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

ID PMID Title PublicationDate abstract
33610711 Systems pharmacology-based dissection of mechanisms of Tibetan medicinal compound Ruteng a 2021 May 23 ETHNOPHARMACOLOGICAL RELEVANCE: Compound Ruteng (CRT) is a prescribed formulation based on the theory of Tibetan medicine for the treatment of yellow-water-disease. It is consisted with 7 medicinal material include Boswellia carterii Birdw (named "Ruxiang" in Chinese); Tinospora sinensis (Lour.) Merr. (named "Kuan-Jin-Teng" in Chinese), Cassia obtusifolia L (named "Jue-Ming-Zi" in Chinese); Abelmoschus manihot (L.) Medic (named "Huang-Kui-Zi" in Chinese); Terminalia chebula Retz. (named "He-Zi" in Chinese); Lamiophlomis rotata (Benth.) Kudo (named "Du-Yi-Wei" in Chinese) and Pyrethrum tatsienense (Bur. et Franch.) Ling (named "Da-Jian-Ju" in Chinese). They are widely distributed in Tibet area of China and have been used to treat rheumatism, jaundice, and skin diseases for centuries. AIM OF THE STUDY: The present study was conducted to investigate the anti-arthritis effect of CRT and to disclose the systems pharmacology-based dissection of mechanisms. MATERIALS AND METHODS: The chemical constituents in CRT were identified using HPLC method, and CRT candidate targets against RA were screened by network pharmacology-based analysis and further experimentally validated based on collagen-induced arthritis (CIA) rat model. Furthermore, therapeutic mechanisms and pathways of CRT were investigated. RESULTS: 391 potential targets (protein) were predicted against 92 active ingredients of 7 medicinal materials in CRT. Enrichment analysis and molecular docking studies also enforced the practiced results. X-ray based physiological imaging showed the attenuated effect of CRT on paw swelling, synovial joints and cartilage with improved inflammation in CIA rats. Moreover, the expression of biomarkers associated with RA such as MMP1, MMP3 and MMP13 and TNF-a, COX2 and iNOS are down-regulated in ankle joints, serum, or liver. CONCLUSION: In conclusion, CRT compound could attenuate RA symptoms and active ingredients of this compound could be considered for drug designing to treat RA.
34643160 Rheumatoid cachexia in early rheumatoid arthritis: prevalence and associated variables. 2021 Oct 13 OBJECTIVE: Rheumatoid cachexia (RC) is prevalent among patients with established rheumatoid arthritis (RA). Although changes in muscle mass and fat mass have been reported in early RA, these findings have not been classified according to existing RC definitions. This study aimed to describe the prevalence of RC and associated variables in patients with early RA. METHOD: This cross-sectional study included 87 patients. Body composition was evaluated with dual-energy X-ray absorptiometry after a median disease duration of 15 months. RC was defined as a fat-free mass index < 10th percentile and fat mass index > 25th percentile. We also assessed the erythrocyte sedimentation rate (ESR), C-reactive protein, Disease Activity Score in 28 joints, aerobic capacity, physical activity, traditional cardiovascular disease risk factors, functional disability, and sociodemographic data. Associations between RC and the independent variables were determined with logistic regression analyses. RESULTS: The prevalence of RC was 24%. RC was significantly associated [odds ratio (95% confidence interval)] with aerobic capacity [0.28 (0.09-0.89), p = 0.030], low-intensity physical activity [0.77 (0.60-0.99), p = 0.048], body mass index [0.78 (0.70-0.92), p = 0.002], waist circumference [0.96 (0.92-0.99), p = 0.023], body weight [0.94 (0.90-0.98), p = 0.004], and ESR at the time of diagnosis [1.02 (1.00-1.05), p = 0.033]. All of these associations remained significant after adjusting for age and gender. CONCLUSION: RC was highly prevalent in early RA. Patient outcome may be improved by detecting this condition early and applying treatments for improving inflammation, aerobic capacity, physical activity, and body composition.
33618728 Arthritis as an initial presentation of malignancy: two case reports. 2021 Feb 23 BACKGROUND: Arthritis is rarely reported as a paraneoplastic manifestation of occult malignancy. We report herein two cases of paraneoplastic arthritis due to occult malignancy. CASE 1: The patient was a 65-year-old woman of asian descent who was a former smoker with a history of spine surgery performed for L4/L5 degenerative disc disease. She presented with a 1-month history of oligoarthritis affecting both ankle joints and early morning stiffness of about 3 hours. Laboratory tests were positive for antinuclear antibody at a titer of 1:320 (speckled) but negative for rheumatoid factor. She was treated for seronegative spondyloarthritis and started on prednisolone without much improvement. A routine chest radiograph incidentally revealed a right lung mass which was found to be adenocarcinoma of the lung. She was treated with gefitinib and her arthritis resolved. CASE 2: The patient was a 64-year-old woman of asian descent, nonsmoker, who presented with a chief complaint of asymmetrical polyarthritis involving her right wrist, second and third metacarpophalangeal joints, and first to fifth proximal interphalangeal joints. She was treated for seronegative rheumatoid arthritis (RA) and started on sulfasalazine, with poor clinical response. Six months later, she developed abdominal pain which was diagnosed as ovarian carcinoma by laparotomy. Her arthritis resolved following treatment of her malignancy with chemotherapy. CONCLUSION: In summary, paraneoplastic arthritis usually presents in an atypical manner and responds poorly to disease-modifying antirheumatic drugs. Accordingly, we recommend screening for occult malignancy in patients presenting with atypical arthritis.
31643567 Tocilizumab. 2012 Tocilizumab is a humanized monoclonal antibody to the interleukin-6 (IL-6) receptor which is used in the therapy of rheumatoid arthritis and other autoinflammatory conditions. Tocilizumab commonly causes mild serum aminotransferase elevations that are usually short lived and asymptomatic, but has also been linked to rare instances of clinically apparent liver injury with jaundice and occasional reactivation of hepatitis B.
31643297 Sarilumab. 2012 Sarilumab is a human monoclonal IgG1 antibody to the interleukin-6 (IL-6) receptor which is used in the therapy of rheumatoid arthritis and other autoinflammatory conditions. Sarilumab commonly causes mild serum aminotransferase elevations which are usually short lived and asymptomatic and has also been linked to rare instances of clinically apparent liver injury with jaundice.
33553962 Correction to Naringin in Combination with Isothiocyanates as Liposomal Formulations Poten 2021 Feb 2 [This corrects the article DOI: 10.1021/acsomega.0c04300.].
33836697 Person-centred care in osteoarthritis and inflammatory arthritis: a scoping review of peop 2021 Apr 9 BACKGROUND: Arthritis, regardless of cause, has significant physical, social and psychological impacts on patients. We aimed to identify the non-healthcare needs perceived by patients with inflammatory arthritis (IA) and osteoarthritis (OA), and to determine if these differ. METHODS: We electronically searched MEDLINE, PsycINFO, EMBASE and CINAHL (1990-2020) systematically to identify non-healthcare-related needs of people with IA or OA. All citations were screened and quality appraised by two reviewers. Data was extracted by a single reviewer. RESULTS: The search identified 7853 citations, with 31 studies included (12 for OA, 20 for IA). Six areas of need emerged and these were similar in both group These were: 1) Assistance with activities of daily living especially related to a lack of independence; 2) Social connectedness: need for social participation; 3) Financial security: worry about financial security and increased costs of health-seeking behaviours; 4) Occupational needs: desire to continue work for financial and social reasons, facilitated by flexibility of workplace conditions/environment; 5) Exercise and leisure: including limitation due to pain; 6) Transportation: limitations in ability to drive and take public transport due to mobility concerns. Many areas of need were linked; e.g. loss of employment and requiring support from family was associated with a sense of "failure" and loss of identity, as social isolation. CONCLUSIONS: This review highlights the pervasive impact of arthritis on peoples' lives, regardless of aetiology, albeit with a limited evidence base. Improved identification and targeting of non-healthcare needs of people with arthritis is likely to improve person-centred care.
34381358 Anti-inflammatory and Pro-apoptotic Effects of 18beta-Glycyrrhetinic Acid In Vitro and In 2021 18β-Glycyrrhetinic acid (18β-GA), an active component from Glycyrrhiza glabra L. root (licorice), has been demonstrated to be able to protect against inflammatory response and reduce methotrexate (MTX)-derived toxicity. This study was therefore designed to test the therapeutic possibility of 18β-GA on rheumatoid arthritis (RA) and to explore the underlying mechanism. LPS or TNF-α-induced inflammatory cell models and collagen-induced arthritis (CIA) animal models were applied in this study. Real-time quantitative PCR (RT-qPCR) was used to measure the mRNA levels of various cytokines and FOXO family members. The protein levels of molecules in the MAPK/NF-κB signaling pathway were analyzed using western blot. The cell proliferation assay and colony-forming assay were used to test the influence of 18β-GA on cell viability. The cell apoptosis assay and cell cycle assay were performed to detect the effect of 18β-GA on cell proliferative capacity by using flow cytometry. Hematoxylin and eosin (H&E) staining was performed to evaluate pathological changes after drug administration. The enzyme-linked immunosorbent assay (ELISA) was carried out for the detection of cytokines in serum. In vitro, we found that 18β-GA decreased the mRNA levels of IL-1β, IL-6, and COX-2 by inhibiting the MAPK/NF-κB signaling pathway in MH7A and RAW264.7 cell lines. Moreover, 18β-GA was able to suppress cell viability, trigger cell apoptosis, and G1 phase cell cycle arrest in our in vitro studies. 18β-GA dramatically enhanced the mRNA level of FOXO3 in both TNF-α- and LPS-induced inflammation models in vitro. Interestingly, after analyzing GEO datasets, we found that the FOXO3 gene was significantly decreased in the RA synovial tissue as compared to healthy donors in multiple microarray studies. In vivo, 18β-GA exhibited a promising therapeutic effect in a collagen-induced arthritis mouse model by alleviating joint pathological changes and declining serum levels of TNF-α, IL-1β, and IL-6. Finally, we observed that 18β-GA administration could mitigate liver damage caused by collagen or MTX. Collectively, the current study demonstrates for the first time that 18β-GA can inhibit inflammation and proliferation of synovial cells, and the underlying mechanism may be associated with its inhibition of MAPK/NF-κB signaling and promotion of FOXO3 signaling. Therefore, 18β-GA is expected to be a new drug candidate for RA therapy.
34917914 Human endogenous retroviruses (HERV) and non-HERV viruses incorporated into the human geno 2021 Genomic incorporation of viruses as human endogenous retroviruses (HERVs) are components of our genome that possibly originated by incorporating ancestral of exogenous viruses. Their roles in the evolution of the human genome, gene expression, and the pathogenesis of autoimmune diseases (ADs) and neoplastic phenomena are the subject of intense research. This review analyzes the evolutionary and virological aspects of HERVs and other viruses that incorporate their genome into the human genome and have known role in the genesis of ADs. These insights are helpful to understand further the possible role in autoimmunity genesis of HERVs, other ancestral viruses no HERVs and modern viruses with the ability to incorporate into the human genome or interact with HERVs.
34874837 The effect of exercise on patients with rheumatoid arthritis on the modulation of inflamma 2021 Nov 23 A healthy lifestyle is critical to maintaining safety and preventing rheumatic disease before reaching old age. Rheumatoid arthritis (RA) is a chronic autoimmune and systemic illness involving joint changes, including inflammation, joint pain, tiredness, elevated risk of developing coronary and heart disease, and rapid loss of muscle mass. The role of exercise in improving the inflammatory pattern has tended to focus on the latest research. However, some physical activities represent a non-pharmacological treatment strategy due to their many benefits, such as improved muscle mass, strength, and efficiency, especially in patients with RA. During exercise, skeletal muscle releases myokines, triggering a direct anti-inflammatory effect with each activity or enhancing comorbidity. The level of inflammatory biomarkers, such as tumour necrosis factor, C-reactive protein, and interleukin-6, is significantly lower for athletes and patients with RA who exercise regularly. However, understanding the precise roles of some environmental and genetic factors can help to prevent rheumatic disorders. This review highlights the influence of exercise and training on the inflammatory module in patients with rheumatic disease. More detailed data is needed to clarify the benefits of exercise in the context of RA and inflammation.
34381782 ELMO1 Regulates RANKL-Stimulated Differentiation and Bone Resorption of Osteoclasts. 2021 Bone homeostasis is a metabolic balance between the new bone formation by osteoblasts and old bone resorption by osteoclasts. Excessive osteoclastic bone resorption results in low bone mass, which is the major cause of bone diseases such as rheumatoid arthritis. Small GTPases Rac1 is a key regulator of osteoclast differentiation, but its exact mechanism is not fully understood. ELMO and DOCK proteins form complexes that function as guanine nucleotide exchange factors for Rac activation. Here, we report that ELMO1 plays an important role in differentiation and bone resorption of osteoclasts. Osteoclast precursors derived from bone marrow monocytes (BMMs) of Elmo1(-/-) mice display defective adhesion and migration during differentiation. The cells also have a reduced activation of Rac1, p38, JNK, and AKT in response to RANKL stimulation. Importantly, we show that bone erosion is alleviated in Elmo1(-/-) mice in a rheumatoid arthritis mouse model. Taken together, our results suggest that ELMO1, as a regulator of Rac1, regulates osteoclast differentiation and bone resorption both in vitro and in vivo.
34745588 Alternative care providers in rheumatoid arthritis patient care: a queueing and simulation 2021 Patients diagnosed with rheumatoid arthritis require lifelong monitoring by a rheumatologist. Initiation of the disease-modifying anti-rheumatic drug therapy within twelve weeks of the onset of symptoms is crucial to prevent joint damage and functional disability. We examine the impact of the engagement of alternate care providers (ACP) in alleviating delay due to limited rheumatologist capacity. Using queueing theory and discrete-event simulation, we model rheumatologist-only and rheumatologist-with-ACP system configurations as closed, multi-class queueing networks with class switching.Using summary data from an actual rheumatology clinic for illustration, we analyze various parameter conditions to aid clinic managers and policymakers in decisions concerning capacity allocations and feasible patient panel size that impact timeliness of care and resource utilization.Results not only confirm that a substantial increase in RA patient panel size with an ACP involved in the care of follow-up patients but also demonstrates the boundaries for feasible panel sizes and workload allocation.
32419503 A new approach to capturing pain disclosure in daily life in-person and online. 2021 Nov This feasibility study employed a new approach to capturing pain disclosure in face-to-face and online interactions, using a newly developed tool. In Study 1, 13 rheumatoid arthritis and 52 breast cancer patients wore the Electronically Activated Recorder to acoustically sample participants' natural conversations. Study 2 obtained data from two publicly available online social networks: fibromyalgia (343,439 posts) and rheumatoid arthritis (12,430 posts). Pain disclosure, versus non-pain disclosure, posts had a greater number of replies, and greater engagement indexed by language style matching. These studies yielded novel, multimethod evidence of how pain disclosure unfolds in naturally occurring social contexts in everyday life.
34912219 Impact of Non-Persistence on Healthcare Resource Utilization and Costs in Patients With Im 2021 Rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are chronic progressive immune-mediated rheumatic diseases (IMRD) that can cause a progressive disability and joint deformation and thus can impact in healthcare resource utilization (HCRU) and costs. The main outcome of the study was to assess the effect of non-persistence to treatment with subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) on HCRU costs in naïve patients with IMRD who started treatment with adalimumab, etanercept, golimumab or certolizumab pegol during 12 months after initiation of treatment. The impact of persistence and non-persistence of SC-TNFis on HCRU costs was compared between 12 months before and 12 months after initiating SC-TNFis. Persistence was defined as the duration of time from initiation to discontinuation of therapy. The study was conducted in an acute care teaching hospital in Barcelona, Spain. Data for the period between 2015 and 2018 were extracted from the hospital cost management control database. HCRU costs comprised outpatient care, outpatient specialized rheumatology care, in-patient care, emergency care, laboratory testing and other non-biological therapies. The study population included 110 naïve SC-TNFis patients, divided into the cohorts of persistent (n = 85) and non-persistent (n = 25) patients. Fifty-six percent of patients were women, with a mean (standard deviation) age of 47.6 (14.8) years. Baseline clinical features and HCRU costs over the 12 months before the index prescription were similar in the two study groups. Before-and-after differences in mean (standard deviation) HCRU costs were significantly higher in the non-persistence group as compared to the persistence group for outpatient rheumatology care (€110.90 [234.56] vs. €20.80 [129.59], p = 0.023), laboratory testing (-€193.99 [195.88] vs. -€241.3 [217.88], p = 0.025), other non-biological drugs (€3849.03 [4046.14] vs. -€10.90 [157.42], p < 0.001) and total costs (€3268.90 [4821.55] vs. -€334.67 (905.44), p < 0.001). Treatment persistence with SC-TNFis may be associated with HCRU cost savings in naïve IMRD patients. Prescribing SC-TNFis with the best long-term persistence is beneficial.
34194863 Pulmonary Alveolar Microlithiasis and Rheumatoid Arthritis: A Case Report and Review of th 2021 Pulmonary alveolar microlithiasis is a rare autosomal recessive condition that is characterized by the formation of excessive calcium phosphate microliths in the alveoli. Most patients are diagnosed in adulthood due to the slow progression of the disease. Children with this disease are asymptomatic, and changes in the lung parenchyma are usually discovered incidentally. The diagnosis is made by the combination of a positive chest imaging and histological examination. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by chronic seropositive symmetrical inflammatory polyarthritis with numerous extra-articular manifestations. It targets the lining of the synovial membranes, frequently affects females more than males, and is treated with the disease-modifying antirheumatic drugs (DMARDs). If left untreated, it leads to increased morbidity, mortality, and socioeconomic burdens. In this case, we report a 19-year-old young man who presented with clinical and radiographic features of PAM associated with RA.
33564974 There are similarities between rheumatic disease with lung involvement and COVID-19 pneumo 2022 Feb INTRODUCTION: There is considerable overlap between the clinical manifestations of covid-19 pneumonia and the acute interstitial lung disease seen in certain rheumatic disorders. In addition, pulmonary fibrosis is increasingly recognised as a potentially serious consequence of both. METHODS: This review explores this overlap of clinical features, risk factors and causation, offering insights into the immune mechanisms that contribute to both sets of disorders. RESULTS: The therapeutic role of immunosuppression and biologic agents in the treatment of covid-19 is explained in the light of this. DISCUSSION: We propose how lessons learned from the insights recently gained into each disorder can improve our insight into immunological mechanisms and application of therapeutic interventions in the other.
34988358 Therapeutic efficacy of denosumab for rheumatoid arthritis: a systematic review and meta-a 2021 OBJECTIVES: Denosumab is used for osteoporosis because it inhibits osteoclast maturation and suppresses bone resorption. Although denosumab is expected to inhibit the bone erosion in RA, its therapeutic efficacy is not well established. The aim of this study was to estimate the effects of denosumab on RA through a meta-analysis. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Web of Science and Scopus were searched for original studies providing information on BMD, joint destruction and disease activity in denosumab-treated RA. A random-effects model was used in the meta-analysis. RESULTS: Of the 367 studies identified, 18 met the selection criteria. The BMDs of the lumbar spine, total hip and femoral neck at 12 months after denosumab treatment increased by 5.27% (95% CI: 4.37, 6.18), 2.82% (2.46, 3.18) and 3.07% (2.66, 3.48), respectively. In the sensitivity analysis, age and sex tended to influence the effect of denosumab therapy on the rate of variation of BMD, but not glucocorticoid use. The changes in the modified total sharp, erosion and joint space narrowing scores at 12 months after denosumab treatment were significantly smaller with denosumab than with placebo, although the DAS did not change after denosumab treatment. CONCLUSION: Although denosumab has an inhibitory effect on the bone resorption in RA, its effects might be influenced by the age and sex of RA patients, but not by glucocorticoid use.
34209167 Exploring the Oral Microbiome in Rheumatic Diseases, State of Art and Future Prospective i 2021 Jun 30 The oral microbiome is receiving growing interest from the scientific community, as the mouth is the gateway for numerous potential etiopathogenetic factors in different diseases. In addition, the progression of niches from the mouth to the gut, defined as "oral-gut microbiome axis", affects several pathologies, as rheumatic diseases. Notably, rheumatic disorders (RDs) are conditions causing chronic, often intermittent pain affecting the joints or connective tissue. In this review, we examine evidence which supports a role for the oral microbiome in the etiology and progression of various RDs, including rheumatoid arthritis (RA), Sjogren's syndrome (SS), and systemic lupus erythematosus (SLE). In addition, we address the most recent studies endorsing the oral microbiome as promising diagnostic biomarkers for RDs. Lastly, we introduce the concepts of artificial intelligence (AI), in particular, machine learning (ML) and their general application for understanding the link between oral microbiota and rheumatic diseases, speculating the application of a possible AI approach-based that can be applied to personalized medicine in the future.
34184191 Baricitinib and the Risk of Incident Interstitial Lung Disease: A Descriptive Clinical Cas 2021 Sep OBJECTIVES: Interstitial lung disease (ILD) occurs in up to 30% of patients with rheumatoid arthritis (RA), resulting in increased morbidity and death in the absence of proven therapies. The aim of this study is to estimate the number of incident ILD cases reported through development studies with baricitinib in patients with RA. METHODS: Estimates were based on 3770 patients with RA from eight randomized clinical trials (four phase 3, three phase 2, one phase 1b) and one long-term extension study on baricitinib for which ILD was not an exclusion criterion with 12,358 patient-years of exposure (PYE). RESULTS: Twenty-one non-infectious cases of ILD were reported with an exposure-adjusted incidence rate (EAIR) of 0.17 per 100 PYE. Of the 21 cases, six were reported as serious and 15 as non-serious resulting in an incidence rate of 0.05 per 100 PYE and 0.12 per 100 PYE, respectively. There were also 11 cases caused by an infectious agent: seven serious (IR: 0.06 per 100 PYE) and four non-serious cases (IR: 0.03 per 100 PYE). CONCLUSIONS: The findings of this analysis in patients with RA treated with baricitinib are consistent with a low risk to develop non-infectious ILD during baricitinib treatment, similar to that observed with other Janus kinase inhibitors.
33719873 Corneal biomechanical parameters in systemic autoimmune diseases. 2022 Jan CLINICAL RELEVANCE: The relationship between the cornea and systemic autoimmune diseases has been demonstrated in prior studies. Corneal Visualisation Scheimpflug Technology (Corvis ST) provides a specific and detailed assessment of corneal biomechanical features, such as stiffness and elasticity. BACKGROUND: This study aims to evaluate corneal biomechanical changes in patients with systemic autoimmune diseases using Corvis ST. METHODS: This prospective study included 36 patients with ankylosing spondylitis (AS), 38 patients with rheumatoid arthritis (RA), and 36 age- and sex-matched healthy subjects. After ophthalmologic examinations Pentacam HR and Corvis ST was performed on all eyes. The mean keratometric and pachymetric data, corneal biomechanical parameters, biomechanical intraocular pressure (bIOP) were analysed. RESULTS: There was no statistically significant differences among the groups regarding age, gender, refraction, visual acuity, IOP, pachymetry and keratometry. Compared to healthy controls, the mean velocity values of applanation 1 (A1V) and 2 (A2V), deformation amplitude (DA), and corvis biomechanical index (CBI) were statistically significantly higher and stiffness parameter at first applanation (SPA1) was statistically significantly lower in AS and RA patients (all p < 0.05). In both AS and RA groups, disease duration was found to be negatively correlated with SPA1 (p = 0.043, 0.027, respectively) and positively correlated with CBI (p = 0.022, 0.020, respectively). CONCLUSION: AS and RA patients have a decreased corneal stiffness compared to healthy subjects. Disease duration seems to be correlated with these changes.