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

ID PMID Title PublicationDate abstract
27125255 Safety of anti-rheumatic drugs for rheumatoid arthritis in pregnancy and lactation. 2016 Sep Women with rheumatoid arthritis (RA) are often of childbearing age and therefore questions regarding reproductive health and the use of medications, including disease-modifying anti-rheumatic drugs (DMARDs) may arise during the clinical consultation. Each patient requires individual assessment in order to effectively manage the disease while minimizing any treatment-associated risks to the fetus. Although good-quality controlled trials are lacking, there is an increasing volume of evidence surrounding the use of immunosuppressive therapies in pregnancy and lactation. This review summarizes the currently available information which can be of benefit to clinicians guiding patients and their families through the risks and benefits of continuing RA therapy during pregnancy and lactation. Further studies and ongoing surveillance of drug safety in pregnancy are required to resolve the uncertainties that remain regarding synthetic and biologic DMARDs.
27050563 Diagnostic accuracy of anti-RA33 antibody for rheumatoid arthritis: systematic review and 2016 May OBJECTIVES: The main purpose of this meta-analysis is to evaluate the diagnostic value of anti-RA33 antibody for rheumatoid arthritis. METHODS: In order to obtain eligible studies, a systematic literature search was performed on PubMed, Web of science, EBSCO, CNKI and CBM from January 2000 to September 2015. Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was employed to assess the quality of the relevant studies. Meta-disc 1.4 and Stata 11.0 were adopted in this meta-analysis. RESULTS: After rigorous review, fifty studies were included in this study, which are all reliable to summarise the diagnostic value in this meta-analysis. The result of the analysis shows the pooled sensitivity is 0.33 (95% confidence interval (CI): 0.31-0.34) and the specificity is 0.90 (95% CI: 0.89-0.90), for the diagnosis of rheumatoid arthritis. Besides, the area under the summary ROC curve (AUC) is 0.6863. CONCLUSIONS: The current evidence suggests that anti-RA33 antibody has high diagnostic specificity value for rheumatoid arthritis, which may be useful for the disease diagnostic application. To verify this conclusion, more prospective research on the diagnostic value of anti-RA33 antibody for rheumatoid arthritis are needed in the future.
26215034 Immunogenetics of rheumatoid arthritis: Understanding functional implications. 2015 Nov The last decade has seen a dramatic technological revolution. The characterisation of the majority of the common variations in our genetic code in 2003 precipitated the discovery of the genetic risk factors predisposing to Rheumatoid Arthritis development and progression. Prior to 2007, only a handful of genetic risk factors had been identified, HLA, PTPN22 and CTLA4. Since then, over 100 genetic risk loci have been described, with the prediction that an ever-increasing number of risk alleles with consistently decreasing effect sizes will be discovered in the years to come. Each risk locus harbours multiple candidate genes and the proof of causality of each of these candidates is as yet unknown. An enrichment of these RA-associated genes is found in three pathways: T-cell receptor signalling, JAK-STAT signalling and the NF-κB signalling cascade, and currently drugs targeting these pathways are available for the treatment of RA. However, the role that RA-associated genes have in these pathways and how they contribute to disease is not always clear. Major efforts in understanding the contribution of genetic risk factors are currently under way with studies querying the role of genetic variation in gene expression of coding and non-coding genes, epigenetic marks and other regulatory mechanisms yielding ever more valuable insights into mechanisms of disease. Recent work has suggested a possible enrichment of non-coding RNAs as well as super-enhancers in RA genetic loci indicating possible new insights into disease mechanism. This review brings together these emerging genetic data with an emphasis on the immunogenetic links these findings have provided and what we expect the future will bring.
26227165 Rheumatoid arthritis in Latin America: challenges and solutions to improve its diagnosis a 2015 Mar Rheumatoid arthritis (RA) is a disease with multiple clinical manifestations and chronic complications that requires a multidisciplinary team to treat and monitor patients. This understanding between the different medical and health professionals is essential in obtaining patient well-being. This is the reason behind the assessment of the difficulties and limitations seen in Latin America in the field of rheumatology. The aim is to suggest possible mechanisms and solutions to strengthen the knowledge and understanding of the way the disease behaves and how it can be handled by doctors and medical professionals.
26239386 Potential Therapy for Rheumatoid Arthritis and Sjögren Syndrome With Human Chorionic Gona 2016 May Autoimmune diseases such as rheumatoid arthritis (RA) and Sjögren syndrome (SS) ameliorate during pregnancy, through dampening (immunotolerance) of the maternal immune system which protects the fetus from rejection. A large number of studies have shown that human chorionic gonadotropin (hCG) contributes to this tolerance. Studies on animal models have reaffirmed that hCG treatment mimics the benefits of pregnancy. Based on the scientific evidence, randomized clinical trials comparing hCG with current therapies and/or placebo are recommended for RA, SS, and for other autoimmune diseases such as, type 1 diabetes and ankylosing spondylitis, which also get better during pregnancy and hCG treatment seems to help.
26374913 Towards prevention of autoantibody-positive rheumatoid arthritis: from lifestyle modificat 2016 Apr Recent advances in research into the earliest phases of RA have provided additional insights into the processes leading from the healthy to the diseased state. These insights have opened the way for the development of preventive strategies for RA, which represents a significant paradigm shift from treatment to prevention and will have major implications for patients as well as society. It would be a huge step forward if clinical signs and symptoms, disability, impaired quality of life and the need for chronic immunosuppressive treatment could be prevented. RA can be seen as a prototypic autoimmune disease, and discoveries about the preclinical diseased state for RA could potentially facilitate research into prevention of other immune-mediated inflammatory diseases such as type 1 diabetes, SLE and multiple sclerosis. This review focuses on the current knowledge of factors contributing to the development of RA and discusses the opportunities for intervention.
27098907 Family history of rheumatoid arthritis: an old concept with new developments. 2016 Jun Family history of rheumatoid arthritis (RA) is a proxy for an individual's genetic and, in part, environmental risk of developing RA, and is a well-recognized predictor of disease onset. Although family history of RA is an old concept, the degree of familial aggregation of RA, whether it differs by age, sex, or serology, and what value it has for clinical decisions once a diagnosis of RA has been made remain unclear. New data have been emerging in parallel to substantial progress made in genetic association studies. In this Review, we describe the various ways that familial aggregation has been measured, and how the findings from these studies, whether they are based on twins, cohorts of first-degree relatives, or genetic data, correspond to each other and aid understanding of the aetiology of RA. In addition, we review the potential usefulness of family history of RA from a clinical point of view, demonstrating that, in the era of big data and genomics, family history still has a role in directing clinical decision-making and research.
26160492 Subcutaneous abatacept in rheumatoid arthritis: current update. 2015 INTRODUCTION: A number of biologic agents have been approved for the treatment of rheumatoid arthritis (RA). They have changed the landscape of therapy and demonstrate substantial efficacy with a good safety record. One of these agents is intravenous (i.v.) abatacept (ABA), which has a novel mechanism of action by selectively inhibiting the interaction between T- and antigen-presenting cells. Recently, ABA administered by subcutaneous (s.c.) injection has also been approved for use in RA. In this review, will focus in recent data published in this agent. AREAS COVERED: This paper reviews Phase III clinical trials (ACQUIRE, ACCOMPANY, ALLOW, ATTUNE, AMPLE and AVERT) in terms of clinical efficacy including long-term efficacy, radiographic progression, safety and immunogenicity. EXPERT OPINION: Given the current trend in biologic therapy to s.c. administration, the availability of both i.v. and s.c. ABA provides considerable advantage both to patients and physicians in this competitive environment. The clinical trials have shown comparable efficacy and safety of s.c. ABA to i.v. ABA and others biologics.
25819216 Management of neutropenia in patients with rheumatoid arthritis. 2015 Jul Neutropenia is defined as a neutrophil count lower than 1.5g/L, with categorization as mild, moderate, or severe when the count is 1.5-1g/L, 1-0.5g/L, or<0.5g/L, respectively. The main complication is infection, whose risk increases with the depth and duration of the neutropenia. Comprehensive etiological investigations are mandatory to determine the best treatment strategy. Constitutional neutropenia is rarely seen in everyday rheumatology practice. It predominantly affects patients of African descent and is usually moderate and well tolerated. Congenital neutropenia due to genetic abnormalities is severe and chiefly seen in the pediatric population. Most cases of neutropenia in patients with rheumatoid arthritis (RA) are acquired. Medications are the most common causes, making detailed history-taking crucial. Many medications used to treat RA can induce neutropenia. Folic acid deficiency should be sought routinely in patients taking methotrexate. A less common cause of neutropenia is an RA-related autoimmune reaction. Splenomegaly suggests Felty's syndrome, which is accompanied with large granular lymphocytic (LGL) leukemia in 40% of cases. The treatment depends on the depth of the neutropenia and findings from the etiological workup. A neutrophil count below 0.5g/L, a fever, and the presence of clinical signs indicate a life-threatening condition requiring emergent treatment. In other patients, the first step is immediate discontinuation of any possibly involved drugs, simultaneously with the etiological workup.
25163744 Role of synovial fibroblasts in rheumatoid arthritis. 2015 Rheumatoid arthritis (RA) is the most common autoimmune articular disorder. It is characterized by chronic inflammation and progressive joint destruction. As research traditionally focused on immune cells and cytokines, the role of stromal cells was addressed only to a limited extent. However, cell-cell interactions within the rheumatoid synovium alter the phenotype of synovial fibroblasts (SFs), which are nowadays considered as active and aggressive drivers in the destructive process of RA. SFs actively attach to and invade articular cartilage, thereby expressing increased amounts of adhesion molecules and proinflammatory and matrix-degrading mediators. Furthermore, RASFs stimulate synovial vascularization through the release of proangiogenic factors. As a result, angiogenesis supports the influx of immune cells into affected joints, thereby perpetuating inflammatory processes, and facilitates access of RASFs to the bloodstream, thus boosting dissemination of RA. Despite intensive research, early pathophysiological processes still remain largely unknown. In this respect, a prearthritic phase of RA is discussed. Early and intensive therapy is considered to be very effective and beneficial for long-term outcome. However, although innovative therapy and improved treatment strategies are applied to achieve clinical remission, failure of or only partial response to therapy remains common. Given that none of the currently approved therapies target RASFs, intensive research into new strategies is warranted. In this review, novel findings leading to the altered fibroblast phenotype in RA are discussed in terms of progressive inflammation and destruction. Potential novel therapeutic concepts are also addressed.
25163742 Biomarkers for radiographic progression in rheumatoid arthritis. 2015 Treatment of patients with rheumatoid arthritis (RA) is rarely personalized, since predictors of disease course are lacking. The severity of RA can be measured objectively by radiographic progression. The most reliable way to measure radiographic progression is in a longitudinal cohort with serial time points, scoring on a quantitative scale, with a validated scoring method and trained readers. Current models used to predict radiographic progression are based on C-reactive protein and anti-citrullinated protein antibodies. Other biomarkers could increase the prognostic ability of these models. In this review, we evaluated the published (and partly nonpublished) data on genetic, serologic, and imaging biomarkers for the severity of joint destruction in RA. We evaluated variants in 10 genes (CD40, IL2RA, IL4R, IL15, OPG, DKK1, SOST, GRZB, MMP9, and SPAG16). In 5 variants (IL2RA, DKK1, GRZB, MMP9, and SPAG16), we found evidence of an association at the functional level. We evaluated several serological biomarkers, namely, autoantibodies (RF, ACPA, anti-CarP), markers related to inflammation (ESR, CRP), and proteinases or components of the extracellular matrix of bone and cartilage (MMP3, CTX-I, CTX-II, COMP, TIMP1, PYD, RANKL/OPG, CXCL13). Finally, we evaluated markers that can be visualized by ultrasound or MRI, including erosions, bone marrow edema, synovitis, and tenosynovitis. Several studies showed that bone marrow edema and synovitis on MRI are robust predictors of radiographic progression. Some studies showed that inflammation detected with ultrasound predicted radiographic progression. Future studies will reveal whether adding and combining all these different biomarkers will increase the accuracy of risk models predicting radiographic progression in RA.
27412376 Meta-analyses of the association of HLA-DRB1 alleles with rheumatoid arthritis among Arabs 2017 Jul AIM: Various studies incorporating Arab populations have reported on specific associations between HLA-DRB1 variants and rheumatoid arthritis (RA). We sought to provide an overview on the association of HLA-DRB1 with RA in Arabs using meta-analysis tools. METHODS: Data on allele counts and frequencies were compiled from the relevant literature (published before 16 February 2016) and the associations of 13 -DRB1 variants with RA were assessed; relationships were defined in terms of odds ratios (ORs) with a 95% confidence interval. RESULTS: Based on a collection of six studies, risk conferring or protective allele associations were derived from allele counts in 475 RA patients and 1213 controls. Two HLA-DRB1 alleles (-DRB1*04, *10) significantly conferred an increased risk for RA (OR > 2; P < 0.0001). Conversely, four alleles (-DRB1*03, *07, *11 and *13) significantly conferred a protective effect against RA (OR < 1; P < 0.05). No significant associations with RA were found for seven -DRB1 variants (-DRB1*01, *08, *09, *12, *14, *15 and *16). CONCLUSION: With increased statistical power and effect size over individual studies, we present a more robust profile on the association of HLA-DRB1 variants with RA in the Arab ethnicity, and contribute to the global geo-ethnic picture in this context.
25876749 Cardiovascular effects of methotrexate in rheumatoid arthritis revisited. 2015 Cardiovascular events such as myocardial infarction (MI) and stroke due to enhanced inflammatory atherosclerosis account for increased premature mortality in rheumatoid arthritis (RA). Accumulated evidence suggests that accelerated atherosclerosis and related cardiovascular comorbidities in RA are confounded not only by traditional risk factors (TRF) but also by a number of immune and inflammatory pathways. Since chronic inflammation and autoimmune disorders play a key role in atherosclerosis and related cardiovascular complications in RA, effective suppression of systemic inflammation can be viewed as a strategy for cardiovascular therapy and prevention in this disease. This article overviews some mechanisms of action of methotrexate on TRF, clinical and subclinical manifestations of RA-induced atherosclerosis, and related cardiovascular morbidity and mortality.
26379192 The interplay between inflammation and metabolism in rheumatoid arthritis. 2015 Sep 17 Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone that lead to joint destruction. The autoimmune process in RA depends on the activation of immune cells, which use intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. An intricate cytokine network participates in inflammation and in perpetuation of disease by positive feedback loops promoting systemic disorder. The widespread systemic effects mediated by pro-inflammatory cytokines in RA impact on metabolism and in particular in lymphocyte metabolism. Moreover, RA pathobiology seems to share some common pathways with atherosclerosis, including endothelial dysfunction that is related to underlying chronic inflammation. The extent of the metabolic changes and the types of metabolites seen may be good markers of cytokine-mediated inflammatory processes in RA. Altered metabolic fingerprints may be useful in predicting the development of RA in patients with early arthritis as well as in the evaluation of the treatment response. Evidence supports the role of metabolomic analysis as a novel and nontargeted approach for identifying potential biomarkers and for improving the clinical and therapeutical management of patients with chronic inflammatory diseases. Here, we review the metabolic changes occurring in the pathogenesis of RA as well as the implication of the metabolic features in the treatment response.
25302847 Angiotensin II in inflammation, immunity and rheumatoid arthritis. 2015 Feb Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that is characterized by increased cardiovascular morbidity and mortality, independent of the traditional risk factors for cardiovascular disease. Although classically known for its role in the regulation of circulatory homeostasis, angiotensin II (Ang II) is recognized to act as a powerful proinflammatory mediator. Some research has showed that Ang II plays important roles in autoimmune diseases, including RA, systemic lupus erythematosus and multiple sclerosis. Ang II blockers prove effective in reducing inflammation and autoimmunity in rheumatic diseases and their relative safety, together with their effects for reducing the cardiovascular disease risk, suggest that Ang II blockers may at least act as effective adjunctive therapy for disease control in patients with RA. The present review focuses systematically on the potential impact of Ang II and its receptors on inflammation and immunomodulation in patients with RA.
26164649 MicroRNAs in rheumatoid arthritis: altered expression and diagnostic potential. 2015 Nov Rheumatoid arthritis (RA) is a polygenic disease characterized by autoimmunity and systemic inflammation with progressive impairment of joints that results in lifelong disability and increased mortality. Early diagnosis and therapeutic intervention or treatment can prevent severe disease manifestations in patients suffering from RA. The use of appropriate predictive biomarkers may improve the efficiency of RA therapy. The general aim of this review is to highlight the most recent findings on miRNAs expression profiles in RA patients and to discuss their potential as new biomarkers for diagnostic purposes. The current literature demonstrates that a variety of miRNAs is frequently dysregulated in RA patients. To date, the majority of miRNAs have been found to be overexpressed during the natural course of RA. MiR-16, miR-146a/b, miR-150, miR-155, and miR-223 described here were shown to be overexpressed at the systemic level: in both the periphery and RA joints. Circulating peripheral blood miRNAs, especially miR-16, miR-21, miR-24, miR-26a, miR-125a-5p, miR-125b, miR-126-3p, miR-223, and miR-451, which are elevated in the plasma or serum, are considered to be the most promising non-invasive biomarkers for the detection of RA.
27457285 Therapeutic potential of cysteine-rich protein 61 in rheumatoid arthritis. 2016 Oct 30 Cysteine-rich protein 61 (Cyr61)/CCN1, a product of an immediate early gene, can directly accommodate cell adhesion and migratory processes whilst simultaneously regulating the production of other cytokines and chemokines through paracrine and autocrine feedback loops. This intricate functionality of Cyr61 indicate its important role in targeting components of the infectious or chronic inflammatory disease processes including rheumatoid arthritis (RA). Recent work has focused on the role of Cyr61 in RA. For example, Cyr61 induced proIL-1β production in FLS via the AKT-dependent NF-κB signaling pathway. Moreover, Cyr61-siRNA decreased the levels of matrix metalloproteinase (MMP)-3 and MMP-13, and induced apoptosis in RA-FLS cells. These results indicated that Cyr61 may represent a novel target for the treatment of RA. In this article we will introduce the molecular properties of Cyr61, discuss the function of Cyr61, and the therapeutic potential of modulating the Cyr61 in RA.
27052277 Pathogenic role of platelets in rheumatoid arthritis and systemic autoimmune diseases. Per 2016 Apr Well-recognized for their role in vascular homoeostasis, platelets may play a major role in inflammation and immunomodulation. Substantial data are emerging on the pathogenic involvement of platelets in inflammatory arthritis and autoimmune diseases, indicating the existence of crosstalk between the coagulation and inflammation system. Upon activation, platelets release pro-inflammatory platelets microparticles, which interact with leucocytes leading to joint and systemic inflammation in rheumatoid arthritis. Platelets activation by immune complexes activate dendritic cells promoting the secretion of interferon alpha, which has a key role in the development of systemic lupus erythematous. In this review, we discuss the current data on the role of platelets in the pathophysiology of inflammatory arthritis and various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis.
25227591 Circadian use of glucocorticoids in rheumatoid arthritis. 2015 A clear temporal relationship exists in rheumatoid arthritis (RA) patients between increased nocturnal levels of pro-inflammatory cytokines, such as TNF-α and interleukin (IL)-6, pro-inflammatory hormones (i.e. melatonin, prolactin) and insufficient night production of the anti-inflammatory cortisol (circadian rhythm). Under long-standing chronic stress of disease, insufficient cortisol is available to inhibit an ongoing nocturnal immune/inflammatory reaction. Clinical RA symptoms follow the same circadian rhythm with highest morning severity. Chronotherapy with nighttime glucocorticoid (GC) availability optimizes the treatment of RA patients with low-dose GCs through more efficient targeting of mediators of the immune/inflammatory reaction during the night to be available on arising. Circadian use of low-dose, long-term prednisone, by using night-release formulations (ingested at 10 to 11 p.m.) especially in early RA patients, appears characterized by a significantly superior efficacy on decreasing morning stiffness and IL-6 serum levels, compared to conventional daytime immediate-release prednisone. Shift from medium-dose, immediate-release prednisone (over 7.5-10 mg/day) to night-release formulations GC low-dose, long-term chronotherapy requires a gradual passage, since the hypothalamic-pituitary-adrenal axis of the treated RA patients, potentially altered by a negative feedback induced by the medium/high daily exogenous GC administration, needs time to re-synchronize control of endogenous GC production into a circadian and more physiological nocturnal hormone availability/optimized efficacy.
26210510 Lipid and Metabolic Changes in Rheumatoid Arthritis. 2015 Sep While the most obvious manifestations of rheumatoid arthritis (RA) involve inflammation and damage in the synovial joints, the systemic effects of the condition are widespread and life-threatening. Of particular interest is the 'lipid paradox' of RA, where patients with a numerically equivocal starting lipid profile have a significantly raised risk of cardiovascular (CV) events and response to therapy results in a 'normalization' of lipid levels and reduction in events. Changes in lipids can be seen before overt disease manifestations which suggest that they are closely linked to the more widespread inflammation-driven metabolic changes associated with tumour necrosis factor (TNF). Cachexia involves a shift in body mass from muscle to fat, which may or may not directly increase the cardiovascular risk. However, since TNF inhibition is associated with reduction in cardiovascular events, it does suggest that these widespread metabolic changes involving lipids are of importance. Analysis of single lipids or metabolites have been used to identify some of the key changes, but more recently, metabolomic and lipidomic approaches have been applied to identify a broad spectrum of small molecule changes and identify potentially altered metabolic pathways. Further work is needed to understand fully the metabolic changes in lipid profiles and identify novel ways of targeting desired profile changes, but work so far does suggest that a better understanding may allow management of patients to downregulate the systemic effects of their disease that puts them at risk of cardiovascular complications.