Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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24832843 | Economic burden of long-term care of rheumatoid arthritis patients in Hungary. | 2014 May | BACKGROUND AND AIM: Long-term care (LTC) in Hungary is provided in four major ways: day care, nursing, chronic care, and rehabilitation. The aim of this study was to explore the financing of LTC in Hungary, with a disease-specific focus on rheumatoid arthritis (RA) patients. DATA AND METHODS: Data were derived from the National Health Insurance Fund Administration (NHIFA). For 2012, we analyzed the following indicators: number of patients and cases, crude and weighted hospital days, and health insurance expenditure. RESULTS: The annual health insurance expenditure of LTC was 112.6 million EUR in Hungary in 2012 and covered 209,000 patients (225,000 cases). The NHIFA spent 0.69 million EUR for the LTC of 976 patients with RA. The annual health insurance cost per patient was significantly (by 32%) higher for patients with RA (710 EUR) than the average cost of all patients (538 EUR). The average length of stay was also higher for patients with RA (19.7 days) than for the general LTC population (17.4 days). CONCLUSIONS: The cost of LTC of patients with RA is higher than the average cost of the general LTC patient population. Early treatment of RA patients could contribute to decreasing LTC expenditure. More generally, health technology assessment can inform future LTC funding debates in Central and Eastern European countries by putting more emphasis on LTC utilization and costs. | |
25481556 | Seronegative rheumatoid arthritis: pathogenetic and therapeutic aspects. | 2014 Aug | Rheumatoid arthritis (RA) has long been recognised as a highly heterogeneous disease of immune dysregulation. Despite an ever-growing appreciation of the role of circulating autoantibodies in the development of 'seropositive' disease, the pathogenesis of seronegative RA remains poorly understood. Accumulating evidence suggests that RA 'serotypes', in fact, reflect distinct disease entities that, despite their clinical overlap, diverge in respect of genetic architecture, cellular pathology and even therapeutic responsiveness. Focussing on seronegative RA, this review considers these concepts and their implications for the management of patients with this challenging, though sometimes overlooked, condition. | |
23311733 | Standardized grip strength as an outcome measure in early rheumatoid arthritis. | 2013 | OBJECTIVES: Patients with rheumatoid arthritis (RA) suffer progressive loss of hand function and have weaker hand grip than the healthy population. In this study we aimed to validate hand grip strength standardized by age and gender (z score) against currently accepted clinical measures of disease activity. METHOD: Electronic records of patients with a diagnosis of RA seen between April 2007 and December 2011 were screened for the documentation of tender and swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), along with patient global activity score and grip strength. Bilateral grip strengths were converted to z scores on the basis of previously published age- and gender-corrected normative data for grip strength. The z scores were then correlated against components of disease activity scores. RESULTS: Ninety patients diagnosed with RA had been seen 602 times within 2 years of diagnosis. Hand grip data were available for 204 visits. There was a statistically significant inverse correlation between grip strength z scores and the tested variables. The sensitivity and specificity of a hand grip z score of -1.5 for predicting remission were, respectively, 70% and 76% for the right hand and 82% and 69% for the left hand. CONCLUSIONS: Hand grip testing and subsequent conversion to z scores corrected for age and gender correlate with disease activity in early RA. We have shown that the grip strength z scores can discriminate between various disease states, and the strength seems to return to near normative data when the disease is in remission. | |
25114059 | Estimation of heritability of different outcomes for genetic studies of TNFi response in p | 2015 Dec | OBJECTIVES: Pharmacogenetic studies of tumour necrosis factor inhibitors (TNFi) response in patients with rheumatoid arthritis (RA) have largely relied on the changes in complex disease scores, such as disease activity score 28 (DAS28), as a measure of treatment response. It is expected that genetic architecture of such complex score is heterogeneous and not very suitable for pharmacogenetic studies. We aimed to select the most optimal phenotype for TNFi response using heritability estimates. METHODS: Using two linear mixed-modelling approaches (Bayz and GCTA), we estimated heritability, together with genomic and environmental correlations for the TNFi drug-response phenotype ΔDAS28 and its separate components: Δ swollen joint count (SJC), Δ tender joint count (TJC), Δ erythrocyte sedimentation rate (ESR) and Δ visual-analogue scale of general health (VAS-GH). For this, we used genome-wide single nucleotide polymorphism (SNP) data from 878 TNFi-treated Dutch patients with RA. Furthermore, a multivariate genome-wide association study (GWAS) approach was implemented, analysing separate DAS28 components simultaneously. RESULTS: The highest heritability estimates were found for ΔSJC (h(2)gbayz=0.76 and h(2)gGCTA=0.87) and ΔTJC (h(2)gbayz=0.62 and h(2)gGCTA=0.82); lower heritability was found for ΔDAS28 (h(2)gbayz=0.59 and h(2)gGCTA=0.71) while estimates for ΔESR and ΔVASGH were near or equal to zero. The highest genomic correlations were observed for ΔSJC and ΔTJC (0.49), and the highest environmental correlation was seen between ΔTJC and ΔVASGH (0.62). The multivariate GWAS did not generate excess of low p values as compared with a univariate analysis of ΔDAS28. CONCLUSIONS: Our results indicate that multiple SNPs together explain a substantial portion of the variation in change in joint counts in TNFi-treated patients with RA. In conclusion, of the outcomes studied, the joint counts are most suitable for TNFi pharmacogenetics in RA. | |
24170308 | Association of AIRE polymorphisms with genetic susceptibility to rheumatoid arthritis in a | 2014 Apr | Recently, genetic polymorphisms within the autoimmune regulator (AIRE) have been implicated in the genetic susceptibility to rheumatoid arthritis (RA) in Japanese and Spanish. The aim of this case-control study involving 232 patients with RA and 313 ethnically matched control subjects was to investigate the association of AIRE rs2075876 and rs760426 polymorphisms with genetic predisposition to RA in a Chinese population. The genotypes of AIRE rs2075876 and rs760426 polymorphisms were determined by SNaPshot assay. A significant difference in the allele frequency of AIRE rs2075876 polymorphism between cases and controls was detected (A versus G, OR 1.33, 95 %CI 1.04-1.69, P = 0.02, P corrected (Bonferroni correction) Pc = 0.04). Significant evidence was found for the association between the minor allele A of AIRE rs2075876 polymorphism and the risk of RA under the recessive model (AA versus AG + GG, P = 7.15 × 10(-3), Pc = 1.43 × 10(-2)). The frequency of the minor allele G of AIRE rs760426 polymorphism was higher in patients compared with controls (47.8 % versus 42.1 %), and this deviation showed a trend towards significant level (P = 0.06, Pc = 0.12). The association between the minor allele G of AIRE rs760426 polymorphism with RA risk under the dominant model and the recessive model revealed that significant evidence was detected under the recessive model (GG versus GA + AA, P = 0.02, Pc = 0.04). Our results indicated that AIRE rs2075876 and rs760426 polymorphisms were involved in the genetic background of RA in the Chinese population. | |
23397259 | Effects of different local cryotherapies on systemic levels of TNF-α, IL-6, and clinical | 2013 Aug | Cryotherapies are frequently used to supplement the rehabilitation of patients with rheumatoid arthritis (RA) owing to their analgesic and anti-inflammatory effects. Forty patients with active RA were recruited and received 10 days of comprehensive therapy with different local cryotherapies. None of the respondents were subjected to biological treatment. They were divided into two groups according to the therapy received: nitrogen vapour at -160 °C (group I) or cold airflow at -30 °C (group II). Levels of tumour necrosis factor α (TNF-α), interleukin 6 (IL-6), disease activity score (DAS28), and functional variables were used to assess the outcomes. After the therapy, both groups exhibited similar improvements. Significant reduction in TNF-α level (nitrogen: p < 0.01; cold air: p < 0.05) and no change in IL-6 were observed. DAS28, the clinical severity of pain, duration of morning stiffness, degree of self-reported fatigue, and health assessment questionnaire (HAQ) scores improved significantly. In addition, the active range of knee extension, time, and the number of steps in the 50-m walk test also clearly got better in both groups. The 10-day comprehensive therapies including different local cryotherapies for the patients with RA cause significant decrease in TNF-α systemic levels, meaningly improve DAS28, HAQ scores, and some functional parameters, but do not change IL-6 levels. However, there were no differences in the effectiveness of either cryotherapy. | |
24352338 | Is radiographic progression of late-onset rheumatoid arthritis different from young-onset | 2014 Apr | OBJECTIVE: RA can be categorized into late-onset RA (LORA, >60-65 years) and young-onset RA (YORA, 30-55 years), depending on the patient's age at disease onset. Since the average age of the population is continuously increasing, LORA will most probably gain in importance in the future. Despite this growing importance, LORA has not been the focus of much interest in the past. The aim of this study was to analyse radiographic damage progression of early disease in LORA compared with YORA patients. METHODS: We included all patients from the Swiss RA registry, Swiss Clinical Quality Management in RA, with recent-onset arthritis, either RA (disease duration ≤1 year) or undifferentiated arthritis, as diagnosed by the data-entering physician. Patients were followed for 5 years. The cut-off between YORA and LORA was operationally set at 60 years of age. The primary outcome of this study was disease progression and activity, which was assessed based on the 28-joint DAS (DAS28) and the progression of joint erosions using a validated scoring system (Ratingen score). RESULTS: A total of 592 patients with early disease were analysed. The age at disease onset had a Gaussian distribution, with a single peak at 54 years of age; 366 patients were categorized as YORA and 226 as LORA at disease onset. DAS28 scores were significantly higher among LORA as compared with YORA patients (4.8 vs 4.5, P = 0.049). Corticosteroids were used in 68% of LORA patients as a first-line treatment, compared with 25.4% in YORA patients (χ(2) test: 54.58; P < 0.0001). In contrast, DMARDs were used in 100% of the YORA patients as first-line treatment, compared with 91.2% of the LORA patients. During follow-up, new glucocorticoids, synthetic DMARDs or biologic DMARDs were initiated in 32.8%, 61.1% and 14.1% of all YORA patients and 17.5%, 54.6% and 6.6% of LORA patients, respectively (χ(2) test: 7.08, 22.53, 54.4; all P < 0.01). The DAS28 scores decreased in both groups during the observed time period, and the initial differences in disease activity vanished after 6 months and during the subsequent follow-up. The Ratingen score was higher in LORA than in YORA patients at inclusion (12.7 vs 5.6, P < 0.0001). The rate of radiographic progression at 5 years was similar when comparing LORA and YORA (3.3 vs 2.6, respectively, P = 0.64). The Ratingen scores at onset and during follow-up over 5 years did not clearly separate LORA and YORA into two groups, but rather, increased linearly when comparing the patients in groups per decade from 20 to 92 years of age. CONCLUSION: Our results did not show LORA as a separate subgroup of RA with a different prognosis with regard to radiographic progression. | |
22274131 | Inter- and intra-observer agreement of high-resolution ultrasonography and power Doppler i | 2013 Jan | To assess the inter- and intra-observer reproducibility of musculoskeletal ultrasonography among rheumatologist in detecting inflammatory and morphostructural changes in small joints of the hands in patients with rheumatoid arthritis (RA). Five members of the "Escuela de EcografÃa del Colegio Mexicano de ReumatologÃa" tested their inter- and intra-observer reliabilities in the assessment of basic sonographic findings of joint inflammation and bone erosion. Their results were compared to those obtained by a group of international experts from European League Against Rheumatism. A clinical rheumatologist evaluated eight RA patients. Five Siemens Acuson Antares ultrasound machines (7-13 MHz linear probes) were used. The OMERACT preliminary definitions of joint effusion, synovial hypertrophy, bone erosions and tenosynovitis were adopted. Inter-observer and intra-observer agreement was calculated by overall agreement and kappa statistics. Mean kappa value for joint effusion was good, 0.654 (85%); synovial hypertrophy, 0.550 (77.2%); power Doppler signal, 0.550 (82.5%); bone erosions, 0.549 (81%); and tenosynovitis, 0.500 (91.5%). Mean and overall intra-observer agreement for semiquantitative score was good for joint effusion, 0.630 (77.2%) and bone erosions, 0.605 (56.25%); and moderate to synovial hypertrophy, 0.476 (65%) and power Doppler signal, 0.471 (80%). Mean kappa value for joint effusion was 0.381 (95%), synovial hypertrophy, 0.447 (72%); power Doppler signal, 0.496 (81%); bone erosions, 0.294 (81%); and tenosynovitis, 0.030 (66%). Mean and overall inter-observer agreement for semiquantitative score was poor for joint effusion, 0.325 (57%) and bone erosions, 0.360 (43%); and moderate to synovial hypertrophy, 0.431 (55%) and power Doppler signal, 0.496 (81%). Intra-observer variability reached the highest levels of agreement. Factors related to the experience of the rheumatologist, the time spent in each examination and knowledge of the software ultrasound equipment could influence the lower level of inter-observer agreement in this study. | |
25228593 | RADB: a database of rheumatoid arthritis-related polymorphisms. | 2014 Sep 15 | Rheumatoid arthritis (RA) is an autoimmune disease that has a complex genetic basis. Therefore, it is important to explore the genetic background of RA. The extensive recent application of polymorphic genetic markers, especially single nucleotide polymorphisms, has presented us with a large quantity of genetic data. In this study, we developed the Database of Rheumatoid Arthritis-related Polymorphisms (RADB), to integrate all the RA-related genetic polymorphisms and provide a useful resource for researchers. We manually extracted the RA-related polymorphisms from 686 published reports, including RA susceptibility loci, polymorphisms associated with particular clinical features of RA, polymorphisms associated with drug response in RA and polymorphisms associated with a higher risk of cardiovascular disease in RA. Currently, RADB V1.0 contains 3235 polymorphisms that are associated with 636 genes and refer to 68 countries. The detailed information extracted from the literature includes basic information about the articles (e.g., PubMed ID, title and abstract), population information (e.g., country, geographic area and sample size) and polymorphism information (e.g., polymorphism name, gene, genotype, odds ratio and 95% confidence interval, P-value and risk allele). Meanwhile, useful annotations, such as hyperlinks to dbSNP, GenBank, UCSC, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway, are included. In addition, a tool for meta-analysis was developed to summarize the results of multiple studies. The database is freely available at http://www.bioapp.org/RADB. Database URL: http://www.bioapp.org/RADB. | |
24112173 | Combination of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography a | 2013 | BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder. Many methods have been used to observe the progress of RA. The purpose of this study was to observe the progress of RA in rats with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), magnetic resonance (MR) imaging and arthritis score, and analyze the relationships among different methods in evaluation of RA. METHODS: Sixteen healthy Sprague Dawley (SD) rats about 8-week old were randomly assigned to a RA group and a control group. Bovine type II emulsified incomplete Freud's adjuvant was used to induce arthritis in the RA group. Arthritis score of the rats in two groups were recorded, and (18)F-FDG PET/CT, MR imaging were performed both on the corresponding rats every 3 days. All the rats were sacrificed at week 5, and histopathological examination was performed on rat knees stained with haematoxylin and eosin. RESULTS: The arthritis score and the standard uptake value (SUV) of knee joints in RA rats increased with the progression of arthritis gradually. Both peaks of arthritis score and SUV appeared at 21 days after the first immune injection, then the arthritis score and SUV of knee joints decreased slowly. The arthritis scores of knee joints in RA rats were positively correlated with their SUV changes. The MR images were confirmed by the histopathological studies. CONCLUSION: PET/CT can detect the earliest molecular metabolism changes of RA, and MR imaging can follow up the dynamical anatomical changes of RA, all of which indicated that PET/CT and MR imaging may be applied as useful tools to monitor the progress of RA. | |
23955066 | ACPA and bone loss in rheumatoid arthritis. | 2013 Oct | Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by bone loss. Degree of inflammation and autoantibody positivity have both been identified as important initiators of skeletal damage in RA. Whereas it is well appreciated that inflammation initiates bone loss via the action of cytokines, the effect of autoantibodies in initiating bone destruction has long been underestimated. It has, nonetheless, been known for years that antibodies against citrullinated proteins (ACPA) and rheumatoid factor are associated with a more destructive disease course. It was recently shown that ACPA bind osteoclast precursor cells and directly promote their differentiation into bone-resorbing osteoclasts. Other results have shown that in ACPA-positive individuals bone loss starts even before the onset of clinical disease; this is indicative of the independent effect of these antibodies in initiating skeletal damage. The observation that the mere presence of ACPA is associated with pathological changes suggests that these antibodies have functional properties and initiate the onset of disease long before patients consult the rheumatologist because of symptomatic joint disease. These findings also indicate that "RA" is a syndrome rather than a single disease, suggesting that autoantibody-positive patients are both genetically and clinically distinct phenotypes. | |
23147896 | Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors | 2013 Jan | Rheumatoid arthritis (RA) is characterized by hyperplastic synovial pannus tissue, which mediates destruction of cartilage and bone. Fibroblast-like synoviocytes (FLS) are a key component of this invasive synovium and have a major role in the initiation and perpetuation of destructive joint inflammation. The pathogenic potential of FLS in RA stems from their ability to express immunomodulating cytokines and mediators as well as a wide array of adhesion molecule and matrix-modelling enzymes. FLS can be viewed as 'passive responders' to the immunoreactive process in RA, their activated phenotype reflecting the proinflammatory milieu. However, FLS from patients with RA also display unique aggressive features that are autonomous and vertically transmitted, and these cells can behave as primary promoters of inflammation. The molecular bases of this 'imprinted aggressor' phenotype are being clarified through genetic and epigenetic studies. The dual behaviour of FLS in RA suggests that FLS-directed therapies could become a complementary approach to immune-directed therapies in this disease. Pathophysiological characteristics of FLS in RA, as well as progress in targeting these cells, are reviewed in this manuscript. | |
22538842 | Low-level laser therapy in different stages of rheumatoid arthritis: a histological study. | 2013 Feb | Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of unknown etiology. Treatment of RA is very complex, and in the past years, some studies have investigated the use of low-level laser therapy (LLLT) in treatment of RA. However, it remains unknown if LLLT can modulate early and late stages of RA. With this perspective in mind, we evaluated histological aspects of LLLT effects in different RA progression stages in the knee. It was performed a collagen-induced RA model, and 20 male Wistar rats were divided into 4 experimental groups: a non-injured and non-treated control group, a RA non-treated group, a group treated with LLLT (780 nm, 22 mW, 0.10 W/cm(2), spot area of 0.214 cm(2), 7.7 J/cm(2), 75 s, 1.65 J per point, continuous mode) from 12th hour after collagen-induced RA, and a group treated with LLLT from 7th day after RA induction with same LLLT parameters. LLLT treatments were performed once per day. All animals were sacrificed at the 14th day from RA induction and articular tissue was collected in order to perform histological analyses related to inflammatory process. We observed that LLLT both at early and late RA progression stages significantly improved mononuclear inflammatory cells, exudate protein, medullary hemorrhage, hyperemia, necrosis, distribution of fibrocartilage, and chondroblasts and osteoblasts compared to RA group (p < 0.05). We can conclude that LLLT is able to modulate inflammatory response both in early as well as in late progression stages of RA. | |
24223933 | Circulating CD4+CD161+ T lymphocytes are increased in seropositive arthralgia patients but | 2013 | Improved understanding of the immune events discriminating between seropositive arthralgia and clinical synovitis is of key importance in rheumatology research. Ample evidence suggests a role for Th17 cells in rheumatoid arthritis. We hypothesized that CD4+CD161+ cells representing Th17 lineage cells may be modulated prior to or after development of clinical synovitis. Therefore, in a cross-sectional study, we investigated the occurrence of CD4+CD161+ T-cells in seropositive arthralgia patients who are at risk for developing rheumatoid arthritis and in newly diagnosed rheumatoid arthritis patients. In a prospective study, we evaluated the effect of methotrexate treatment on circulating CD4+CD161+ T-cells. Next, we assessed if these cells can be detected at the level of the RA joints. Precursor Th17 lineage cells bearing CD161 were found to be increased in seropositive arthralgia patients. In contrast, circulating CD4+CD161+T-cells were decreased in newly diagnosed rheumatoid arthritis patients. The decrease in CD4+CD161+ T-cells correlated inversely with C-reactive protein and with the 66 swollen joint count. Methotrexate treatment led to normalization of CD4+CD161+ T-cells and reduced disease activity. CD4+CD161+ T cells were readily detected in synovial tissues from both early and late-stage rheumatoid arthritis. In addition, synovial fluid from late-stage disease was found to be enriched for CD4+CD161+ T-cells. Notably, synovial fluid accumulated CD4+CD161+T-cells showed skewing towards the Th1 phenotype as evidenced by increased interferon-γ expression. The changes in peripheral numbers of CD4+CD161+ T-cells in seropositive arthralgia and early rheumatoid arthritis and the enrichment of these cells at the level of the joint predict a role for CD4+CD161+ T-cells in the early immune events leading to clinical synovitis. Our findings may add to the development of RA prediction models and provide opportunities for early intervention. | |
24251619 | Inhibitory effect of tacrolimus on progression of joint damage in patients with rheumatoid | 2014 Sep | AIM: To examine the inhibitory effect of tacrolimus on radiographic joint damage in patients with rheumatoid arthritis (RA). METHODS: Thirty-eight patients with RA resistant or intolerant to conventional disease-modifying anti-rheumatic drugs were administered tacrolimus and analyzed retrospectively. Disease activity and clinical response were evaluated by Disease Activity Score in 28 joints and C-reactive protein (DAS28-CRP) and European League Against Rheumatism (EULAR) response criteria. The progression of joint destruction was evaluated by an estimated yearly change in modified Total Sharp Score (mTSS). RESULTS: Good or moderate response rate according to EULAR response criteria was seen in 63.2%, 63.2%, 73.7% and 65.8% of patients at 3, 6, 12, and 24 months, respectively. The rate of patients with low disease activity or remission reached 47.3% and 50.0% at 12 and 24 months, respectively. Progression of joint damage, evaluated as yearly change in mTSS (ΔmTSS), significantly decreased from 11.4 at baseline to 2.63 in the first year and 0.69 in the second year of tacrolimus treatment. CONCLUSION: These findings suggest tacrolimus has the potential to inhibit progression of joint damage in established RA. | |
25011635 | Pain related catastrophizing on physical limitation in rheumatoid arthritis patients. Is a | 2014 | The experience of Rheumatoid Arthritis (RA) includes significant suffering and life disruption. This cross-sectional study examined the associations between pain, catastrophizing, acceptance and physical limitation in 55 individuals (11 males and 44 female; Mean age = 54.37; SD = 18.346), from the Portuguese population with (RA) 2 years after the diagnosis; also explored the role of acceptance as a mediator process between pain, catastrophizing and physical limitation. Results showed positive correlation between pain and catastrophizing (r = .544; p ≤ .001), and also between pain and 2-years' physical limitation (r = .531; p ≤ .001) Results also showed that acceptance was negatively correlated with physical limitation 2 years after the diagnosis (r = -.476; p ≤ .001). Path-analysis was performed to explore the direct effect of pain (ß = -.393; SD = .044; Z = 3.180; p ≤ .001) and catastrophizing (n.sig.) on physical limitation and also to explore the buffer effect of acceptance in this relationship (indirect effect ß = -.080). Results showed that physical limitation is not necessarily a direct product of pain and catastrophizing but acceptance was also involved. Pain and catastrophizing are associated but the influence of catastrophizing on physical limitation is promoted by low levels of acceptance. Results emphasize the relevance of acceptance as the emotional regulation process by which pain and catastrophizing influence physical functioning and establish the basic mechanism by which pain and catastrophizing operate in a contextual-based perspective. Also the study results offer a novel approach that may help behavioral health and medical providers prevent and treat these conditions. | |
23620106 | The Th17 pathway as a therapeutic target in rheumatoid arthritis and other autoimmune and | 2013 Oct | Production of the pro-inflammatory cytokine interleukin (IL)-17 by Th17 cells and other cells of the immune system protects the host against bacterial and fungal infections, but also promotes the development of rheumatoid arthritis (RA) and other autoimmune and inflammatory disorders. Several biologicals targeting IL-17, the IL-17 receptor, or IL-17-related pathways are being tested in clinical trials, and might ultimately lead to better treatment for patients suffering from various IL-17-mediated disorders. In this review, we provide a clear overview of current knowledge on Th17 cell regulation and the main Th17 effector cytokines in relation to IL-17-mediated conditions, as well as on recent IL-17-related drug developments. We demonstrate that targeting the Th17 pathway is a promising treatment for rheumatoid arthritis and various other autoimmune and inflammatory diseases. However, improvements in technical developments assisting in the identification of patients suffering from IL-17-driven disease are needed to enable the application of tailor-made, personalized medicine. | |
25504938 | United States Physical Therapists' Knowledge About Joint Hypermobility Syndrome Compared w | 2016 Mar | BACKGROUND: Joint hypermobility syndrome (JHS) is one of the most common inherited connective tissue disorders. It causes significant pain and disability for all age groups, ranging from developmental delay among children to widespread chronic pain in adults. Experts in JHS assert that the condition is under-recognized and poorly managed. PURPOSE: The aim of this study was to assess US physical therapists' knowledge about JHS compared with other causes of widespread pain and activity limitations: fibromyalgia, juvenile rheumatoid arthritis and adult rheumatoid arthritis. METHODS: Cross-sectional, Internet-based survey of randomly selected members of the American Physical Therapy Association and descriptive statistics were used to explore physical therapists' knowledge about JHS, fibromyalgia, juvenile rheumatoid arthritis and adult rheumatoid arthritis, and chi square was used to compare knowledge about the different conditions. RESULTS: The response rate was 15.5% (496). Although 36% recognized the Beighton Scale for assessing joint hypermobility, only 26.8% of respondents were familiar with the Brighton Criteria for diagnosing JHS. Few respondents (11-19%) realized that JHS has extra-articular features such as anxiety disorder, fatigue, headache, delayed motor development, easy bruising and sleep disturbance. Physical therapists working in environments most likely to see patients with JHS underestimated the likely prevalence in their patient population. CONCLUSIONS: The results suggest that many physical therapists in the United States are not familiar with the diagnostic criteria, prevalence or common clinical presentation of JHS. | |
23835879 | Clinical features and independent predictors in the further development of rheumatoid arth | 2013 Nov | This study aims to investigate the prognosis of undifferentiated arthritis (UA) and to estimate the putative predictors contributing to predict the development of UA into rheumatoid arthritis (RA); thus, it could improve appropriate medical intervention. A retrospective cohort study of 218 patients with an initial diagnosis of UA and 2-year follow-up monitoring was carried out. The baseline information including demographic variables, clinical features, and laboratory data was collected. A logistic regression model was used for the statistical analysis. After 2 years of follow-up, 20.18% of UA patients evolved into RA, but 33.03% remained undifferentiated. Meanwhile, 25.23% went into remission, and 21.56% developed into other connective tissue diseases. Univariate and multivariate analysis showed that the titer of antibodies to cyclic citrullinated peptide (anti-CCP), tender joint count and duration of morning stiffness were independent predictors for the development of RA. The area under the curve (AUC) of duration of morning stiffness (0.81) was largest, followed by tender joint count (0.74). The AUC of anti-CCP antibodies (0.68) was higher than that of rheumatoid factor of IgM type (IgM-RF) (0.60), and the combination of these two antibodies was significantly higher than each alone (P < 0.001). In conclusion, UA patients had variable clinical outcomes and prognosis. Only the titer of anti-CCP antibodies, tender joint count, and duration of morning stiffness, instead of IgM-RF, could predict the development of RA. Although the anti-CCP antibody was better than the IgM-RF in predicting RA, a combined detection of them still improved the diagnostic performance. | |
24106838 | Turkish experience in rheumatoid arthritis patients with clinical apparent amyloid deposit | 2013 Dec | OBJECTIVES: We evaluated the frequency of clinical apparent amyloid deposition, clinical features and outcome in our rheumatoid arthritis (RA) patients. METHODS: Medical records of 1415 RA patients were examined. During routine follow-up, RA patients with proteinuria on urinalysis, underwent rectal biopsy. RESULTS: Eleven patients (0.78%) were diagnosed with clinical apparent amyloid deposition. While the mean annual incidence of AA amyloidosis between 2001 and 2005 was 0.2%, it was 0.13% between 2006 and 2011. At initial presentation, three RA-related AA amyloidosis patients had nephrotic-range proteinuria and renal insufficiency, four had only nephrotic-range proteinuria, three had non-nephrotic-range proteinuria, and one had non-nephrotic-range proteinuria and renal insufficiency. The mean age in RA patients with AA amyloidosis was 60.8 years and disease duration was 12 years. Ten of 11 cases had positive rheumatoid factor. Two RA patients with AA amyloidosis who had been diagnosed in the pre-anti-TNF era died. Of the rest nine patients with AA amyloidosis, eight were administered anti-TNF therapy and one was given rituximab. In four patients, anti-TNF therapy led to disappearance of clinical features, decrement in proteinuria and resulted in improvement of or at least stabilization of renal functions. One patient using anti-TNF therapy died because of tuberculosis. One patient discontinued anti-TNF therapy and developed end-stage renal disease. Two patients have been started to be given anti-TNF therapy recently. In one patient who was given rituximab, there was regression of proteinuria and improvement in renal functions. CONCLUSIONS: We diagnosed a 0.78% frequency of AA amyloidosis in RA. It seems that - other than the risks of infection, tuberculosis - anti-TNF drugs seem to be effective on RA disease activity and also have renoprotective effects in RA patients with AA amyloidosis. |