledge on a 5-point scale (1 = not at all satisfied, 5 = totally satisfied). Self-efficacy, defined as judgement of one's own ability to achieve given levels of performance and exercise control over events, was measured using the pain subscale of the Arthritis Self-Efficacy Scale. Patients' global assessments of pain, fatigue and disease activity were recorded on 100 mm visual analogue scales (0 = best status, 100 = worse status). Disease activity status was assessed using standard tools. Health status was measured using the 36-item Short Form Health Survey and the Italian version of the HAQ. RESULTS: Ninety-eight per cent of patients reported that their health care practitioner used understandable terms to explain their condition. Joint issues and general symptoms (e.g. fatigue and malaise) were common. All measures of disease activity and self-efficacy scores were markedly better in patients receiving biologic vs conventional therapy. Biologic therapy recipients were more productive at work. CONCLUSION: These results confirm that some patients with rheumatic diseases are not satisfied with the level of information they receive about their treatments. Biologic therapy appears to be an important advance, with patients receiving this form of treatment having improved symptoms and productivity. However, patients still report unmet needs. Thus further research, and perhaps new and more effective therapies, along with better education and multidisciplinary collaboration, are required to improve outcomes.
25378349 TGFβ responsive tyrosine phosphatase promotes rheumatoid synovial fibroblast invasiveness 2016 Jan OBJECTIVE: In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) that line joint synovial membranes aggressively invade the extracellular matrix, destroying cartilage and bone. As signal transduction in FLS is mediated through multiple pathways involving protein tyrosine phosphorylation, we sought to identify protein tyrosine phosphatases (PTPs) regulating the invasiveness of RA FLS. We describe that the transmembrane receptor PTPκ (RPTPκ), encoded by the transforming growth factor (TGF) β-target gene, PTPRK, promotes RA FLS invasiveness. METHODS: Gene expression was quantified by quantitative PCR. PTP knockdown was achieved using antisense oligonucleotides. FLS invasion and migration were assessed in transwell or spot assays. FLS spreading was assessed by immunofluorescence microscopy. Activation of signalling pathways was analysed by Western blotting of FLS lysates using phosphospecific antibodies. In vivo FLS invasiveness was assessed by intradermal implantation of FLS into nude mice. The RPTPκ substrate was identified by pull-down assays. RESULTS: PTPRK expression was higher in FLS from patients with RA versus patients with osteoarthritis, resulting from increased TGFB1 expression in RA FLS. RPTPκ knockdown impaired RA FLS spreading, migration, invasiveness and responsiveness to platelet-derived growth factor, tumour necrosis factor and interleukin 1 stimulation. Furthermore, RPTPκ deficiency impaired the in vivo invasiveness of RA FLS. Molecular analysis revealed that RPTPκ promoted RA FLS migration by dephosphorylation of the inhibitory residue Y527 of SRC. CONCLUSIONS: By regulating phosphorylation of SRC, RPTPκ promotes the pathogenic action of RA FLS, mediating cross-activation of growth factor and inflammatory cytokine signalling by TGFβ in RA FLS.