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ID PMID Title PublicationDate abstract
33117162 Potential Advantages of Bioactive Compounds Extracted From Traditional Chinese Medicine to 2020 Bone destruction is an important pathological feature of rheumatoid arthritis (RA), which finally leads to the serious decline of life quality in RA patients. Bone metabolism imbalance is the principal factor of bone destruction in RA, which is manifested by excessive osteoclast-mediated bone resorption and inadequate osteoblast-mediated bone formation. Although current drugs alleviate the process of bone destruction to a certain extent, there are still many deficiencies. Recent studies have shown that traditional Chinese medicine (TCM) could effectively suppress bone destruction of RA. Some bioactive compounds from TCM have shown good effect on inhibiting osteoclast differentiation and promoting osteoblast proliferation. This article reviews the research progress of bioactive compounds exacted from TCM in inhibiting bone destruction of RA, so as to provide references for further clinical and scientific research.
32734482 Understanding the Role of Interleukin-6 (IL-6) in the Joint and Beyond: A Comprehensive Re 2020 Sep Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune disorder involving inflammation and progressive destruction of the joints, affecting up to 1% of the population. The majority of patients with RA have one or more comorbid conditions, the most common being cardiovascular disease, osteoporosis, and depression, the presence of which are associated with poorer clinical outcomes and lower health-related quality of life. RA pathogenesis is driven by a complex network of proinflammatory cells and cytokines, and of these, interleukin-6 (IL-6) plays a key role in the chronic inflammation associated with RA. Through cell signaling that can be initiated by both membrane-bound and soluble forms of its receptor, IL-6 acts both locally to promote joint inflammation and destruction, and in the circulation to mediate extra-articular manifestations of RA, including pain, fatigue, morning stiffness, anemia, and weight loss. This narrative review describes the role of IL-6 in the pathogenesis of RA, its comorbidities, and extra-articular systemic manifestations, and examines the effects of the IL-6 receptor inhibitors sarilumab and tocilizumab on clinical endpoints of RA, patient-reported outcomes, and common comorbidities and extra-articular manifestations.
32362827 Kunxian Capsule for Rheumatoid Arthritis: Inhibition of Inflammatory Network and Reducing 2020 Tripterygium wilfordii Hook.f and Tripterygium hypoglaucum (H.Lév.) Hutch is effective herbs to prevent aggravation of Rheumatoid arthritis (RA). However, both of them show severe side effects in the reproductive system and other systems. Kunxian Capsule (KX), a Traditional Chinese Medicine (TCM) patent prescription, comprised of 4 herbs, including H.Lév. Hutch, is reported to be an available prescription in treating RA with fewer side effects as compares to Tripterygium tablets. To reveal the pharmacological mechanism of KX in RA treatment and side effect alleviation, we collected related information of KX from open-access databases and performed various analyses. 1354 targets were identified in KX. These targets were enriched in the calcium signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway and PI3K-AKT signaling pathway, forming biological functions, such as cofactor binding, coenzyme binding, etc. These pathways or functions mostly affect cell cycle, differentiation, and maturation of Th17 cells, macrophage, and synovial fibroblast. These targets also act on the IL-17 signaling pathway, Th17 cell differentiation signaling pathway and TNF signaling pathway, which is related to inflammation response inhibition. Next, a disease network was constructed, which indicated IMPDH2, MTHFD1 are the key genes answering for the side effects of H.Lév. Hutch. The side effect-related genes lead to the negative regulation of nucleic acid, which could be restored by the rest 3 herbs through some positive amino acid metabolism. In conclusion, KX is a relatively safe alternative approach in RA intervention.
32082684 Platelet Rich Plasma for Treatment of Rheumatoid Arthritis: Case Series and Review of Lite 2020 Platelet-rich plasma (PRP) is an autologous blood product with platelets above circulating levels and releases several growth factors after activation. PRP may help to decrease joint inflammation by modulating synovial cell proliferation and differentiation and inhibition of catabolic pathways in various articular conditions. Though PRP has shown good efficacy in osteoarthritis and other musculoskeletal conditions such as synovitis, epicondylitis, skeletal muscle injuries, and tendinopathy, there is limited experience for the use of PRP in patients with rheumatoid arthritis. Precise mechanisms of action of PRP are not known. We present clinical experience for treatment with PRP (2-4 ml) in four patients with rheumatoid arthritis who had inadequate response and persistent pain and inflammation with intra-articular steroids. Irrespective of past and ongoing treatments and duration of disease, all patients showed improvement in the visual analog scale and disease activity score of 28 joints at 4 and 8 weeks after injection. There was an improvement in joint inflammation on ultrasound imaging in some patients. These effects were sustained for up to 1 year. No adverse effects were reported in any patient. PRP may be a safe and useful therapy in patients with rheumatoid arthritis who fail to respond to one or more established treatment options.
33343364 Regulating Gut Microbiome: Therapeutic Strategy for Rheumatoid Arthritis During Pregnancy 2020 Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and bone destruction. Microbial infection is considered to be the most important inducement of RA. The pregnancy planning of women in childbearing age is seriously affected by the disease activity of RA. Gut microbiome, related to immunity and inflammatory response of the host. At present, emerging evidence suggested there are significant differences in the diversity and abundance of gut microbiome during pregnancy and lactation, which may be associated with the fluctuation of RA disease activity. Based on these research foundations, we pioneer the idea of regulating gut microbiome for the treatment of RA during pregnancy and lactation. In this review, we mainly introduce the potential treatment strategies for controlling the disease activity of RA based on gut microbiome during pregnancy and lactation. Besides, we also briefly generalize the effects of conventional anti-rheumatic drugs on gut microbiome, the effects of metabolic changes during pregnancy on gut microbiome, alteration of gut microbiome during pregnancy and lactation, and the effects of anti-rheumatic drugs commonly used during pregnancy and lactation on gut microbiome. These will provide a clear knowledge framework for researchers in immune-related diseases during pregnancy. Regulating gut microbiome may be a potential and effective treatment to control the disease activity of RA during pregnancy and lactation.
32552050 MiRNA-6089 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and in 2020 Jun 17 Several studies have suggested that fibroblast-like synoviocytes (FLSs) and miRNAs are implicated in the pathogenesis of rheumatoid arthritis (RA). This study was aimed to evaluate the function of miR-6089 in the regulation of RA-FLSs. The levels of miR-6089 were detected to be significantly lower in the synovial tissues and FLSs of RA than in the healthy synovial tissues and FLSs. The miR-6089 up-regulation in RA-FLSs significantly inhibited the proliferation and promoted cell apoptosis accompany with an increase protein expression of cleaved-Caspase-3, -8 and -9. Furthermore, CCR4 was determined to target miR-6089 directly, and its expression was significantly increased in the synovial tissues of RA than in the healthy synovial tissues. The overexpression of CCR4 reversed the effect of miR-6089 on proliferation and apoptosis in RA-FLSs effectively. In conclusion, our study suggests that the miR-6089 may be a potential target for prevention and treatment of RA.
32489719 The Link Between Rheumatoid Arthritis and Dementia: A Review. 2020 Apr 27 BACKGROUND:  This study explored the relationship between rheumatoid arthritis (RA) and dementia. These two diseases are a significant health burden that affects the older population, although they have also manifested in young people to a smaller extent. METHODOLOGY:  The study entailed a detailed literature review of articles on RA and dementia. The peer-reviewed articles were sourced from reputable databases such as Research Gate, National Center for Biotechnology Information, PubMed, and Google Scholar. RESULTS:  RA is a chronic disorder that affects millions of Americans. Dementia, on the other hand, is associated with diminishing cognitive capabilities that impair daily living. Both diseases are associated with older persons and genetic factors. Besides, the inflammation associated with RA reduced blood flow to vital body organs, which increases the risk of developing dementia. Additionally, the study revealed that medications used by RA patients increase the risk of developing dementia. However, biological therapies such as tumor necrosis factor (TNF) inhibitors can lower the risk of dementia. CONCLUSION:  There is a need to develop diagnostic procedures that will enable early diagnosis and commencement of treatment to slow down the progression of both disorders. Furthermore, managing these disorders effectively mandates increased awareness about the causality and risk factors of both diseases, especially among young people and at-risk populations to promote lifestyle change and increased uptake of primary care services.
33025887 One year in review 2020: pathogenesis of primary Sjögren's syndrome. 2020 Jul The pathogenesis of primary Sjögren's syndrome (pSS) remains poorly understood. However, important efforts have been made during the last few months. In this review, following the others of this series we will summarise the most recent literature on pSS pathogenesis focusing in particular on new insights into pSS animal models, genetics and epigenetics, innate and adaptive immune system abnormalities and tertiary lymphoid structures. Hopefully, novel insights into pSS pathogenesis will pave the way to new therapeutic approaches to the disease improving patients' management and prognosis.
34085019 Recurrent and refractory corneal perforation secondary to rheumatoid arthritis treated wit 2020 Jul Rheumatoid arthritis (RA) can affects many organs including the eyes. Corneal perforation in the form of peripheral ulcerative keratopathy can be debilitating and difficult to manage. A 48-year-old female with known RA presented with sudden loss of vision in her left eye, she was diagnosed with left corneal perforation secondary to severe dry eye. Penetrating keratoplasty (PKP) and punctum occlusion were done. Amniotic membrane transplant (AMT) was done 1 month later due to nonhealing epithelial defect. Her RA was clinically inactive, and no changes in her current medications were made. However, 4 months later, she presented with a second corneal perforation with melting. She had another PKP and AMT with permanent temporal tarsorrhaphy. Cyclosporine 100 mg P. O. twice daily was added, but after 5 months, she presented again with a third left corneal perforation with melting. Again, PKP and AMT with tarsorrhaphy were done, and she was started on infliximab. Since then, she had a stable graft with no further corneal perforations. In summary, patients with RA can have corneal perforations even if other signs of RA are absent. If the systemic treatment that is used to treat RA fails, one should consider using other classes of drugs, such as monoclonal antibodies (e.g., rituximab), tumor necrosis factor alpha blockers (such as infliximab or adalimumab), interleukin (IL)-1 receptor antagonists (e.g., anakinra), or IL-6 receptor antagonist (e.g., tocilizumab).
33598269 Fecal microbiota transplantation for rheumatoid arthritis: A case report. 2021 Feb No previous case of using fecal microbiota transplantation (FMT) to treat rheumatoid arthritis (RA) has been reported. We report a case of a patient with refractory RA successfully treated with FMT indicating that FMT may have a good therapeutic effect on RA.
33681234 Self-Balance of Intestinal Flora in Spouses of Patients With Rheumatoid Arthritis. 2020 We sought to characterize and assess differences in compositions of intestinal flora between patients with rheumatoid arthritis (RA) and their respective spouses. Eighty volunteers were recruited, including 30 pairs of RA patients and their spouses, and 20 healthy individuals. Fresh stool samples were collected, processed, and 16S rRNA-sequencing was performed. Data were analyzed using an operational taxonomic units-based method, and community structure assessments were performed. Community composition analysis indicated that there were similar intestinal microbiota structures in RA and in their respective spouses. Gut microbiota in spouses of RA were different from those of the healthy controls group, but these differences were not significant. We found that Blautia spp. and Streptococcus spp. were two most associated species in RA and these taxa were significantly higher in comparison to healthy controls. In contrast, our findings suggested that Roseburia spp. and Lachnoclostridium spp. were significantly lower in the RA in comparison to healthy controls. In conclusion, RA patients shared similar gut microbiota pattern with their spouses which were different from healthy individuals. The findings suggest that disturbance of the balance of gut microbiota may play an important role in the dynamics of pathogenesis of RA.
32411931 Theory-informed interventions to promote physical activity and reduce sedentary behaviour 2020 Mar Moderate-intensity physical activity (PA) is recommended for the management of Rheumatoid Arthritis (RA). Recent evidence suggests that reducing sedentary behaviour (promoting 'sedentary breaks' and light intensity PA) may also offer potential for improving RA outcomes, independently of the benefits of moderate-intensity PA. Unfortunately, people living with RA engage in very little moderate-intensity PA, and the spend the majority of the day sedentary. Interventions to support PA and sedentary behaviour change in this population are therefore required. Psychological theory can provide a basis for the development and implementation of intervention strategies, and specify the cognitive processes or mechanisms assumed to result in behavioural change. Application of psychological theory to intervention development and evaluation, therefore, permits evaluation of "how things work", helping to identify optimal intervention strategies, and eliminate ineffective components. In this review, we provide an overview of existing PA and sedentary behaviour change interventions in RA, illustrating the extent to which current interventions have been informed by psychological theories of behaviour change. Recommendations are provided for future interventional research in this domain, serving as a reference point to encourage proper application of behavioural theories into intervention design, implementation and appraisal.
33275251 Sjögren syndrome associated with obsessive-compulsive disorder. 2020 Nov OBJECTIVE: To describe a patient with Sjögren syndrome (SS) associated with obsessive-compulsive disorder (OCD). PATIENTS AND METHODS: Case report and systematic review of the literature. CASE REPORT: A 40-year-old female patient with a history of xerostomia and xerophthalmia initiated in 2015. She also had a history of changing her behavior, and she practices rituals, recurrent obsessions, and compulsions. She was diagnosed with OCD. She was treated with fluoxetine associated with risperidone and then was changed for aripiprazole 10 mg/day. Cognitive-behavioral therapy was also applied. She had good control of the obsessions with these drugs and psychotherapy. Laboratory tests showed positive antinuclear antibodies, anti-Ro/SS-A, and-La/SS-B antibodies. Schirmer test, break up time, and positive green lisamin were all positive. Scintigraphy and ultrasound of salivary glands were positive. A diagnosis of Sjögren syndrome was determined. She was treated with HCQ, vitamin D3 50,000 IU/week, omega-3 2 g, and artificial tears with a good response. Currently, 5 years later, the patient is asymptomatic and has OCD under adequate control even without drugs. CONCLUSIONS: This case illustrates a rare case of a patient with SS who evolved with OCD.
33330493 Roles of MicroRNAs in Bone Destruction of Rheumatoid Arthritis. 2020 As an important pathological result of rheumatoid arthritis (RA), bone destruction will lead to joint injury and dysfunction. The imbalance of bone metabolism caused by increased osteoclast activities and decreased osteoblast activities is the main cause of bone destruction in RA. MicroRNAs (MiRNAs) play an important role in regulating bone metabolic network. Recent studies have shown that miRNAs play indispensable roles in the occurrence and development of bone-related diseases including RA. In this paper, the role of miRNAs in regulating bone destruction of RA in recent years, especially the differentiation and activities of osteoclast and osteoblast, is reviewed. Our results will not only help provide ideas for further studies on miRNAs' roles in regulating bone destruction, but give candidate targets for miRNAs-based drugs research in bone destruction therapy of RA as well.
33036446 Predictors of Flares in Patients with Rheumatoid Arthritis Who Exhibit Low Disease Activit 2020 Oct 7 Using nationwide cohort data, this study evaluated predictors of flares in patients with rheumatoid arthritis (RA) who exhibit low disease activity (LDA) and the effects of flares on clinical outcomes. The Korean Observational Study Network for Arthritis (KORONA) registry is a nationwide Korean RA-specific cohort registry that collects data annually from 5.077 patients, with RA in 23 centers across South Korea. This study used data from 1.717 patients with RA who exhibited LDA [28-joint disease activity score (DAS28) < 3.2] at enrollment. Flares were defined as an increase in DAS28, compared with the previous value of > 1.2 or > 0.6, if the concurrent DAS28 was ≥ 3.2. Cox regression analysis was used to identify baseline predictors of flares. Of the 1.717 patients with RA, 566 (33.0%) experienced flares during the 2-year study period. An analysis of baseline characteristics of flare and non-flare groups revealed that more women and non-smokers were present in the flare group than in the non-flare group; the flare group also had higher scores on physician's and patient's pain and fatigue visual analogue scales (VAS) and the health assessment questionnaire (HAQ). In a multivariate analysis, physician's VAS score, hemoglobin level, and HAQ score were significant predictors of flares. A high physician's VAS score, low hemoglobin, and high HAQ score at baseline were significant predictors of flares in patients with RA who exhibited LDA.
32849810 Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine o 2020 Rheumatoid arthritis (RA) is a complex disease triggered by the interaction between genetics and the environment, especially through the shared epitope (SE) and cell surface calreticulin (CSC) theory. However, the available evidence shows that genetic diversity and environmental exposure cannot explain all the clinical characteristics and heterogeneity of RA. In contrast, recent studies demonstrate that epigenetics play important roles in the pathogenesis of RA, especially DNA methylation and histone modification. DNA methylation and histone methylation are involved in innate and adaptive immune cell differentiation and migration, proliferation, apoptosis, and mesenchymal characteristics of fibroblast-like synoviocytes (FLS). Epigenetic-mediated regulation of immune-related genes and inflammation pathways explains the dynamic expression network of RA. In this review, we summarize the comprehensive evidence to show that methylation of DNA and histones is significantly involved in the pathogenesis of RA and could be applied as a promising biomarker in the disease progression and drug-response prediction. We also explain the advantages and challenges of the current epigenetics research in RA. In summary, epigenetic modules provide a possible interface through which genetic and environmental risk factors connect to contribute to the susceptibility and pathogenesis of RA. Additionally, epigenetic regulators provide promising drug targets to develop novel therapeutic drugs for RA. Finally, DNA methylation and histone modifications could be important features for providing a better RA subtype identification to accelerate personalized treatment and precision medicine.
32963891 Arthritis and the role of endogenous glucocorticoids. 2020 Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.
31998313 Syndecan-3 in Inflammation and Angiogenesis. 2019 Syndecans are a four member multifunctional family of cell surface molecules with diverse biological roles. Syndecan-3 (SDC3) is the largest of these, but in comparison to the other family members relatively little is known about this molecule. SDC3 null mice grow and develop normally, all be it with subtle anatomical phenotypes in the brain. Roles for this molecule in both neuronal and brain tissue have been identified, and is associated with altered satiety responses. Recent studies suggest that SDC3 expression is not restricted to neuronal tissues and has important roles in inflammatory disorders such as rheumatoid arthritis, disease associated processes such as angiogenesis and in the facilitation of infection of dendritic cells by HIV. The purpose of this review article is to explore these new biological insights into SDC3 functions in inflammatory disease.
33262665 Clinicodemographic Profiles of Rheumatoid Arthritis Patients from a Single Center in Saudi 2020 PURPOSE: Rheumatoid arthritis (RA), if left untreated, can lead to joint damage and deformity, disability, and even death. Hence, early diagnosis and management are essential to improve clinical and functional outcomes. This study aimed to identify the most common variables and risk factors related to RA activity among patients living in the Kingdom of Saudi Arabia (KSA). PATIENTS AND METHODS: This study was conducted between January 2018 and March 2019 on consecutive patients diagnosed with RA at a tertiary care hospital in KSA. Adult patients (≥18 years old) diagnosed with RA based on the American College of Rheumatology 2010 criteria were recruited. The Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) and health assessment questionnaire disability index (HAQ-DI) were calculated for 75 patients attending the rheumatology clinic during the study period to evaluate the rate of remission and functional capacity, and to compare findings with other local studies after assessing the relationship of these factors with medication use and existing comorbidities. RESULTS: The majority of the 75 patients were female (n=64), with a mean age of 49.7 years and average disease duration of 130 days. The median HAQ-DI was less than 0.5 (range 0-1.95). The DAS28-CRP scores revealed moderate disease activity in 45.3% and low disease or remission in 38.6% of the patients. Many patients (45.3%) were treated with methotrexate, and the most commonly used biological treatment was adalimumab in 14.6%. Comorbidities included hypertension (26.7%) and diabetes mellitus (18.7%). There was a strong association between cardiovascular diseases and a high DAS28-CRP score (p < 0.001). CONCLUSION: A higher RA activity rate was observed. This may be related to difficultly accessing rheumatology clinics in our facility and financial difficulties accessing biological treatments.
32704284 Effect of Ramadan fasting on disease activity in patients with rheumatoid arthritis presen 2020 Jul BACKGROUND AND OBJECTIVE: Rheumatoid Arthritis (RA) is a common inflammatory disorder affected by various factors, including fasting. The objective of the study was to establish the effect of Ramadan fasting on DAS 28 in Rheumatoid Arthritis patients. METHODS: In this observational cohort study done in department of rheumatology, Mayo hospital, Lahore, between May 2019 to July 2019, 240 patients were divided in fasting (n=120) and non-fasting cohort (n=120) based on their own choice. Mean DAS-28 scores before and after Ramadan was compared in both cohorts with appropriate statistical analyses. RESULTS: Two hundred forty participants, (74 males, 166 females), were recruited. Baseline DAS of fasting group was significantly low (4.35±0.9) as compared to non-fasting group (5.07±0.91). Paired t-test showed statistically significant improvement in fasting and non-fasting groups in total and in both genders (p=0.000). Mean improvement in DAS was numerically greater and statistically significant (p=0.000) in non-fasting group (1.08±0.62) as compared to fasting ones (0.86±0.61). Post-Ramadan DAS was, however, significantly low in fasting group (3.49±0.9) versus non-fasting group (3.98±1.0) (p=0.000). CONCLUSION: DAS 28 score decreased in both non-fasting as well as fasting patients of RA during the month of Ramadan. RA patients with moderate disease activity, who want to keep fast, can be allowed to do so without any fear of disease worsening.