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ID PMID Title PublicationDate abstract
30605055 The Role of Extracellular Nucleic Acids in Rheumatoid Arthritis. 2018 Chronic inflammation, synovial hyperplasia, and local hypoxia lead to synovial cell activation causing severe joint damage in chronic-inflammatory rheumatoid arthritis (RA). The proinflammatory and joint-destructive property of the increased release of extracellular nucleic acids has been demonstrated for extracellular mitochondrial DNA and oxidized DNA using an arthritis model. Microparticles derived from different cells are able to transport nucleic acids to distant cells and promote cellular activation in RA. In addition, extracellular RNA (eRNA) is present in the RA synovial lining layer, whereas eDNA could be detected in various areas of synovial tissue when compared to controls. The main source of eDNA is the formation of neutrophil extracellular traps (NETs) due to increased amounts of activated neutrophils in the synovial fluid in RA. A central cell type of joint destruction is the activated RA synovial fibroblast (RASF) characterized by increased production of proinflammatory factors, matrix-degrading enzymes, enhanced matrix adhesion, and cell migration. eRNA was shown to be released by RASF under hypoxia and RNase activity was increased in RA synovial fluid. In vitro, RNase-mediated reduction of eRNA decreased RASF adhesion to cartilage but not proliferation or adhesion to endothelial cells. In vivo, RNase1 treatment reduced RASF invasion into cartilage. Therefore, extracellular nucleic acids induced by (auto)immune responses in RA appear to promote inflammation and local joint destruction.
28398519 Sedentary behaviour in rheumatoid arthritis: definition, measurement and implications for 2018 Feb 1 RA is a chronic autoimmune disease characterized by high grade-inflammation, and associated with elevated cardiovascular risk, rheumatoid-cachexia and functional impairment. Sedentary behaviour (SB) is linked to heightened inflammation, and is highly pervasive in RA, likely as a result of compromised physical function and persistent fatigue. This high sedentarity may exacerbate the inflammatory process in RA, and hold relevance for disease-related outcomes. The aim of this narrative review is to provide an overview of the definition, measurement and health relevance of SB in the context of RA. Contradictions are highlighted with regard to the manner in which SB is operationalized, and the significance of SB for disease outcomes in RA is outlined. The advantages and disadvantages of SB measurement approaches are also discussed. Against this background, we summarize studies that have reported SB and its health correlates in RA, and propose directions for future research.
30022679 14-3-3η protein: a promising biomarker for rheumatoid arthritis. 2018 Aug Effective management of rheumatoid arthritis (RA) depends on early identification followed by timely invention and proper monitoring of treatment responses which remain challenges facing rheumatologists for lacking biomarkers of high sensitivity and specificity. 14-3-3η has been reported to be a novel RA-related biomarker inducing the expression of multiple factors mediating the pathogenesis of RA, and increasing the diagnostic capture when combined with rheumatoid factor and anticyclic citrullinated peptide antibody. Besides, elevated serum 14-3-3η was relevant to more serious joint erosion and worse therapy outcomes. Here, we summarized the emerging knowledge regarding the roles 14-3-3η plays in RA and its clinical implications as diagnostic, prognostic and therapeutic response surrogate as well as potential drug target for RA.
30556738 Measuring disease activity and response to treatment in rheumatoid arthritis. 2019 Feb Introduction: Effective treatment of rheumatoid arthritis (RA) requires suppression of the underlying inflammation. Measurement of such inflammation, the disease activity, is mandatory to target treatment and maximize outcomes. However, this is not as straightforward as it may seem. Areas covered: The many tools developed to measure disease activity in RA, from composite scores and patient-reported outcomes, to laboratory markers and imaging are discussed, with a focus on their utility in guiding therapy and assessing response. The complex issues in measuring disease activity in RA, whether in clinical trials or normal clinical practice, and in the context of national guidelines and recommendations, available time, and resources are considered. Expert commentary: The key to effective management of RA is the rapid suppression of inflammation, ideally to remission, with maintenance of such remission. The aim is to prevent disability and maximize quality of life. Central to this is the ability to determine disease activity (potentially open to suppression) as opposed to damage (irreversible). A variety of measures are currently available, allowing better assessment of response to treatment. In the future, the development of predictive biomarkers allowing targeting of drugs may revolutionize this field and render the tools of today redundant.
29512949 [Viral arthritis]. 2018 Mar 7 Arthritis and arthralgia during a viral infection are often polyarticular and symmetric and can mimic rheumatoid arthritis. Depending on germs, others signs and symptoms as fever, cutaneous rash (Parvovirus B19) or jaundice (hepatitis) can be present. Worldwide most common germs are Parvovirus B19, hepatitis B and C, HIV and alphavirus. There are significant differences throughout the world and epidemiology continues to evolve with a progression of vector-borne infections. Diagnosis of viral arthritis is often difficult and is based on epidemiological, clinical and serological data.
30002215 Neutropaenia and splenomegaly without arthritis: think rheumatoid arthritis. 2018 Jul 11 Felty syndrome(FS) is an uncommon, but severe, extra-articular manifestation of rheumatoid arthritis (RA). It occurs in patients with longstanding RA. It is extremely rare for RA to present as FS or develop after initially presenting as neutropaenia and splenomegaly. We describe a case of 47-year-old woman who was diagnosed simultaneously with FS and possible RA after testing positive for anticyclic citrullinated peptide antibody, but a negative rheumatoid factor. She had an excellent response to methotrexate. We review the existing literature of such cases and emphasise the importance of serological testing for RA in patients presenting with neutropaenia and splenomegaly, even in the absence of joint symptoms or prior diagnosis of RA.
30092207 Liquid biopsies to guide therapeutic decisions in rheumatoid arthritis. 2018 Nov Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease that has transitioned from a debilitating disease to a chronic, controllable disease. This has been possible due to the introduction of new treatment strategies like "treat-to-target," in which the clinician treats the patient aggressively enough to reach low disease activity or remission, and the introduction of new therapeutic agents, such as biological therapies, which can lead to the prevention of damage by early diagnosis and initiation of treatment. Attention is now being directed toward identifying the optimal treatment for each patient, one that will be the most efficient and have the least number of side effects. Much work has been done to find serologic and synovial biomarkers of response to various RA treatments. Proteomics, genomics and, in the past few years, metabolomics, have all been used in the quest of identifying these biomarkers. Blood-based liquid biopsies provide a minimally invasive alternative to synovial biopsies to identify cellular and molecular signatures that can be used to longitudinally monitor response and allow for personalized medicine approach. Liquid biopsies are comprised of cell-free DNA, immune circulating cells, and extracellular vesicles, and are being increasingly and successfully used in the field of oncology for diagnosis, progression, prognosis, and prediction of response to treatment. Recently, researchers have also begun investigating the usefulness of liquid biopsies in the field of rheumatology; in this review, we will focus on the potential of liquid biopsy blood samples as biomarkers of response to treatment in patients with RA.
29716677 One year in review 2018: pathogenesis of rheumatoid arthritis. 2018 Mar Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects joints. The several mechanisms involved in the development of the disease are not completely understood. It has been proposed that different environmental factors, such as cigarette smoking, occupational and atmospheric agents act as trigger stimuli for the development of RA in genetically predisposed individuals, leading to synovial hyperplasia and bone destruction. The initial disease stage of RA is associated with alteration of innate and adaptive immune system with consequent production of autoantibodies, targeting various molecules including modified self-epitopes. In the following stages of the disease, both the innate (e.g. dendritic cells, macrophages and neutrophils) and adaptive immune cells (e.g. B and T lymphocytes) contribute to the amplification and perpetuation of the chronic inflammatory state. The recognition of key cells, mediators and mechanisms implicated in the pathogenesis of RA could provide the basis for the development of new and precise disease-modifying anti-rheumatic drugs. Therefore, we reviewed the literature of the last year in order to find the new insights in RA pathogenesis.
27913876 Atherosclerosis assessment and rheumatoid arthritis. 2018 May BACKGROUND AND AIM: Rheumatoid arthritis is associated with increased morbidity and mortality due to atherosclerotic cardiovascular diseases. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme of phospholipase A2; it plays an important role in inflammation and atherosclerosis. Herein we aimed to investigate whether Lp-PLA2 activity is associated with atherosclerosis in patients with rheumatoid arthritis and compare the Lp-PLA2 activity with carotid intima media thickness (CIMT). PATIENTS AND METHODS: 25 patients with rheumatoid arthritis and 40 controls (20 patients with type 2 diabetes mellitus [DM] and 20 healthy controls) were included in the study. Frozen serum samples were used for analyzing Lp-PLA2 activity. Disease activity was calculated with DAS28 (Disease Activity Score 28) in the rheumatoid arthritis group. The mean CIMT was calculated in all participants. RESULTS: Lp-PLA2 activity was significantly higher in the DM group (p = 0.006) and LDL (Low density cholesterol levels) were lower in rheumatoid arthritis and healthy control groups compared with diabetics (p = 0.001 and p = 0.029, respectively). The mean CIMT was significantly higher in patients with type 2 DM (p = 0.047). CONCLUSION: Lp-PLA2 activity was not increased in the rheumatoid arthritis group when compared with healthy controls and the DM group. This result may be associated with low disease activity scores in patients with rheumatoid arthritis.
29426061 Microbiome-based mechanisms hypothesized to initiate obesity-associated rheumatoid arthrit 2018 Jun Worldwide, the growing obesity pandemic contributes to a range of chronic diseases. Recent epidemiological studies have suggested an association between obesity and the development of rheumatoid arthritis (RA), particularly among young women, whereby pro-inflammatory effects of adipokines provide one explanatory hypothesis. Yet, recent clinical and laboratory-based studies provide emerging evidence indicating microbiome involvement in RA initiation and development, including anti-citrullinated antibody formation and Th17 cell activation. Obesity and RA-associated microbiome alteration might provide a plausible link to address the impact of obesity to RA pathogenesis. The microbiome's influence on RA development - at mucosal as well as articular sites - and relevant pathophysiological mechanisms regarding obesity's association with RA are presented herein to discuss this hypothesis and aid understanding of obesity's role in RA development.
29859810 uPA/uPAR signaling in rheumatoid arthritis: Shedding light on its mechanism of action. 2018 Aug Rheumatoid arthritis (RA) is a systemic and chronic autoimmune inflammatory disorder affecting multiple joints. Various cytokines, chemokines and growth factors synergistically modulate the joint physiology leading to bone erosion and cartilage degradation. Other than these conventional mediators that are well established in the past, the newly identified plasminogen activator (PA) family of proteins have been witnessed to possess a multifactorial approach in mediating RA pathogenesis. One such family of proteins comprises of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR)/soluble-type plasminogen activator receptor (suPAR). PA family of proteins are classified into two types namely: uPA and tissue type plasminogen activator (tPA). Both these subtypes have been implicated to play a key role in RA disease progression. However during RA pathogenesis, uPA secreted by neutrophils, chondrocytes, and monocytes are designated to interact with uPAR expressed on macrophages, fibroblast-like synoviocytes (FLS), chondrocytes and endothelial cells. Interaction of uPA/uPAR promotes the disease progression of RA through secretion of several cytokines, chemokines, growth factors and matrix metalloproteinases (MMPs). Moreover, uPA/uPAR initiates inflammatory responses in macrophages and FLS through activation of PI3K/Akt signaling pathways. Furthermore, uPAR plays a dual role in osteoclastogenesis under the presence/absence of growth factors like monocyte-colony stimulating factor (M-CSF). Overall, this review emphasizes the role of uPA/uPAR on various immune cells, signaling pathways and osteoclastogenesis involved in RA pathogenesis.
29205904 Dosing down and then discontinuing biologic therapy in rheumatoid arthritis: a review of t 2018 Feb AIM: To review the published studies that dose down and then discontinue biologic therapy in patients with rheumatoid arthritis (RA), particularly concerning the criteria for such dosing and the impact on clinical outcomes. METHODS: Published studies conducted in patients with RA that sequentially decreased the dose and then discontinued therapy were included if one or more of the following biologic disease modifying antirheumatic drugs (bDMARDs) was evaluated: abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab or tocilizumab. RESULTS: Five studies qualified for inclusion. The populations of patients with RA were heterogeneous among the studies; patients were required to have low disease activity (LDA) or to be in remission prior to dose titration. Approximately 25-65% of patients successfully decreased and in some cases, discontinued the bDMARD. However, the flare rate was higher than for the patients who remained on a standard dose. The only variable that predicted relapse in more than one study was down-titration of the bDMARD dose. CONCLUSION: In patients who have achieved LDA or remission, down-titration and discontinuation of bDMARD therapy may be attempted, with careful monitoring. However, it is likely that some patients will flare, and it is not known how to predict these patients.
30179207 Bone erosions in rheumatoid arthritis: recent developments in pathogenesis and therapeutic 2018 Sep 1 Bone erosions develop early in the course of rheumatoid arthritis (RA) and deteriorate progressively, causing joint damage and resulting in impaired functional capacity of patients. During the last years, considerable number of studies has increased our understanding of the pathogenetic mechanisms mediating the development of bone erosions in RA. Increased production of RANKL and other cytokines, dysregulation of innate immune mechanisms, autoantibodies specific to RA and alterations of microRNA expression stimulate differentiation and function of osteoclasts, which are responsible for the development of bone erosions. Besides, increased levels of cytokines, overproduction of antagonists of the canonical Wnt signaling pathway and deficient production of bone morphogenetic proteins result in impaired osteoblast differentiation and function, undermining the capacity of bone erosions to repair. Disease-modifying antirheumatic drugs, synthetic or biological, currently used in the treatment of RA, can halt the progression of bone erosions and may even lead to partial repair, although complete repair is unattainable. Targeting pathogenetic mechanisms participating in the erosive process may add to the therapeutic effect of DMARDs and help in the prevention or repair of bone erosions. However, more studies are still needed to confirm whether such therapeutic strategies are effective.
30251905 The potential of PTPN22 as a therapeutic target for rheumatoid arthritis. 2018 Oct PTPN22 encodes a lymphoid-specific tyrosine phosphatase (LYP) that is a master regulator of the immune response. This gene is a major susceptibility factor for a wide range of autoimmune conditions, including rheumatoid arthritis (RA) for which it represents the strongest non-HLA contributor to disease risk. A missense PTPN22 allele (R620W) affecting the protein-protein interaction of LYP with other relevant players was described as the functional variant of the association. This review will focus on the role of PTPN22 in the pathogenic mechanisms underlying RA predisposition and discuss the possibility of developing LYP-based treatment strategies with a potential application in clinical practice. Areas covered: This review covers the literature showing how PTPN22 is implicated in signalling pathways involved in the autoimmune and autoinflammatory processes underlying RA. Insights obtained from studies aimed at developing novel selective LYP suppressors for treating RA are summarized. Expert opinion: Targeting key risk factors during the early steps of the disease may represent a good strategy to accomplish complete disease remission. As cumulating evidences suggest that PTPN22 R620W is a gain-of-function variant, a growing interest in developing LYP inhibitors has arisen. The potential efficacy and possible application of such compounds are discussed.
29336618 Rheumatoid arthritis: A single-center Egyptian experience. 2018 Apr OBJECTIVE: Demonstration of rheumatoid arthritis (RA) characteristics in a large cohort of Egyptian patients. METHODS: Retrospective analysis of data of 3219 RA patients attending the Rheumatology outpatient clinic, Kasr Alainy Hospital, Cairo University; from January 1995 till December 2015. RESULTS: Mean age at disease onset was 36.1 ±13.4 years; 2774 (84%) were females and mean disease duration was 12.9 ±7.9 years. Regarding number of joint affected at disease onset; polyarticular pattern was found in 77.1%, pattern of joint involvement; combined small and large joints involvement was in 83.2%, subcutaneous nodules in 14.2%, interstitial lung disease in 0.3%, secondary Sjogren's syndrome in 10.5%, hand bony erosions at diagnosis in 20.6%. Rheumatoid factor was positive in 52%. There was annual increase in the newly diagnosed cases (P = 0.017) reflecting increase in patients' awareness and improvement of medical service, also annual increase in: mean age of onset (P < 0.001) reflecting changes in health measures, also in cases with monoarticular or oligoarticular patterns at disease onset (P = 0.02, 0.01 respectively) reflecting earlier diagnosis of patients and in patients with small joint involvement (P = 0.001) with a significant decline in: polyarticular pattern (P = 0.001), combined small and large joint affection (P < 0.001), and number of cases with hand bony erosions (P = 0.01) denoting earlier diagnosis, tight disease control. CONCLUSION: We found a female predominance, younger age at disease onset, lower frequency of extra articular manifestations, more frequent polyarticular pattern at disease onset and less erosive disease, denoting changing referral patterns, earlier diagnosis, improved disease control in Egyptian RA patients over 2 decades. ABBREVIATIONS: SNs: Subcutaneous nodules; 2ry SS: 2ry Sjogren's syndrome; ILD: Interstitial lung disease; ACPA: Anti-cyclic citrullinated peptide antibodies; DMARDs: Disease modifying anti-rheumatic drugs.
30176641 [Early reumatoid arthritis]. 2018 Rheumatoid arthritis (RA) is a systemic, autoimmune disease characterized by synovitis and irreversible joint destruction. RA development is a multi-stage process conditioned by the presence of genetic and environmental risk factors on the basis of which systemic immunization develops. The best known genetic factor predisposing to RA development is the polymorphism of HLA-DRB1 region of the major histocompatibility complex. Among environmental factors, importance in the pathogenesis of RA is attributed to the development of inflammation of the respiratory tract and chronic periodontitis caused by Porphyromonas gingivalis. The presence of antibodies and biomarkers of inflammation is well established before the onset of clinical symptoms of arthritis. The most well-known serological markers of RA include rheumatoid factor (RF) and anti-citrullinated peptide/proteins antibodies (ACPA). The search for new biomarkers that will allow the diagnosis of arthritis in the early, pre-destructive phase of the disease is still underway. The compound of anti-carbamylated protein antibodies (anti-CarP), adipocytokines or vitamin D with development of RA is tested. Several clinical studies have shown that disease-modifying anti-rheumatic drug (DMARD) therapy introduced at an early stage, referred to as a "window of opportunity", is associated with long-term benefits in the form of long-term remission and even complete remission of the disease.
29731460 [Diagnosis and treatment of rheumatoid arthritis:toward the best practice. Management of e 2018 Elderly rheumatoid arthritis(RA)is classified into 2 clinical subsets, elderly-onset RA(EORA)and younger-onset elderly RA. Anti-CCP antibody positive, high disease activity, presence of bone erosion are associated with progression of joint destruction of EORA, and intensive treatment using a treat-to-target strategy is needed in the patients with the poor prognostic factors. Working ability is one of most important goals for RA and also non-frail status should be goal of elderly RA, since it is associated with health expectancy. Biological DMARDs are slightly less or equally effective in reducing disease activity in elderly patients, and disease duration may have a greater impact on disease outcomes than age. Elderly patients had multi-morbidities and risk factors for serious infections, which make it difficult to establish a treatment strategy for elderly RA. We will discuss the treatment strategy of elderly RA in this review.
30296974 Update on magnetic resonance imaging and ultrasound in rheumatoid arthritis. 2018 Sep Rheumatoid arthritis (RA) disease activity often remains difficult to assess and quantify accurately. As a result, numerous measures using various techniques to estimate clinical activity have been developed for clinical research and care. More objective imaging biomarkers for early detection and accurate, quantitative measurement of the disease burden are therefore of interest both for clinical use and for investigational studies. Two widely studied imaging biomarkers are magnetic resonance imaging (MRI) and ultrasound (US), imaging tests that are increasingly available to clinicians. While substantial and increasing evidence has been reported that these tools are valid and provide advantages in both clinical trials and clinical assessments, more information is needed to inform their appropriate use in routine clinical care. The goals of this review are to outline the current literature regarding each of these objective imaging tools, assess their strengths and limitations, and to clarify knowledge gaps to be filled before these techniques may be more optimally utilised.
30058527 One year in review 2018: ultrasonography in rheumatoid arthritis and psoriatic arthritis. 2018 Jul Ultrasound is playing an increasingly important role in the differential diagnosis and monitoring of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This technique is more sensitive and specific than clinical examination to detect active synovitis, and the identification of specific synovitis patterns enable differentiation of PsA from RA and other entities. Ultrasound verified inflammation changes along with clinical improvement during therapy, and ultrasound was shown to predict future clinical and structural outcomes thus complementing the clinical risk assessment of patients. In the present review, we summarised the scientific evidence published in 2017 focussing on the use of ultrasonography for clinically relevant and pragmatic aspects of diagnosis and management of RA and PsA.
29369089 Using technology to support clinical care and research in rheumatoid arthritis. 2018 May PURPOSE OF REVIEW: As digital technology becomes more ubiquitous, understanding the current state-of-the-art in digital information use for clinical care and research for patients with rheumatoid arthritis (RA) is timely and relevant. RECENT FINDINGS: The opportunities for recording and utilizing high-quality data from rheumatologists are reviewed, as well as opportunities from collecting, integrating and analysing patient-generated data to deliver a step-change in the support and management of RA. SUMMARY: Once greater adoption, standardization and implementation of relevant RA measures are in place within electronic health records (EHRs), patient care will improve and the ability to learn from aggregate experiences increases dramatically. Incorporating passive and patient-reported outcomes into self-management apps and integrating such data into the patient's health record will provide more responsive and better treatment results.