Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 28058499 | [Rheumatoid arthritis]. | 2017 Feb | Therapy reduction in rheumatoid arthritis (RA) is still a challenge for physicians as well as for patients. Effective therapy with subsequent achievement of low disease activity or even remission is achievable for numerous patients using currently available treatment options. Therapy discontinuation has therefore become a hot topic and the risk of exacerbation of well-controlled RA must be weighed against the medical and economic benefits of reducing or even discontinuing therapy. This article gives a review of data regarding tapering of therapy in RA, focusing on conventional disease-modifying antirheumatic drug (DMARD) monotherapy, reduction of conventional therapy under continuing therapy with biologics and discontinuation of biologics. Important influencing factors for a safe and successful tapering procedure appear to be disease activity, disease duration and the tapering process itself (i.e. gradual dose reduction vs. abrupt discontinuation). Additionally, the so-called nocebo effect should also be taken into consideration for interpretation of drug tapering studies. | |
| 28786276 | [PRECLINICAL RHEUMATOID ARTHRITIS]. | 2017 Jul | Rheumatoid arthritis affects around 1% of the population. The disease is characterized by joint inflammation and damage. Therapy with disease modifying drugs (DMARDs) has been proved to be efficient in decreasing disease activity and progress, along with improvement in symptoms and prevention of structural damage. The sooner the therapy is initiated, the better the outcome, probably due to a decreased burden of inflammation. The therapeutic potential of early treatment led to an accelerating interest in the preclinical phase of the disease. Many studies demonstrated that there is a preclinical period that precedes the development of clinical arthritis, and the old assumption that the disease develops with the clinical symptoms is no longer valid. Apparently, many biological markers, including autoantibodies, appear years before the clinical synovitis develops. This period is called preclinical rheumatoid arthritis. In the preclinical phase, autoantibodies such as rheumatoid factor, antibodies to citrullinated proteins and many other antibodies and inflammatory markers are abundant. These findings and the evidence of genetic and environmental risk factors for rheumatoid arthritis support the theory which claims that multiple factors contribute to the development of an autoimmune process that progresses and expands until reaching a critical point where rheumatoid arthritis develops. | |
| 29367523 | [The pathogenic role of ACPA in rheumatoid arthritis]. | 2017 | Â Â In rheumatoid arthritis (RA), ACPA (anti-citrullinated protein/peptide antibody) is elevated with high specificity, and clinically, anti-CCP (cyclic citrullinated peptide) antibody is widely used for diagnosis of RA. It is thought ACPAs are produced with genetic background such as HLA-DR, environmental factors such as periodontal disease and smoking, however, the pathogenic role of ACPA in RA has not been elucidated. These were showed immune complexes including ACPA or ACPA itself promoted inflammatory cytokine production such as TNF. PADs (peptidylarginine deiminases) were expressed and citrullinated proteins existed in RA synovium. ACPAs were deposited on the site of citrulline in CD68 positive cells of RA synovium. The damage of bone and cartilage is observed in RA. It was also suggested that deposition of ACPAs caused osteoclastogenesis and bone loss. We introduce several findings about the pathogenic role of ACPA in RA. | |
| 28555384 | Genetics of rheumatoid arthritis susceptibility, severity, and treatment response. | 2017 Jun | A decade after the first genome-wide association study in rheumatoid arthritis (RA), a plethora of genetic association studies have been published on RA and its clinical or serological subtypes. We review the major milestones in the study of the genetic architecture of RA susceptibility, severity, and response to treatment. We set the scientific context necessary for non-geneticists to understand the potential clinical applications of human genetics and its significance for a stratified approach to the management of RA in the future. | |
| 28360422 | Immunometabolism in early and late stages of rheumatoid arthritis. | 2017 May | One of the fundamental traits of immune cells in rheumatoid arthritis (RA) is their ability to proliferate, a property shared with the joint-resident cells that form the synovial pannus. The building of biomass imposes high demands for energy and biosynthetic precursors, implicating metabolic control as a basic disease mechanism. During preclinical RA, when autoreactive T cells expand and immunological tolerance is broken, the main sites of disease are the secondary lymphoid tissues. Naive CD4(+) T cells from patients with RA have a distinct metabolic signature, characterized by dampened glycolysis, low ATP levels and enhanced shunting of glucose into the pentose phosphate pathway. Equipped with high levels of NADPH and depleted of intracellular reactive oxygen species, such T cells hyperproliferate and acquire proinflammatory effector functions. During clinical RA, immune cells coexist with stromal cells in the acidic milieu of the inflamed joint. This microenvironment is rich in metabolic intermediates that are released into the extracellular space to shape cell-cell communication and the functional activity of tissue-resident cells. Increasing awareness of how metabolites regulate signalling pathways, guide post-translational modifications and condition the tissue microenvironment will help to connect environmental factors with the pathogenic behaviour of T cells in RA. | |
| 28217907 | Diet and Rheumatoid Arthritis Symptoms: Survey Results From a Rheumatoid Arthritis Registr | 2017 Dec | OBJECTIVE: Patients with rheumatoid arthritis (RA) often ask whether specific foods, popularized as inflammatory or antiinflammatory, can improve or worsen their RA. Patients with RA took a survey on diet and RA symptoms, and the survey data were collected and analyzed. METHODS: A dietary survey was mailed to 300 subjects in a single-center RA registry at a large academic center. Subjects were asked about their consumption of 20 foods and whether these foods make their RA symptoms better, worse, or unchanged. Semiannual registry data include demographics, medications, comorbidities, and disease activity scores. Fisher's exact test and Wilcoxon's rank sum tests evaluated associations between subject characteristics from the most recent registry assessment and changes in RA symptoms from specific foods. RESULTS: Of the 217 subjects (72% response rate), 83% were female; the median RA duration was 17 years (interquartile range 9-27 years), and 58% were taking a biologic disease-modifying antirheumatic drug. Twenty-four percent of subjects reported that foods affect their RA symptoms, with 15% reporting improvement and 19% reporting worsening. Blueberries and spinach were the foods most often reported to improve RA symptoms, while soda with sugar and desserts were those most often reported to worsen RA symptoms. Younger age and noting that sleep, warm room temperature, and vitamin/mineral supplements improve RA were each associated with reporting that foods affect RA symptoms. Medication use, sex, body mass index, smoking, disease duration, disease activity scores, and self-reported RA flares were not associated with reporting that foods affect RA. CONCLUSION: Nearly one-quarter of RA subjects with longstanding disease reported that diet had an effect on their RA symptoms. | |
| 28569176 | Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis. | 2017 May 31 | An increasing number of studies show how changes in intracellular metabolic pathways alter tumor and immune cell function. However, little information about metabolic changes in other cell types, including synovial fibroblasts, is available. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are the most common cell type at the pannus-cartilage junction and contribute to joint destruction through their production of cytokines, chemokines, and matrix-degrading molecules and by migrating and invading joint cartilage. In this review, we show that these cells differ from healthy synovial fibroblasts, not only in their marker expression, proto-oncogene expression, or their epigenetic changes, but also in their intracellular metabolism. These metabolic changes must occur due to the stressful microenvironment of inflamed tissues, where concentrations of crucial nutrients such as glucose, glutamine, and oxygen are spatially and temporally heterogeneous. In addition, these metabolic changes will increase metabolite exchange between fibroblast and other synovial cells, which can potentially be activated. Glucose and phospholipid metabolism as well as bioactive lipids, including sphingosine-1-phosphate and lysophosphatidic acid, among others, are involved in FLS activation. These metabolic changes likely contribute to FLS involvement in aspects of immune response initiation or abnormal immune responses and strongly contribute to joint destruction. | |
| 28378441 | Physical Activity to Reduce Fatigue in Rheumatoid Arthritis: A Randomized Controlled Trial | 2018 Jan | OBJECTIVE: Effective treatments for rheumatoid arthritis (RA) fatigue are limited. We tested the effect of a pedometer-based intervention on increasing physical activity and decreasing fatigue among individuals with RA. METHODS: Participants completed baseline questionnaires; had 1 week of activity monitoring; were randomized to control (education [EDUC]), pedometer and step-monitoring diary (PED), or pedometer and diary plus step targets (PED+) groups, and were followed for 21 weeks. At week 10, questionnaires were administered by phone to all participants. During the final week, all participants again had 1 week of activity monitoring. Primary outcomes were changes in average weekly steps and fatigue (Patient-Reported Outcomes Measurement Information System 7-item questionnaire) from baseline to week 21. Secondary outcomes were self-reported disease activity, physical function, pain interference, and depressive symptoms. Changes in steps were tested using a linear mixed model. Changes in fatigue were tested with repeated-measures models, including baseline, week-10, and week-21 scores. RESULTS: A total of 96 individuals participated. Eight did not complete the 21-week assessments. Both intervention groups significantly increased steps (+1,441 [P = 0.004] for PED and +1,656 [P = 0.001] for PED+), and the EDUC group decreased steps (-747 [P = 0.14]) (group-by-time interaction P = 0.0025). Between-group changes in fatigue were not significantly different (interaction P = 0.21). Mean changes in fatigue scores from baseline to week 21 were -1.6 (with-group P = 0.26), -3.2 (P = 0.02), and -4.8 (P = 0.0002) for EDUC, PED, and PED+ groups, respectively. Function and self-reported disease activity also improved in the PED and PED+ groups. CONCLUSION: Provision of pedometers, with and without providing step targets, was successful in increasing activity levels and decreasing fatigue in this sample of individuals with RA. | |
| 28833647 | Rheumatoid arthritis in review: Clinical, anatomical, cellular and molecular points of vie | 2018 Mar | Rheumatoid arthritis (RA) is the most common chronic autoimmune disease of the joints affecting close to 0.5-1.0% of the general population. Although the etiopathogenesis of RA remains elusive, the involvement of dendritic cells and type 17 T-helper cells appears to be pivotal in maintaining a state of chronic inflammation. RA is generally characterized by small joint involvement. A chronic inflammatory process leads to joint destruction and to tendon and ligament laxity and disintegration. These processes result in an imbalance of forces acting on the joints causing joint deformities including swan neck deformity, boutonniere deformity of the hands, flexion deformity of the wrist, lesser toe deformities, and others. In some instances, bony erosions subsequent to the RA disease process can result in life-threatening events including, for example, atlanto-axial subluxation, which can cause myelopathy and paralysis; and basilar invagination, which can cause brain stem injury and imminent death. Although less commonly involved, larger joints are not spared, as evidenced by the involvement of the elbow, hip, and shoulder joints in a sizable proportion of RA patients. The progression and prognosis of this disease entity are variable, guarded and dependent on the efficacy and response to treatment modalities employed. Inadequate management results in disease progression, which ultimately leads to joint erosion, destruction, deformities and substantial decrease in the functional quality of life. Clin. Anat. 31:216-223, 2018. © 2017 Wiley Periodicals, Inc. | |
| 28281906 | PAD4: pathophysiology, current therapeutics and future perspective in rheumatoid arthritis | 2017 Apr | Peptidyl arginine deiminase 4 (PAD4) is an enzyme that plays an important role in gene expression, turning out genetic code into functional products in the body. It is involved in a key post translational modification, which involves the conversion of arginine to citrulline. It regulates various processes such as apoptosis, innate immunity and pluripotency, while its dysregulation has a great impact on the genesis of various diseases. Over the last few years PAD4 has emerged as a potential therapeutic target for the treatment of rheumatoid arthritis (RA). Areas covered: In this review, we discuss the basic structure and function of PAD4, along with the role of altered PAD4 activity in the onset of RA and other maladies. We also elucidate the role of PAD4 variants in etiology of RA among several ethnic groups and the current pre-clinical inhibitors to regulate PAD4. Expert opinion: Citrullination has a crucial role in RA and several other disorders. Since PAD4 is an initiator of the citrullination, it is an important therapeutic target for inflammatory diseases. Therefore, an in depth knowledge of the roles and activity of PAD4 is required to explore more effective ways to conquer PAD4 related ailments, especially RA. | |
| 26297177 | IL-20 in rheumatoid arthritis. | 2017 Jun | Rheumatoid arthritis, a systemic autoimmune disease, causes chronic joint inflammation and bone destruction. Interleukin (IL)-20's association with this disease, and its expression and regulation has been extensively studied since 2006. Anti-IL-20 antibody has paved the way to clinical trials aimed at blocking the pathogenic actions of IL-20 in rheumatoid arthritis. This review focuses on current knowledge of IL-20's involvement in the pathogenesis of rheumatoid arthritis. | |
| 29424183 | [Progress on rheumatoid arthritis in elderly]. | 2017 Jun 25 | During choosing non-steroidal anti-inflammatory drugs(NSAIDs), risk factors should be evaluated in elder patients with rheumatoid arthritis. The present study focused on biological therapies, and elderly patients should be more concerned about the risk of infection when used it. Traditional Chinese medicine has advantages of obvious curative effect, especially for tripterygium wilfordii, large clinical trial on western and Chinese medical accurate drug strategies for old patients with rheumatoid arthritis. Old patients are easier to suffer from cardiac diseases and interstitial lung disease, rheumatoid arthritis could be controlled along with the treatment for coexistent disease. The incidence of rheumatoid arthritis in old patients is the same with other RA, and need to treat to target based on the aim of relieve pain and reduce activity of diseases, while the clinical charteristic and treatment target in elder patients with rheumatoid arthritis were not similar with other aged patient, so treatment standard target would vary with aging. Resent clinical studies excluded old patients, lead to lack of evidence-based medicine data. Clinical study for elder patients with rheumatoid arthritis are energetically carrying out, and could provide base and guide for clinical treatment. | |
| 28330532 | [Rheumatoid arthritis and hand surgery]. | 2017 Mar 13 | Rheumatoid arthritis results in characteristic deformities of the hand. Medical treatment has undergone a remarkable development. However, not all patients achieve remission or tolerate the treatment. Patients who suffer from deformities and persistent synovitis may be candidates for hand surgery, for which the main goals are pain relief and improved function. Surgical interventions can be divided into prophylactic and therapeutic procedures. The treatment strategy is individual and depends on close collaboration between rheumatologists, hand surgeons and patients. | |
| 28257989 | Nanotherapeutics relieve rheumatoid arthritis. | 2017 Apr 28 | Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease associated with persistent multiarticular synovitis, cartilage destruction, and even loss of joint function. Although remarkable progress has been made in the clinical treatment of RA, long-term administration of anti-rheumatic drugs still suffers quite a few drawbacks, including high dose and high frequency of drug use, as well as dysfunction of the heart, liver, kidney, and so forth. For the above problems, nanotherapeutic agents are developed to avert non-specific binding and upregulate the efficacy by improving the accumulation of drugs in lesion tissues. In this article, some of the most frequently used anti-RA agents were summarized, and the recent treatment of RA with passive or active targeting nanotheranostics was systematically illustrated. In addition, the prospect of nanovehicles in clinical therapy of RA was discussed and predicted. | |
| 28752373 | Skin Manifestations of Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, and Spondyloar | 2017 Dec | Extra-articular manifestations of rheumatoid arthritis, juvenile idiopathic arthritis, and various spondyloarthritides including psoriatic arthritis, ankylosing spondylitis, reactive arthritis, and inflammatory bowel disease-associated spondyloarthritis often involve the skin and may occur before or after diagnosis of these rheumatic diseases. Cutaneous manifestations encompass a wide range of reactions that may have a notable negative impact not only on the physical but especially on the emotional and psychosocial well-being of these patients. Several cutaneous manifestations have been related to rheumatoid arthritis such as subcutaneous nodules including classical rheumatoid nodules, accelerated rheumatoid nodulosis, and rheumatoid nodulosis; vascular disorders like rheumatoid vasculitis, livedo racemosa, and Raynaud's phenomenon; and neutrophilic and/or granulomatous diseases like pyoderma gangrenosum, Sweet's syndrome, rheumatoid neutrophilic dermatitis, interstitial granulomatous dermatitis with arthritis, as well as palisaded neutrophilic and granulomatous dermatitis. In juvenile idiopathic arthritis, the main cutaneous manifestations include an evanescent rash, rheumatoid nodules, as well as plaque and guttate psoriasis. Plaque psoriasis is also the main skin disease involved in spondyloarthritides. Furthermore, other forms of psoriasis including guttate, inverse, erythrodermic, pustular, and particularly nail psoriasis may also occur. In addition, a variety of drug-induced skin reactions may also appear in these diseases. Early recognition and understanding of these different dermatologic manifestations together with an interdisciplinary approach are often needed to optimize management of these diseases. | |
| 28493174 | Genomics, transcriptomics and proteomics to elucidate the pathogenesis of rheumatoid arthr | 2017 Aug | Rheumatoid arthritis is an autoimmune disease that affects several organs and tissues, predominantly the synovial joints. The pathogenesis of this disease is not completely understood, which maybe involved in the genomic variations, gene expression, protein translation and post-translational modifications. These system variations in genomics, transcriptomics and proteomics are dynamic in nature and their crosstalk is overwhelmingly complex, thus analyzing them separately may not be very informative. However, various '-omics' techniques developed in recent years have opened up new possibilities for clarifying disease pathways and thereby facilitating early diagnosis and specific therapies. This review examines how recent advances in the fields of genomics, transcriptomics and proteomics have contributed to our understanding of rheumatoid arthritis. | |
| 28918917 | Leukocytapheresis in rheumatoid arthritis. | 2017 Oct | In this article, we discussed leukocytapheresis (LCAP) for rheumatoid arthritis (RA). Recently, a simple and practical on-line continuous LACP system has been developed. It is equipped with a direct hemoperfusion column (Cellsorba(®), Asahikasei Medical Co., Ltd.) packed with fine-diameter polyester fibers, which are commonly used to adsorb white blood cells to prevent a graft-versus-host reaction during blood transfusion. Clinical trials revealed that LCAP is a effective and safe therapy for patients with drug-resistant RA or RA complicated with vasculitis. Because the procedure is simple and requires no plasma substitutes and the volume needed for extracorporeal circulation is less than that for other plasmapheresis, LCAP might be accepted as an optional therapeutic modality for active RA that was refractory to conventional drug therapy including biological agents. The mechanism of the efficiency of LCAP on RA is unclear. LCAP may cause a reduction of activated T cells from affected joints, down-regulation of Pgp on helper T cells and restoration of Treg function, and that may modify the abnormal cytokine balance. These findings may explain some of the mechanisms by which the articular symptoms are improved by LCAP. | |
| 27484962 | Fractalkine/CX3CL1 in rheumatoid arthritis. | 2017 May | Fractalkine is a CX3C chemokine that exists in both membrane-bound and soluble forms. Interaction between fractalkine and its unique receptor (CX3CR1) induces cell adhesion, chemotaxis, crawling, "accessory cell" activity, and survival. The serum level of fractalkine is elevated in patients with rheumatoid arthritis (RA) and is correlated with disease activity. Peripheral blood CD16(+  )monocytes and a subset of T cells express CX3CR1, while fractalkine is expressed on fibroblast-like synoviocytes and endothelial cells in the synovial tissue of patients with RA. Fractalkine expression is enhanced by tumor necrosis factor-α and interferon-γ, and it promotes the migration of monocytes, T cells, and osteoclast precursors into RA synovial tissue. Fractalkine also induces the production of inflammatory mediators by macrophages, T cells, and fibroblast-like synoviocytes. Moreover, fractalkine promotes angiogenesis and osteoclastogenesis. In an animal model of RA, arthritis was improved by the abrogation of fractalkine. Recently, a clinical trial of an anti-fractalkine monoclonal antibody for the treatment of RA commenced in Japan. We review the multiple roles of fractalkine in the pathogenesis of RA and its potential as a therapeutic target for this disease. | |
| 28400099 | Quality of life and functional capacity in patients with rheumatoid arthritis - Cross-sect | 2018 Nov | OBJECTIVES: To analyze the Health related Quality of Life (HRQoL) and physical function in rheumatoid arthritis (RA) patients and compare it with the general population. We also intended to analyze about disease activity influence in HRQoL and functional capacity, as well as determine potential determinants for these outcomes. MATERIAL AND METHODS: A cross-sectional study was conducted in RA patients from a university hospital of Portugal. We obtained Short Form 36, EuroQoL 5D, health assessment questionnaire, visual analog scale for pain and patient's assessment of disease activity. Comparisons between SF-36 and EQ-5D values with our population reference values were conducted using the Mann-Whitney test. Data were compared in different levels of disease activity, using Kruskal Wallis test and Fisher's exact test. A multiple regression analysis was conducted to identify the potential determinants of outcomes. RESULTS: RA sample showed significantly lower values than the portuguese general population on physical summary measure of SF-36 (median=32 vs. 50, p<0.001) and EQ-5D (median=0.620 vs. 0.758 respectively; p<0.001). Lower disease activity levels had better PROs and this was true even when compared patients achieving remission with those in low disease activity. The HAQ (r(2)=67%), VAS-P (r(2)=62%) and VAS-DA (r(2)=58%) were the variables that strongly related to SF-36. Considering HAQ, the strongest relation was found with VAS-P, VAS-DA and age (r(2)=60%, 61% and 33%, respectively). Multiple regression analysis identified HAQ, VAS-P and educational status as determinants of the HRQoL; age, female gender, employment, VAS-P and VAS-DA as determinants of physical function. CONCLUSION: Impairment of HRQoL in RA patients is enormous. We found significant differences between different levels of disease activity, showing higher HRQoL and functional capacity at lower disease activity levels. | |
| 28349194 | Arthritis models: usefulness and interpretation. | 2017 Jun | Animal models of arthritis are used to better understand pathophysiology of a disease or to seek potential therapeutic targets or strategies. Focusing on models currently used for studying rheumatoid arthritis, we show here in which extent models were invaluable to enlighten different mechanisms such as the role of innate immunity, T and B cells, vessels, or microbiota. Moreover, models were the starting point of in vivo application of cytokine-blocking strategies such as anti-TNF or anti-IL-6 treatments. The most popular models are the different types of collagen-induced arthritis and arthritis in KBN mice. As spontaneous arthritides, human TNF-α transgenic mice are a reliable model. It is mandatory to use animal models in the respect of ethical procedure, particularly regarding the number of animals and the control of pain. Moreover, design of experiments should be of the highest level, animal models of arthritis being dedicated to exploration of well-based novelties, and never used for confirmation or replication of already proven concepts. The best interpretations of data in animal models of arthritis suppose integrated research, including translational studies from animals to humans. |