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ID PMID Title PublicationDate abstract
32977590 Role of Infections in the Pathogenesis of Rheumatoid Arthritis: Focus on Mycobacteria. 2020 Sep 23 Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease characterized by chronic erosive polyarthritis. A complex interaction between a favorable genetic background, and the presence of a specific immune response against a broad-spectrum of environmental factors seems to play a role in determining susceptibility to RA. Among different pathogens, mycobacteria (including Mycobacterium avium subspecies paratuberculosis, MAP), and Epstein-Barr virus (EBV), have extensively been proposed to promote specific cellular and humoral response in susceptible individuals, by activating pathways linked to RA development. In this review, we discuss the available experimental and clinical evidence on the interplay between mycobacterial and EBV infections, and the development of the immune dysregulation in RA.
32923448 Association of Use of Rehabilitation Services With Development of Dementia Among Patients 2020 Objectives: Rheumatoid arthritis (RA) was found to trigger the higher risk of dementia. Limited information, however, is available on whether the use of rehabilitation services (RS), an integral part of healthcare programs, can lessen dementia risk for RA subjects. The aim of this study was to determine the relationship of RS use to the development of dementia in RA patients. Methods: We identified 2,927 newly diagnosed patients with RA, 20-70 years of age between 1998 and 2007, from a national health insurance database. 965 patients from this sample received RS, and 1,962 patients were designated as a control group (non-RS users). Patients were followed to the end of 2012 to identify dementia incident as the end point. Cox proportional hazards regression was performed to calculate the hazard ratio (HR) of dementia risk associated with the use of RS. Results: During the study period, 388 patients with RS and 1,224 controls developed dementia, representing incidence rate of 75.46 and 115.42 per 1,000 person-years, respectively. After adjusting for potential confounders, RS was found to significantly reduce dementia risk, with the adjusted HR of 0.60 (95% confidence interval [CI] = 0.53-0.67). Those who used the high intensity of RS (≧15 courses) had the greatest benefit. Conclusions: Integrating RS into the conventional treatment may reduce the sequent risk of dementia for RA patients.
32844379 Dose Adjustment of Methotrexate Administered Concomitantly with Golimumab for Rheumatoid A 2020 Dec INTRODUCTION: The combination of methotrexate (MTX) with biological disease-modifying antirheumatic drugs (bDMARDs) is a recommended treatment option for rheumatoid arthritis (RA) patients showing an inadequate response to MTX monotherapy. However, the adequate dose of MTX, especially in long-term treatment with bDMARDs/MTX combination therapy, remains under-addressed. Since RA patients require long-term treatment, we examined the effects of using golimumab (GLM) in the long run as well as its persistency and associated factors. METHODS: We used the Japan Medical Data Center Inc. (JMDC) administrative claims data of 489 patients receiving GLM therapy for calculating the persistency in patients with constant, reduced, or escalated MTX dosing. The factors associated with GLM persistency were assessed using Cox proportional hazard modeling, controlling for the dose adjustment of concomitant MTX, age, sex, RA disease period, and the initial dose of GLM or concomitant MTX during GLM/MTX combination therapy. RESULTS: During GLM/MTX combination therapy, up to 52% of patients were reported to experience dose adjustments of concomitant MTX treatment (i.e., dose reduction and escalation in 34% and 18% of patients, respectively). Persistency was similar in the MTX dose-reduction patients and the MTX dose-constant patients. In the Cox proportional hazard model, no significant differences were observed in association with GLM persistency, including with respect to MTX dose adjustment. CONCLUSIONS: GLM prescription was continued in 80% or more (1 year) and 50% or more (3 years) of RA patients receiving reduced concomitant MTX dosing, suggesting that MTX dose adjustment (including MTX reduction) could be considered in GLM/MTX combination therapy.
32581804 Identifying Patient Access Barriers for Tumor Necrosis Factor Alpha Inhibitor Treatments i 2020 INTRODUCTION: Although there is a significant utilization gap of biologic medicines in the EU, many studies estimate equity in patient access to biopharmaceuticals only based on their availability on the national list of reimbursed medicines. Hidden access barriers may facilitate financial sustainability of pharmaceuticals in less affluent EU countries; however, they have rarely been documented in scientific publications. Our objective was to explore these access barriers for tumor necrosis factor (TNF) alpha inhibitors in rheumatoid arthritis (RA) in five Central and Eastern European countries. METHODS: A detailed interview guide was developed based on multi-stakeholder workshops and a targeted literature review. In each participant country 3-3-3-3 interviews with payers, rheumatologists, patients/patient representatives, and industry representatives were conducted. Responses were aggregated at a country level and validated by primary investigators in each country. RESULTS: Limited number of RA centers and consequently significant travelling time and cost for patients in distant geographical areas, uneven budget allocation among centers, limited capacity of nurses, narrowed patient population in national financial protocols compared to international clinical guidelines in initiating or continuing biologics, high administrative burden in prescribing biologics and limited health literacy of patients were the most relevant barriers to timely patient access in at least three participant countries. CONCLUSION: Assessing only the availability of TNF alpha inhibitors on the national list of reimbursed medicines provides limited information about real-world patient access to these medicines. Revealing hidden access barriers may contribute to initiate policy actions which could reduce inequity in patient access.
32214841 ADAM17 Genetic Variants and the Response of TNF-α Inhibitor in Rheumatoid Arthritis Patie 2020 PURPOSE: TNF-α is a transmembrane protein which requires cleavage by ADAM17 in order to act systemically. The activation of ADAM17 to generate soluble TNF‑α results in an increased inflammatory activity. We hypothesized that variants spanning the ADAM17 gene contribute towards the observed variation in patient response defined by the number of changes in TNF‑α inhibitors. PATIENTS AND METHODS: Seven single-nucleotide polymorphisms (SNPs) of ADAM17 in 63 patients with rheumatoid arthritis who received TNF-α inhibitors were analyzed: rs57467365, rs62117540, rs117645314, rs6432013, rs532704607, rs117179141, and rs12692386. Univariate and multivariate regression analysis were employed to investigate the independent predictable factors for changes in TNF-α inhibitors. RESULTS: ADAM17 rs117645314 and rs117179141 showed significant association with the number of changes in TNF-α inhibitors. Patients with GA in rs117645314 and AT in rs117179141 had significantly higher chance of two or more changes of TNF-α inhibitors than those with wild homozygous alleles. Multivariate analysis showed that rs117179141 explained 5.7% of the 23.8% variability in TNF-α inhibitor response. CONCLUSION: This study showed that the number of changes in TNF-α inhibitor is associated with ADAM17 SNPs.
33331330 [Angioimmunoblastic T-cell lymphoma with fever, arthritis and skin pigmentation: A case re 2020 Dec 18 Angioimmunoblastic T-cell lymphoma is a rare T-cell lymphoma. The clinical manifestations are not specific. In addition to the common clinical manifestations of lymphomas such as fever, weight loss, night sweats and lymphadenopathy, it may also have skin rashes, arthritis, multiple serous effusions, eosinophilia and other systemic inflammatory or immune symptoms. The lymphoma cells of angioimmunoblastic T-cell lymphoma originates from follicular helper T cells, and the follicular structure of lymph nodes disappears. In the tumor microenvironment, in addition to tumor cells, there are a large number of over-activated immune cells, such as abnormally activated B cells, which produce a series of systemic inflammation or immune-related symptoms. This disease is rare and difficult to diagnose. This article reports a 36-year-old female. She got fever, joint swelling and pain, skin pigmentation, accompanied by hepatomegaly, splenomegaly, lymphadenopathy, anemia and other multiple-systems manifestations. The clinical manifestations of this patient were similar to autoimmune diseases such as adult onset Still's disease, rheumatoid arthritis, and systemic sclerosis, which made the diagnosis difficult. At the beginning of the disease course, the patient got arthritis and fever. And her white blood cells were significantly increased. Adult onset Still's disease should be considered, but her multiple-systems manifestations could not be explained by adult onset Still's disease. And her arthritis of hands should be distinguished with rheumatoid arthritis. However, the patient's joint swelling could get better within 3-7 days, and there was no synovitis and bone erosion on joint imaging examination. The rheumatoid factor and anti-CCP antibody were negative. The diagnostic evidence for rheumatoid arthritis was insufficient. The patient's skin pigmentation and punctate depigmentation were similar to those of systemic sclerosis. But the patient had no Raynaud's phenomenon, and her sclerosis-related antibody was negative. The diagnostic evidence for systemic sclerosis was also insufficient. After 3 years, she was finally diagnosed with angioimmunoblastic T-cell lymphoma by lymph node biopsy aspiration. This case suggests that the clinical manifestations of angioimmunoblastic T-cell lymphoma are diverse, and some symptoms similar to immune diseases may appear. When the patient's clinical symptoms are atypical and immune diseases cannot explain the patient's condition, and further evidence should be sought to confirm the diagnosis.
33355913 How to Define Boolean Low Disease Activity in Rheumatoid Arthritis: Experience from a Larg 2021 Mar INTRODUCTION: The aim of this work is to propose Boolean-defined low disease activity (LDA) and to test its utility in rheumatoid arthritis (RA). METHODS: We used data from a longitudinal academic clinical database of RA in Peking University First Hospital over a decade. The initial proposal of Boolean-defined LDA was proposed with ascending thresholds from 2 to 5 in steps of 1 (referred to as Boolean-LDA2/3/4/5). Agreement and residual swollen joint count (SJC) pattern with the index-based [Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI)] LDA was analyzed. To confirm discovery, we randomly classified RA patients in a 3:2 ratio into either analysis cohort or validation cohort. RESULTS: In total, 4881 visits of 672 patients were included in the analysis cohort. Of these visits, the frequencies of achieving LDA were 71.9% (SDAI), 73.6% (CDAI), 52.8% (Boolean-LDA2), 65.2% (Boolean-LDA3), 73.5% (Boolean-LDA4), and 80.7% (Boolean-LDA5). High consistency and similar SJC pattern with SDAI-LDA or CDAI-LDA were observed in Boolean-LDA3 (kappa = 0.796, 0.771). Further analysis found meeting SDAI-LDA but not Boolean-LDA3 was largely attributable to higher patient's global assessment (PGA) scores (62.9%). In further modification of Boolean-LDA3, better agreement with SDAI-LDA or CDAI-LDA was reached when exclusively increasing PGA cutoffs to 4.0, 4.5 or replacing PGA by evaluator's global assessment (EGA) with cutoff to 3.0. These findings were further replicated in randomly generated validation cohort of 449 patients with 3306 clinic visits. CONCLUSIONS: Using cutoff of 3 to Boolean-LDA provides great clinical utility with index-based LDA, especially when exclusively increasing PGA cutoffs to 4.0, 4.5 or replacing PGA by EGA with cutoffs to 3.0. This may deserve being considered in clinical practice.
33042681 Rheumatoid Arthritis Does Not Negatively Impact Outcomes of Patients Admitted for Atrial F 2020 Sep 4 Objectives This study aimed to compare the outcomes of patients primarily admitted for atrial fibrillation (AF) with and without a secondary diagnosis of rheumatoid arthritis (RA). The primary outcome of interest was inpatient mortality. Hospital length of stay (LOS), total hospital charges, and odds of undergoing ablation and pharmacologic cardioversion were the secondary outcomes of interest. Methods Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 databases. The NIS is the largest hospitalization database in the United States (US). The NIS was searched for hospitalizations for adult patients with AF as principal diagnosis with and without RA as secondary diagnosis using the International Classification of Diseases, 10th Revision (ICD-10) codes. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. Results There were over 71 million discharges in the combined 2016 and 2017 NIS database. Out of 821,630 AF hospitalizations, 17,020 (2.1%) had RA. Hospitalizations for AF with RA had 0.18 days' decrease in adjusted mean LOS (p=0.014), and lower total hospital charges ($38,432 vs $39,175, p=0.018) compared to those without RA. AF hospitalizations with RA had similar inpatient mortality [1.1% vs 0.91%, adjusted odds ratio (AOR): 0.90, 95% CI: 0.63-1.27, p=0.540] and odds of undergoing ablation (3.5% vs 4.2%, AOR: 1.1, 95% CI: 0.87-1.30, p=0.549) and pharmacologic cardioversion (0.38% vs 0.38%, AOR: 1.00, 95% CI: 0.53-1.89, p=0.988) compared to those without RA. Conclusions Patients admitted for AF with coexisting RA were found to have lesser adjusted mean LOS and lower total hospital charges compared to those without RA. However, inpatient mortality and the odds of undergoing ablation and pharmacologic cardioversion were similar between both groups.
32429264 Inflammatory and Oxidative Stress Markers-Mirror Tools in Rheumatoid Arthritis. 2020 May 15 Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease, associated with significant morbidity, mainly due to progressive damage and consequent disability. Oxidative stress is an important part of RA pathophysiology, as in autoimmune disease the interaction between immune response and endogenous/exogenous antigens subsequently induce the production of reactive oxygen species. The oxidative stress process seems to be positively strongly correlated with inflammation and accelerated joint destruction. We were asking ourselves if the oxidative stress biomarkers are the mirror tools of disease activity, outcome, and inflammation level in a group of RA patients under standard or biological therapy compared to healthy age-matched controls. In order to do this, the oxidative stress damage biomarkers (lipids peroxide and protein carbonyl level), antioxidant defense capacity, and pro-inflammatory status of plasma were quantified. In this study, we took into account the complete picture of RA diseases and assessed, for the first time, the inflammatory level in correlation with the oxidative stress level and antioxidant capacity of RA patients. Our results revealed that protein oxidation through carbonylation is significantly increased in RA groups compared to controls, and both protein carbonyl Pcarb and thiobarbituric acid reactive substance (TBARS) are reliable markers of ROS damage. Therefore, it is unanimous that neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio ( MLR), platelet/lymphocyte ratio (PltLR) correlated with Pcarb, and TBARS can provide a view of the complex phenomenon represented by proteins/lipids damage, key contributors to disease outcome, and an increased awareness should be attributed to these biomarkers.
32743529 Antibody response to homologous epitopes of Epstein-Barr virus, Mycobacterium avium subsp. 2020 BACKGROUND: Improved knowledge of different biomarkers is crucial for early diagnosis of rheumatic diseases and to provide important insights for clinical management. In this study, we evaluated the seroreactivity of patients with different connective tissue diseases (CTDs) (rheumatoid arthritis, RA; systemic lupus erythematosus, SLE; systemic sclerosis, SSc; and Sjogren's syndrome, SSj) to interferon regulatory factor 5 (IRF5) peptide and homologs derived from Epstein-Barr virus (EBV) and Mycobacterium avium subsp. paratuberculosis (MAP). Antigen-induced arthritis (AIA) experiments have been performed in control and IRF5 conditional knockout mice to reinforce the hypothesis that antibodies generated against the three homologous peptides are cross-reactive. METHODS: Reactivity against wild-type (wt) and citrullinated (cit) IRF5 (IRF5(424-434)), MAP (MAP_4027(18-32)) and EBV (BOLF1(305-320)) peptides were tested by indirect ELISA in sera from 100 RA patients, 54 patients with other CTDs (14 SLE, 28 SSc and 12 SSj) and 100 healthy subjects (HCs). Antibody responses to the same wt peptides have been tested in AIA mouse sera after immunization with complete Freud's adjuvant (CFA) and methylated bovine serum albumin (mBSA) to induce arthritis in the knee joint. RESULTS: BOLF1, MAP_4027 and IRF5 peptides triggered different antibody responses in CTD diseases with a stronger reactivity in RA (p=0.0001). Similar trends were observed in AIA mice with significantly higher reactivity after 7 days from induction of arthritis. We also found statistically significant differences in antibody responses between SSc and HCs for BOLF1 (p=0.003), MAP_4027 (p=0.0076) and IRF5 (p=0.0042). Peripheral reactivity to cit peptides was lower compared to their wt counterparts, except for cit-MAP_4027(18-32), which induced stronger responses in RA than wt-MAP_4027(18-32) (46% vs. 26%, p=0.0170). Conclusion(s): Our results show differential antibody responses to BOLF1, MAP_4027 and IRF5 peptides among CTDs, highlighting their potential as diagnostic biomarkers in these diseases. Experiments performed in IRF5 conditional knockout mice support the hypothesis of cross-reactivity between the investigated homologous antigens.
32786678 Joint Synovial Fluid Metabolomics Method to Decipher the Metabolic Mechanisms of Adjuvant 2020 Sep 4 Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is mainly characterized by joint lesions and permanent loss of joint function. To discover the metabolic characteristics of RA and the underlying mechanisms in treatment with geniposide (GE), untargeted metabolomic analysis based on hydrophilic interaction liquid chromatography coupled to high-resolution mass spectrometry (HILIC-HRMS) was performed using the joint synovial fluid samples from adjuvant arthritis (AA) rats. Microdialysis (MD) was utilized to collect the dialysate samples precisely from the articular cavity of AA rats. Multivariate statistical analysis was then conducted to discover the metabolite changes induced by AA and to differentiate GE-related biomarkers. The mass spectrometry data are available on the Chorus website (https://chorusproject.org/pages/index.html) with the data set identifier 1680. The results showed that 20 metabolites differed significantly between AA rats and normal rats. GE treatment recovered the altered levels of the 13 metabolites mentioned above, such as palmitoylethanolamide (PEA), Cer (d18:0/22:0), and PC (18:1(11Z)/16:1(9Z)), and normalized glycerophospholipid metabolism. As evidenced by western blotting, the changes in PEA levels adjusted by GE were associated with the down-regulated expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA) in synovial tissues. Taken together, the elucidation of metabolic changes of joint synovial fluid and how this is influenced by GE will promote future therapeutic interventions of RA.
32009119 Pharmacological Properties of JTE-952, an Orally Available and Selective Colony Stimulatin 2020 Colony stimulating factor 1 (CSF1) receptor (CSF1R) is a receptor protein-tyrosine kinase specifically expressed in monocyte-lineage cells, such as monocytes and macrophages. In this study, we characterized the pharmacological properties of an azetidine compound, JTE-952 ((2S)-3-{[2-({3-[4-(4-cyclopropylbenzyloxy)-3-methoxyphenyl]azetidine-1-yl}carbonyl)pyridin-4-yl]methoxy}propane-1,2-diol), which is a novel CSF1R tyrosine kinase inhibitor. JTE-952 potently inhibited human CSF1R kinase activity, with a half maximal inhibitory concentration of 11.1 nmol/L, and inhibited the phosphorylation of CSF1R in human macrophages and the CSF1-induced proliferation of human macrophages. It also inhibited human tropomyosin-related kinase A activity, but only at concentrations 200-fold higher than that required to inhibit the activity of CSF1R in inducing the proliferation of human macrophages. JTE-952 displayed no marked inhibitory activity against other kinases. JTE-952 potently inhibited lipopolysaccharide-induced proinflammatory cytokine production by human macrophages and in whole blood. JTE-952 (≥3 mg/kg given orally) also significantly attenuated the CSF1-induced priming of lipopolysaccharide-induced tumor necrosis factor-alpha production in mice and arthritis severity in a mouse model of collagen-induced arthritis. Taken together, these results indicate that JTE-952 is an orally available compound with potent and specific inhibitory activity against CSF1R, both in vitro and in vivo. JTE-952 is a potentially clinically useful agent for various human inflammatory diseases, including rheumatoid arthritis.
33116399 Dexamethasone-Loaded Thermosensitive Hydrogel Suppresses Inflammation and Pain in Collagen 2020 PURPOSE: To overcome negative adverse effects and improve therapeutic index of dexamethasone (Dex) in rheumatoid arthritis (RA), we developed a novel sustained release formulation-intra-articular injectable dexamethasone-loaded thermosensitive hydrogel (DLTH) with chitosan-glycerin-borax as carrier for the remission of inflammation and pain. The focus of this article is to explore both anti-inflammatory and pain-relieving effects of DLTH joint injection in bovine type-II collagen-induced arthritis (CIA) rats. METHODS: Wistar rats were randomized into three groups, including the normal group (n=6), the model group (n=6) and the DLTH group (n=10). Joint injection of DLTH (1mg/kg Dex per rat) was injected on day 12 in the DLTH group twice a week for three weeks. Clinical signs of body weight, paw swelling and arthritis scores, histologic analysis, hind paw mechanical withdrawal threshold (MWT), plantar pressure pain threshold (PPT) were taken into consideration. Serum contents of IL-17A, prostaglandin E2 (PGE2), prostacyclin 2 (PGI2) and prostaglandin D2 (PGD2), real-time polymerase chain reaction (PCR) analysis of inflammatory factors and pain-related mediators in synovium and dorsal root ganglia (DRG), Western blotting of NF-κB in synovium were all evaluated. RESULTS: Paw swelling, arthritis scores and joint inflammation destruction were all attenuated in the DLTH-treated group. Results showed that DLTH not only down-regulated serum IL-17A, but also mRNA levels of inflammatory factors and NGF, and key proteins contents of the NF-κB pathway in synovium. Increases of MWT and PPT in DLTH-treated rats elucidated pain-reducing effects of DLTH. Elevated serum PGD2 levels and declines of serum PGE2 and PGI2, and inflammatory and pain-related genes in DRGs in the DLTH group were also recorded. CONCLUSION: These data elucidated that DLTH joint injection impeded synovial inflammation processes through down-regulating transcription activity of NF-κB pathway, and intra-articular DLTH may aid in the regulation of RA pain through regulating inflammation and pain conduction process.
33246122 Dendropanax dentiger (Harms) Merr. root and its major constituents exert therapeutic effec 2021 Mar 1 ETHNOPHARMACOLOGICAL RELEVANCE: The root of Dendropanax dentiger (Harms) Merr. is a pivotal folk Chinese medicine against rheumatoid arthritis (RA) with no scientific validation. AIM OF THE STUDY: This study was conducted to explore the anti-RA effect of the D. dentiger extract on complete Freund's adjuvant-induced arthritis (AIA) in rats and identified its major bio-constituents. MATERIALS AND METHODS: Dendropanax dentiger roots extracts (127.5, 255.0 and 510.0 mg/kg, once daily) were orally at day 7 post-administration adjuvant and lasting for 22 days. The therapeutic effects of D. dentiger roots extract on AIA rats were investigated by body weight growth, arthritis score, thymus and spleen indices, and histopathological analysis. Moreover, the levels of rheumatoid factor (RF), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17, cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and matrix metalloproteinase-2 (MMP-2) were also evaluated. Finally, the major constituents were isolated and identified from D. dentiger roots extract with COX-2 inhibitory and antioxidant activities. RESULTS: Dendropanax dentiger roots extract remarkably alleviated the histological lesions of knee joint, increased body weight growth, decreased arthritis score, and reduced thymus and spleen indices in model rats. In parallel, the levels of RF, CRP, TNF-α, IL-1β, IL-6, IL-17, COX-2, 5-LOX and MMP-2 were observably downregulated, while the levels of IL-4 and IL-10 were prominently upregulated in D. dentiger roots extract-treated rats. Meanwhile, 14 compounds were isolated and identified from D. dentiger roots extract, and four phenol derivatives (1, 4, 6 and 7) exhibited remarkable COX-2 inhibitory and antioxidant activities. CONCLUSIONS: Dendropanax dentiger roots extract possessed persuasive anti-RA effect may be partly responsible for phenol derivatives via modulation of inflammatory biomarkers, and supports the traditional folk use of D. dentiger in China.
33089070 Cardiovascular risk knowledge in patients of South Asian origin living with rheumatoid art 2020 BACKGROUND: South Asians have a higher risk of cardiovascular disease (CVD). Rheumatoid arthritis (RA) increases the risk of premature atherosclerosis. We investigated whether there was a substantial difference in the level of CVD risk knowledge among patients of South Asian origin with RA in India and in the UK. METHODS: In this cross-sectional survey, patients of South Asian origin with RA from India and the UK were recruited from secondary care settings. Data were collected via Heart Disease Fact Questionnaire-Rheumatoid Arthritis (HDFQ-RA), a validated self-completion questionnaire. The HDFQ-RA was translated into Hindi and piloted among patients from South Asian background before use. Additionally, clinical and demographic data was collected. RESULTS: Among 118 patients from each country, 84% were female and they had similar age, education level, employment status and co-morbidities. Patients from India had longer disease duration (5.5 years versus 4.1 years (p = 0.012) whereas those from the UK had higher disease activity score (4.0 + 0.8 versus 3.1 + 0.7, p < 0.01). Regarding modifiable risk factors for CVD only 51.2% from India and 51.3% in the UK were aware of them. However, awareness of the link between RA and increased risk of CVD was even more limited (32.8% in India and 34.4% in UK). CONCLUSION: Patients of South Asians origin with RA from both countries had limited knowledge about CVD risk. There is a need to educate them about CVD risk during consultation, as this will result in better outcomes.
32912833 Sexual Health and Dysfunction in Patients With Rheumatoid Arthritis: A Cross-sectional Sin 2020 Dec INTRODUCTION: An increased risk of sexual health problems is seen among patients with chronic illnesses. The background is likely to be multifactorial, but it remains poorly understood. AIM: To investigate the sexual health and functioning of patients with rheumatoid arthritis (RA) and to examine gender differences, general population comparisons, and possible somatic, psychological, and disease-specific determinants. METHODS: A cross-sectional study using a digital questionnaire distributed among 380 patients diagnosed with RA in a Danish university hospital outpatient setting. MAIN OUTCOME MEASURE: A range of patient-reported outcomes were obtained, including scores from the validated rating scale Changes in Sexual Functioning Questionnaire. Furthermore, individual medical record information was collected. RESULTS: A total of 329 patients (250 women and 79 men) were included (age range: 25-73 years; mean age: 57.2 years). The Changes in Sexual Functioning Questionnaire scoring indicated an overall sexual dysfunction in 33.8% of men and 58.1% of women.More than one-third (37.6%) of patients felt that RA had made their sex life more complicated, and 32.4% feared that this might someday be the case. In total, 29.2% patients had experienced sexual problems due to their RA treatment. Of the respondents who experienced RA-related fatigue, 46.5% reported that this impacted negatively on their sexual activity. The risk of one or more sexual health adversities was significantly correlated with female gender, older age, moderate or severe depression, moderate to moderately high loneliness, more than 2 comorbidities, and a fatigue score above 75 out of 100 on a visual analogue scale. Compared to the general population, significantly fewer patients with RA considered their sex life important, and significantly fewer patients appraised their current sex life as good or very good. Moreover, significantly more women with RA (32.1%) than women from the general population (15.7%) had not had any sex life during the past year. A vast majority of patients with RA (93.5% of women and 85.5% of men) had not discussed sexual issues with a health-care professional during the last 5 years. Of all, 32.5% would like health-care professionals to address sexual topics in the consultation occasionally. CONCLUSION: Sexual dysfunction is highly prevalent in patients with RA, but the problems are not regularly addressed in consultations provided by the rheumatology department. Bay LT, Graugaard C, Nielsen DS, et al. Sexual Health and Dysfunction in Patients With Rheumatoid Arthritis: A Cross-sectional Single-Center Study. Sex Med 2020;8:615-630.
32942924 Arthropathy in hereditary haemochromatosis segregates with elevated erythrocyte mean corpu 2021 Mar Objective: To evaluate the relationship between erythrocyte parameters and the presence or absence of arthritis in HFE C282Y homozygous hereditary haemochromatosis (HH) subjects compared to control groups of non-HH subjects with arthritis.Method: Erythrocyte and arthritis parameters [mean corpuscular volume (MCV) and mean cell haemoglobin (MCH)] were obtained from consecutive HH subjects (n = 119) who were referred for initial evaluation and management. For comparison, MCV and MCH values were collected from randomly selected non-HH subjects with rheumatoid arthritis (n = 100) and osteoarthritis (n = 100), consisting of equal numbers of men and women. Two other comparison groups comprised 16 men and women who were heterozygous for C282Y with arthritis, and 38 non-HH subjects with type 2 polyarticular osteoarthritis (T2POA).Results: MCV values were significantly higher in HH subjects with arthritis (95 ± 0.56 fL) than in HH subjects without arthritis (92.75 ± 0.50 fL, p = 0.037). HH subjects with or without arthritis demonstrated a higher mean MCV than the control groups of non-HH osteoarthritis (90.12 ± 0.46 fL, p < 0.001) and non-HH rheumatoid arthritis (90.94 ± 0.57 fL, p < 0.001). HH subjects with arthritis also demonstrated a higher MCV than heterozygous C282Y subjects with arthritis (93.18 ± 1.55 fL, p = 0.025) and non-HH subjects with a similar pattern of arthritis, notably T2POA (91.13 ± 0.50 fL, p < 0.01). An MCV of ≥ 97.85 fL provided a likelihood ratio of 2.2 for development of arthritis in HH subjects.Conclusion: This study demonstrated a relationship between elevated MCV and arthritis in incident cases of HH.
32290250 Interleukin 26 Skews Macrophage Polarization Towards M1 Phenotype by Activating cJUN and t 2020 Apr 10 Interleukin 26 (IL-26) is a new member of the IL-10 family that is highly expressed in rheumatoid arthritis (RA). However, the functions of IL-26 produced by macrophages in RA have not been elucidated. In the present work, we evaluated the effects and the mechanisms of IL-26 on M1 and M2 macrophage differentiation. Human or mouse macrophage cells were treated with lipopolysaccharides (LPS), interferon gamma (IFNγ), or IL-4 alone or concurrently treated with IL-26 to monitor M1 or M2 macrophage subtypes. The expression level of M1 or M2 macrophage genes was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The molecular mechanisms of downstream signaling activation during differentiation were investigated by immunoblotting assay. Our results found that IL-26 promoted macrophage cells from CD80(+) M1 macrophage differentiation, not from the CD206(+) M2 phenotype. The messenger RNA of M1-type macrophage markers tumor necrosis factor alpha (TNFα) and inducible nitric oxide synthase (iNOS) was up-regulated in the IL-26-treated group. Also, the M1-related proinflammatory cytokines TNFα and IL-6 were induced after IL-26 stimulation. Interestingly, IL-10, a cytokine marker of M2 macrophage, was also elevated after IL-26 stimulation. Moreover, the M1-like macrophage stimulated by IL-26 underwent cJUN, nuclear factor kappa B (NF-κB), and signal transducer and activator of transcription 1 (STAT1) activation. Our findings suggested the role of IL-26 in synovial macrophages of active rheumatoid arthritis and provided a new insight into IL-26 as a candidate therapeutic target in rheumatoid arthritis.
32518584 Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet 2020 BACKGROUND: Rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLSs) play important roles in pathogenesis of rheumatoid arthritis (RA). Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, is a potentially effective therapy for RA, but its underlying mechanism is unclear. In this study, we explore the effects of WJT on human RA-FLSs and the underlying molecular mechanism. METHODS: The major components of WJT were determined using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Cell proliferative ability was evaluated by CCK-8, colony formation assay, and EdU incorporation assay. Cell apoptotic capacity was examined by caspase-3 and caspase-9 activity test. Protein levels of Bax and Bcl-2 were investigated by western blotting. High-throughput sequencing and bioinformatics analysis were conducted to screen and identify targeted genes, followed by identification by qRT-PCR and western blotting. RESULTS: In this study, we have identified 346 compounds in WJT. Our results showed that WJT inhibited the RA-FLSs proliferation, and promoted apoptosis in a dose- and time-dependent manner. More importantly, 184 differentially expressed genes (DEGs) has been screened after WJT treatment based on DEGSeq2 and 278 DEGs was identified by DEGSeq2 combined with WGCNA. Then, 10 hub genes were identified based on two different analyses, while the expression levels of only SMC3, THOC1, BUB1, and STAG2 were decreased after WJT treatment, which was identical to the sequencing profiles. CONCLUSIONS: WJT exerted its anti-proliferation and pro-apoptosis effects possibly through suppressing the expression of SMC3, THOC1, BUB1, and STAG2 in RA-FLSs. Thus, therapeutics targeting these genes may be a promising strategy for rescuing RA.
32206633 Examining the relationship between rheumatoid arthritis, multimorbidity and adverse health 2020 Jan BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by articular inflammation and systemic complications. Multimorbidity (the presence of two or more long-term health conditions) is highly prevalent in people with RA but the effect of multimorbidity on mortality and other health-related outcomes is poorly understood. OBJECTIVE: To determine what is known about the effect, if any, of multimorbidity on mortality and health-related outcomes in individuals with RA. DESIGN: Systematic review of the literature. The following electronic medical databases will be searched: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, The Cochrane Library and Scopus. Included studies will be quality appraised using the Quality in Prognostic Studies tool developed by the Cochrane Prognosis Methods Group. A narrative synthesis of findings will be undertaken and meta-analyses considered, if appropriate. This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols 2015 guidelines, ensuring the quality of the review. CONCLUSIONS: Understanding the influence of multimorbidity on mortality and other health-related outcomes in RA will provide an important basis of knowledge with the potential to improve future clinical management of RA. PROSPERO registration number: CRD42019137756.