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ID PMID Title PublicationDate abstract
30997151 Re-treatment with abatacept plus methotrexate for disease flare after complete treatment w 2019 OBJECTIVES: To complete reporting of outcomes after total withdrawal of all rheumatoid arthritis (RA) therapy and re-treatment after flare in Assessing Very Early Rheumatoid arthritis Treatment study (NCT01142726). METHODS: Patients with early RA were initially randomised to double-blind, weekly subcutaneous abatacept plus methotrexate, or abatacept or methotrexate monotherapy. At month 12, patients with Disease Activity Score (DAS)28 C reactive protein (CRP) <3.2 had all RA treatments rapidly withdrawn and were observed for ≤12 months or until flare. After ≥3 months' withdrawal, patients with protocol-defined RA flare received open-label abatacept plus methotrexate for 6 months (re-treatment). RESULTS: Proportion of patients in DAS28-CRP-defined remission remained numerically higher in original abatacept plus methotrexate and abatacept arms versus methotrexate arm up to day 253 of withdrawal. At the end of the withdrawal period, few patients remained in remission across all arms: 9/73 (12.3%), 7/50 (14.0%) and 6/53 (11.3%), respectively. For patients entering re-treatment, after 6 months' re-treatment, 95/124 (76.6%) and 78/124 (62.9%) patients achieved DAS28-CRP <3.2 and <2.6, respectively; mean changes in DAS28-CRP and Health Assessment Questionnaire-Disability Index scores from re-treatment baseline were -2.87 and 0.76, respectively. Re-treatment was well tolerated; exposure-adjusted infection rates per 100 patient-years were lower with abatacept plus methotrexate during withdrawal (7.2) and re-treatment (17.2) versus initial treatment periods of months 0-6 (116.6) and 6-12 (64.6). CONCLUSIONS: Most patients flared within 6 months of therapy withdrawal and few sustained major responses for 1 year. Re-treatment with abatacept plus methotrexate was effective and well tolerated in this controlled setting.
29844591 Cystathionine-γ-lyase ameliorates the histone demethylase JMJD3-mediated autoimmune respo 2019 Aug Cystathionine-γ-lyase (CSE), an enzyme associated with hydrogen sulfide (H(2)S) production, is an important endogenous regulator of inflammation. Jumonji domain-containing protein 3 (JMJD3) is implicated in the immune response and inflammation. Here, we investigated the potential contribution of JMJD3 to endogenous CSE-mediated inflammation in rheumatoid arthritis (RA). Upregulated CSE and JMJD3 were identified in synovial fibroblasts (SFs) from RA patients as well as in the joints of arthritic mice. Knocking down CSE augmented inflammation in IL-1β-induced SFs by increasing JMJD3 expression. In addition, CSE(-/-) mice with collagen-induced arthritis (CIA) developed severe joint inflammation and bone erosion. Conversely, overexpressing CSE inhibited JMJD3 expression by the transcription factor Sp-1 and was accompanied by reduced inflammation in IL-1β-treated SFs. Furthermore, JMJD3 silencing or the administration of the JMJD3 inhibitor GSK-J4 significantly decreased the inflammatory response in IL-1β-treated SFs, mainly by controlling the methylation status of H3K27me3 at the promoter of its target genes. GSK-J4 markedly attenuated the severity of arthritis in CIA mice. In conclusion, suppressing JMJD3 expression by the transcription factor Sp-1 is likely responsible for the ability of CSE to negatively modulate the inflammatory response and reduce the progression of RA.
31315667 A single bacterium restores the microbiome dysbiosis to protect bones from destruction in 2019 Jul 17 BACKGROUND: Early treatment is key for optimizing the therapeutic success of drugs, and the current initiating treatment that blocks the progression of bone destruction during the pre-arthritic stages remains unsatisfactory. The microbial disorder in rheumatoid arthritis (RA) patients is significantly reversed with effective treatment. Modulating aberrant gut microbiomes into a healthy state is a potential therapeutic approach for preventing bone damage. RESULTS: By using metagenomic shotgun sequencing and a metagenome-wide association study, we assessed the effect of Lactobacillus casei (L. casei) on the induction of arthritis as well as on the associated gut microbiota and immune disorders in adjuvant-induced arthritis (AIA) rats. Treatment of AIA rats with L. casei inhibited joint swelling, lowered arthritis scores, and prevented bone destruction. Along with the relief of arthritis symptoms, dysbiosis in the microbiome of arthritic rats was significantly reduced after L. casei intervention. The relative abundance of AIA-decreased Lactobacillus strains, including Lactobacillus hominis, Lactobacillus reuteri, and Lactobacillus vaginalis, were restored to normal and Lactobacillus acidophilus was upregulated by the administration of L. casei to the AIA rats. Moreover, L. casei downregulated the expression of pro-inflammatory cytokines, which are closely linked to the effect of the L. casei treatment-associated microbes. Functionally, the maintenance of the redox balance of oxidative stress was involved in the improvement in the L. casei-treated AIA rats. CONCLUSION: A single bacterium, L. casei (ATCC334), was able to significantly suppress the induction of AIA and protect bones from destruction in AIA rats by restoring the microbiome dysbiosis in the gut, indicating that using probiotics may be a promising strategy for treating RA, especially in the early stage of the disease.
30944034 Inhibition of hexokinases holds potential as treatment strategy for rheumatoid arthritis. 2019 Apr 3 INTRODUCTION: Abnormal glycolytic metabolism contributes to joint inflammation and destruction in rheumatoid arthritis (RA). We examine the expression and function of hexokinases in RA and evaluate the potential of their specific inhibitor for clinical treatment. METHODS: Detection of HKs was assessed in synovial tissue by immunohistology and Western blot. SiRNA and a specific hexokinases inhibitor, lonidamine (LND), were used to evaluate the role of hexokinase-I/II (HK-I/II). Pro-inflammatory and glycolysis factors, cell viability, and apoptosis were assessed by ELISA, RT-qPCR, MTS, and flow cytometry. The clinical effects of LND on type II collagen-induced arthritis (CIA) in DBA-/1 mouse model was evaluated by scoring their clinical responses, synovitis, and cartilage destructions, and ELISA was employed to analyze the concentrations of antibody in the serum of CIA model. RESULTS: HK-I/II expression and their activities increased in the synovium of RA compared with osteoarthritis (OA). Silencing HK-I/II (siHK-I/II) or LND treatment decreased the production of pro-inflammatory factors, such as IL-6, IL-8, CXCL9, CXCL10, and CXCL11, and cell viability, but induced cell apoptosis of RASFs. The expression of TNF-α and IL-1β of macrophage in response to LPS stimulation were depressed as well after treatment with siHK-I/II or LND. Furthermore, leucocyte infiltration co-cultured with RASFs was also suppressed after inhibiting the expression or activity of HK-I/II. These anti-inflammatory effects overlapped with their anti-glycolytic activities. Treatment with LND in mice with CIA decreased the production of antibodies against IgG1, IgG2a, and IgG2b and consequently attenuated joint inflammation and destruction. CONCLUSIONS: HK-I/II contribute to shape the inflammatory phenotype of RASFs and macrophages. LND may be a potential drug in treating patients with RA.
31781682 Low-Dose Sirolimus Immunoregulation Therapy in Patients with Active Rheumatoid Arthritis: 2019 BACKGROUND: We have reported previously the insufficient absolute number or functional defects of regulatory T cells (Tregs) in patients with rheumatoid arthritis (RA), challenging conventional unspecific immunosuppressive therapy. Sirolimus, a mTOR inhibitor, is reported to allow growth of functional Tregs; here, we investigated the efficacy of low-dose sirolimus combined with conventional immunosuppressants (sirolimus immunoregulation therapy) for RA treatment with lower side effects and better tolerance. METHODS: In this nonblinded and parallel-group trial, we randomly assigned 62 patients to receive conventional glucocorticoids and immunosuppressants with or without sirolimus at a dosage of 0.5 mg on alternate days for 24 weeks in a 2 : 1 ratio. The demographic features, clinical manifestations, and laboratory indicators including peripheral blood lymphocyte subgroups and CD4(+)T subsets were compared before and after the treatment. RESULTS: Finally, 37 patients in the sirolimus group and 18 in the conventional treated group completed the 6-month study. By 24 weeks, the patients with sirolimus experienced significant reduction in disease activity indicators including DAS28, ESR, and the number of tender joints and swollen joints (p < 0.001). Notably, they had a higher level of Tregs as compared with those with conventional therapy alone (p < 0.05), indicating that sirolimus could partly restore the reduced Tregs. Concomitantly, their usage of immunosuppressants for controlling disease activity was decreased as compared with the conventional group with no difference in blood routine, and liver and renal functions both before and after the treatment of sirolimus and between the two groups (p > 0.05). CONCLUSIONS: Low-dose sirolimus immunoregulatory therapy selectively upregulated Tregs and partly replaced the usage of immunosuppressants to control disease activity without overtreatment and evaluable side effect. Further study is required using a large sample of RA patients treated with sirolimus for a longer period. This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=17245).
30504445 Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the P 2019 Feb OBJECTIVES: We explored the effects of B-cell directed therapy in subjects at risk of developing autoantibodypositive rheumatoid arthritis (RA), who never experienced inflammatory arthritis before, and explored biomarkers predictive of arthritis development. METHODS: Individuals positive for both anti-citrullinated peptide antibodies and rheumatoid factor but without arthritis were included in a randomised, double-blind, placebo-controlled study to receive a single infusion of 1000 mg rituximab or placebo. RESULTS: Eighty-one individuals received treatment and were followed up for a mean of 29.0 (0-54) months, during which 30/81 (37%) individuals developed arthritis. The observed risk of developing arthritis in the placebo-treated group was 40%, which was decreased by 55% (HR 0.45, 95% CI 0.154 to 1.322) in the rituximab-treated group at 12 months. Rituximab treatment caused a delay in arthritis development of 12 months compared with placebo treatment at the point when 25% of the subjects had developed arthritis (p<0.0001). Erythrocyte sedimentation rate and the presence of anti-citrullinated α-enolase peptide 1 at baseline were significant predictors of arthritis development. CONCLUSIONS: A single infusion of 1000 mg rituximab significantly delays the development of arthritis in subjects at risk of developing RA, providing evidence for the pathogenetic role of B cells in the earliest, prearthritis stage of autoantibody positive RA.
31848735 Effects of 1-year anti-TNF-α therapy on vascular function in rheumatoid arthritis and ank 2020 Mar Accelerated atherosclerosis, increased cardiovascular morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Vascular function, clinical and laboratory markers and the effects of anti-TNF therapy were assessed in arthritides. Fifty-three 53 patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. A significant improvement of brachial artery FMD was observed after 6 months (p = 0.004). A tendency of FMD improvement was also observed after 12 months (p = 0.065). ccIMT did not change throughout the year. PWV significantly improved after 12 months (p = 0.034). Higher baseline ccIMT (p = 0.009) and PWV (p = 0.038) were associated with clinical non-response (cNR) versus response (cR) to biologics. Multiple analysis confirmed the association of baseline ccIMT with age (p = 0.003) and cNR (p = 0.009), as well as that of baseline PWV with age at diagnosis (p = 0.022) and current chest pain (p = 0.004). Treatment itself determined the 12-month changes in FMD (p = 0.020) and PWV (p = 0.007). In a mixed cohort of RA and AS patients, TNF inhibition improved or stabilized vascular pathophysiology. Inflammation may be associated with FMD, while, among others, cNR may influence vascular function.
31926492 Correlation between Relative Expression of IL 17 and PERP in Rheumatoid Arthritis Patients 2019 Jul Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Decreased apoptosis is considered an important leading cause of autoimmune diseases. As IL17 and PERP can affect apoptosis process, they may contribute the pathogenesis and activity of RA. Objectives of this study were to investigate the possible correlation of IL 17 and PERP levels with RA pathogenesis and activity. Peripheral blood mononuclear cells (PBMCs) were isolated from fifty RA patients and fifty healthy subjects, RNA was extracted and subjected to real time PCR to detect the relative expression of IL17 and PERP. Results were correlated with RA disease activity parameters. Increased IL17 and decreased PERP mRNA expression levels were detected in patients as compared to the healthy controls (PË‚0.001) and they were positively and inversely correlated with disease activity score for 28 joints (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF). A significant negative correlation between PERP and IL-17 mRNA expression levels was found (P Ë‚0.001). In conclusion, increased level of IL 17 and decreased level of PERP may constitute two major factors in the pathogenesis and activity of RA.
29908013 Patient-Reported Disease Activity and Adverse Pregnancy Outcomes in Systemic Lupus Erythem 2019 Mar OBJECTIVE: While increased rheumatic disease activity during pregnancy has been associated with adverse pregnancy outcomes, this disease activity is typically assessed by physicians. Little is known, however, about the association between patient-reported measures of disease activity and pregnancy outcomes. The aim of our study was to evaluate this association. METHODS: Univariate and multivariable regression models were used to assess the relationship between patient- and physician-reported measures of disease activity and adverse pregnancy outcomes in 225 patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). The patients were enrolled from 2008-2016 in a prospective registry at a single academic center. RESULTS: In women with RA, patient-reported disease activity was associated with preterm birth (odds ratio [OR] 5.9 [95% confidence interval (95% CI) 1.5, 23.9]) and gestational age in weeks (β = -1.5 [95% CI -2.6, -0.4]). The physician assessment of disease activity also predicted preterm (OR 2.1 [95% CI 1.2, 3.5]), small for gestational age births (OR 1.8 [95% CI 1.03, 3.1]), and gestational age in weeks (β = -0.6 [95% CI -0.9, -0.02]). Alternatively, in women with SLE, patient-reported disease activity measures, including the Health Assessment Questionnaire, pain, or global health measures, were not associated with adverse pregnancy outcomes. However, physician measures of SLE disease activity are associated with preterm birth (OR 2.9 [95% CI 1.3, 6.3]), cesarean delivery (OR 2.3 [95% CI 1.0, 5.3]), and preeclampsia (OR 2.8 [95% CI 1.3, 6.3]). The results did not appear to be driven by lupus nephritis or antiphospholipid syndrome. CONCLUSION: For women with RA, patient-reported measures of disease activity were associated with adverse pregnancy outcomes, and thus may be useful adjuncts to physician-reported measures in identifying pregnancies at greater risk. In contrast, in SLE, while physician measures of disease activity helped predict several adverse pregnancy outcomes, no patient-reported measures were associated with adverse outcomes.
30896663 Anti-cyclic citrullinated peptide antibody is highly associated with rheumatoid factor and 2019 Mar Rheumatoid arthritis (RA) is a chronic debilitating inflammatory disease affecting mainly the joint, surrounding tissue and other extra-articular structures in the body. RA can lead to destruction of bone and cartilage which may cause severe disability and it is characterized by the presence of serum rheumatoid factor (RF). The anti-cyclic citrullinate peptide (anti-CCP) antibody is another serum biomarker used in RA diagnosis with higher sensitivity and specificity.In this cross-sectional study with retrospective record review, 159 established RA patients from Hospital Universiti Sains Malaysia (HUSM) were recruited. Enzyme-linked immunosorbent assays (ELISAs) for serum RF and anti-CCP were performed. Our goal was to evaluate the significance of anti-CCP antibody in predicting the disease activity and progression in terms of radiological and extra-articular manifestations upon diagnosis.Of the 159 RA patients included in this study, mean age was 48.3 years old and majority (n = 134; 84.3%) were female. A total of 83 (52.2%) and 99 (62.3%) patients had anti-CCP antibody and RF, respectively. Mean Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (ESR) (DAS28-ESR) score for all patients was 4.74 (medium and high disease activity). Fifty-eight (36.5%) patients had radiological defects and 49 (30.8%) patients had extra-articular involvement manifested by rheumatoid nodule, pulmonary involvement, and anemia.In terms of anti-CCP antibody association with clinical and laboratory parameters, a significant co-occurrence of RF and anti-CCP antibody (P = .002) was observed. Anti-CCP antibody was significantly associated with radiological defects in which majority of patients with such defects (n = 40/58; 68.9%) were positive for anti-CCP antibody (P = .001). However, there was no significant difference between mean and classes of disease activity score and extra-articular manifestations between different anti-CCP antibody groups. In addition, extra-articular manifestations were not associated with high disease activity upon RA diagnosisThere was a significant association between anti-CCP antibody positivity and positive RF. Radiological defects were the sole clinical parameter significantly associated with anti-CCP antibody positivity, indicating that patients positive for anti-CCP antibody should be routinely monitored for radiological defects and their onset.
30942097 Associations between IL-23R gene polymorphisms and the susceptibility of rheumatoid arthri 2019 Dec OBJECTIVE: This meta-analysis was aimed to verify the influences of interleukin 23 receptor (IL-23R) rs11209026 and rs2201841 polymorphisms on the susceptibility of rheumatoid arthritis (RA). METHODS: We searched potentially relevant studies on the relationships of IL-23R gene rs11209026 and rs2201841 polymorphisms with RA susceptibility from PubMed (Medline), CNKI and EMBASE web databases. Crude odds ratios (ORs) along with 95% confidence intervals (95% CIs) were calculated to assess the strength of association through the fixed- or random-effects model. RESULTS: Eight published articles containing 5544 RA patients and 5532 health individuals were included in our meta-analysis. In total analysis, we found IL-23R gene rs11209026 polymorphism was not related to RA susceptibility in all genetic models, but there was a significant association between rs2201841 polymorphism and RA susceptibility under G vs. A model. In stratified analysis by ethnicity, an increased RA susceptibility was detected for rs2201841 polymorphism in Caucasian group. CONCLUSION: The results of meta-analysis indicated that IL-23R gene rs2201841 polymorphism might be a susceptible factor for RA under G vs. A model, especially in Caucasian population.
31280935 Questioning a publication bias between industry-funded and non-industry-funded randomized 2020 Feb BACKGROUND: There has been a significant increase in financial support of clinical research by the pharmaceutical industry. METHODS: We performed a comprehensive systematic literature review to determine whether there is publication bias for rheumatoid arthritis (RA) studies between industry-funded and non-industry funded randomized controlled trials (RCTs), and between RCTs with positive results (PRs) and those with negative results (NRs) of FDAapproved biological and small molecule drug therapy for RA. Each RCT was classified as having either a PR or a NR, and as having received commercial funding or not. RESULTS: Most (297/349, 85.18%) of the RCTs were commercially funded. There was no significant difference in PRs or association with publication between commercially and noncommercially funded RCTs. Sample size was significantly larger in commercially funded RCTs and in those with PRs, and it was the only significant parameter that predicted publication in higher impact factor journals in the field of RA. CONCLUSION: There is no significant association between commercial funding and the publication of positive results or the publication of an RCT in higher impact factor journals.
31638308 Correlation between frailty and disease activity in patients with rheumatoid arthritis: Da 2019 Dec AIM: Frailty is defined as the degradation of physical and cognitive function in older adults. The relationship between frailty and disease activity in patients with rheumatoid arthritis is unclear. Factors related to frailty in Japanese rheumatoid arthritis patients were investigated in a cross-sectional analysis. METHODS: Of 100 patients who entered the prospective, observational Correlation research of sarcopenia, skeletal muscle and disease activity in rheumatoid arthritis (CHIKARA) study, 95 completed a frailty check list (maximal score 25), and were classified as frail (8-25 points), pre-frail (4-7 points) and normal (0-3 points). The relationship with disease activity was investigated in the frailty, pre-frailty and normal groups. Relationships between clinical variables and frailty were evaluated by univariate and multiple logistic regression analyses. RESULTS: The prevalences of frailty, pre-frailty and normal were 18.9%, 38.9% and 42.2%, respectively. The disease activity score 28 erythrocyte sedimentation rate, matrix metalloproteinase 3 and modified health assessment questionnaire were higher in the frailty group. In remission, 66.6% were normal and 6.7% had frailty, but with moderate and high disease activity, 13.3% were normal and 46.7% had frailty. On univariate analysis, factors positively related to frailty were age, locomotive syndrome, disease activity score 28 erythrocyte sedimentation rate, matrix metalloproteinase 3, use of biological disease-modifying antirheumatic drugs or targeted synthetic disease-modifying antirheumatic drugs, Steinbrocker class and modified health assessment questionnaire; and the leg muscle score and grip strength were negatively related. Matrix metalloproteinase 3 was the only independent factor on multivariate logistic analysis. In patients aged >60 years, this tendency was similar. CONCLUSIONS: Frailty was found to be related to disease activity and physical function in rheumatoid arthritis. Control of disease activity appears important to prevent frailty. Geriatr Gerontol Int 2019; 19: 1220-1225.
30511229 Validity and interpretability of the QuickDASH in the assessment of hand disability in rhe 2019 May Objective of this study is to evaluate the construct validity and the interpretability of the shortened Disability of Arm, Shoulder and Hand Questionnaire (QuickDASH) in the assessment of rheumatoid arthritis (RA) hand disability. Consecutive RA patients were assessed through the QuickDASH and other function and disease activity indices, respectively, the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the Recent-Onset Arthritis Disability questionnaire (ROAD). For each patient were evaluated the tender and swollen 28-joints counts. Interpretability was defined determining cut-off points of impairment in accordance to the Simplified Disease Activity Index (SDAI) definition of disease activity states. A total of 440 patients (89 men and 351 women, mean age of 57.0 ± 12.7 years) were enrolled. Following the SDAI definition, 98 patients (22.3%) resulted in REM, 115 subjects (26.1%) in LDA, 74 patients (16.8%) in MDA, and 153 subjects (34.8%) in HDA. Mean QuickDASH differed significantly between patients classified as remission (REM), low disease activity (LDA), moderate disease activity (MDA), or high disease activity (HDA) (p < 0.001). High correlations were found comparing QuickDASH to composite indices of disease activity and of physical health function: of special interest are the correlations between the comparable dimension of the QuickDASH and the ROAD Upper Extremity Function (rho = 0.876; p < 0.001). The cut-off points for functional categories (SDAI categories as external criterion) resulted: no impairment ≤ 13, 13 < low impairment ≤ 18.5, 18.5 < moderate impairment ≤ 31.5, and high impairment > 31.5. QuickDASH is useful in clinical practice, for its ease of administration, and positively correlates with the disease activity. It may be a surrogate for evaluating upper extremity impairment, disability index and disease control in RA patients.
30466715 Applicability of trials in rheumatoid arthritis and osteoarthritis: A systematic review an 2019 Jun OBJECTIVES: To evaluate whether elderly people and women are adequately represented in randomized controlled trials (RCT) in rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Four systematic searches in MEDLINE yielded RCT in RA and OA on any intervention published in 2016 and 2017 and population-based studies (PBS) in RA and OA published between 2013 and 2017. Random effects meta-analyses estimated the pooled proportion of elderly people (defined as being ≥ 65 years old), the mean age, its standard deviation (SD), and the proportion of women stratified by disease (RA and OA) and study type (RCT and PBS). Stratified estimates were subsequently compared. RESULTS: 265 RCT comprising 51,240 participants and 53 PBS comprising 523,630 participants were included. In both RA and OA, RCT included lower proportions of elderly people than PBS: RA -0.18 (95% confidence interval -0.22 to -0.13); OA -0.20 (-0.30 to -0.09); had lower mean ages: RA -5.2 years (-6.8 to -3.5); OA -4.7 years (-7.5 to -2.0); and smaller SD: RA -1.9 years (-2.6 to -1.3); OA -2.7 years (-4.2 to -1.2); (all comparisons: p ≤ 0.001). Proportions of women were comparable in RCT compared to PBS in both RA and OA. CONCLUSIONS: While women are adequately represented in RA and OA trials, the elderly are underrepresented, probably limiting applicability of current evidence to this growing subgroup. It is urgent to improve the inclusion of elderly people in clinical trials and study age as a determinant for outcome.
30868232 Thinking beyond pannus: a review of retro-odontoid pseudotumor due to rheumatoid and non-r 2019 Oct Retro-odontoid pseudotumor, or mass-like retro-odontoid soft tissue thickening, is an uncommon but important imaging finding that may be associated with rheumatoid arthritis, crystal deposition diseases, as well as non-inflammatory conditions such as cervical degenerative changes and mechanical alterations. Retro-odontoid pseudotumor is commonly associated with atlantoaxial microinstability or subluxation. MRI and CT have an important role in the detection and diagnosis of retro-odontoid pseudotumor. However, due to a wide range of imaging characteristics and ambiguous etiology, it is a frequently misunderstood entity. The purpose of this article is to review relevant anatomy of the craniocervical junction; describe various imaging appearances, pathophysiology and histology in both rheumatoid and non-rheumatoid etiologies; and discuss differential diagnosis of retro-odontoid pseudotumor in order to help guide clinical management.
31699813 Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid 2020 Jan OBJECTIVE: The causality and pathogenic mechanism of microbiome composition remain elusive in many diseases, including autoimmune diseases such as rheumatoid arthritis (RA). This study aimed to elucidate gut microbiome's role in RA pathology by a comprehensive metagenome-wide association study (MWAS). METHODS: We conducted MWAS of the RA gut microbiome in the Japanese population (n (case)=82, n (control)=42) by using whole-genome shotgun sequencing of high depth (average 13 Gb per sample). Our MWAS consisted of three major bioinformatic analytic pipelines (phylogenetic analysis, functional gene analysis and pathway analysis). RESULTS: Phylogenetic case-control association tests showed high abundance of multiple species belonging to the genus Prevotella (e.g., Prevotella denticola) in the RA case metagenome. The non-linear machine learning method efficiently deconvoluted the case-control phylogenetic discrepancy. Gene functional assessments showed that the abundance of one redox reaction-related gene (R6FCZ7) was significantly decreased in the RA metagenome compared with controls. A variety of biological pathways including those related to metabolism (e.g., fatty acid biosynthesis and glycosaminoglycan degradation) were enriched in the case-control comparison. A population-specific link between the metagenome and host genome was identified by comparing biological pathway enrichment between the RA metagenome and the RA genome-wide association study results. No apparent discrepancy in alpha or beta diversities of metagenome was found between RA cases and controls. CONCLUSION: Our shotgun sequencing-based MWAS highlights a novel link among the gut microbiome, host genome and pathology of RA, which contributes to our understanding of the microbiome's role in RA aetiology.
30995934 The agreement between ultrasound-determined joint inflammation and clinical signs in patie 2019 Apr 17 BACKGROUND: Ultrasound (US) is sensitive for detecting joint and tendon inflammation in patients with rheumatoid arthritis (RA). So far, which grade of abnormalities on US corresponds to clinical manifestations is unclear. This study aimed to investigate the agreement between US-detected joint inflammation and clinical signs (joint swelling and tenderness). METHODS: In this cross-sectional study, 22 joints of the wrists and hands were, respectively, evaluated by physical examination (PE) and ultrasound in RA patients. Gray scale (GS) and power Doppler (PD) of synovitis, detected by ultrasound, were graded by semi-quantitative scoring systems (0-3). Tenosynovitis and peritendinitis were assessed qualitatively (0/1). RESULTS: A total of 258 consecutive RA patients were included, with median disease duration of 57 months and mean Disease Activity Score based on 28 joints (DAS28)-ESR/DAS28-CRP of 4.47/3.99. In a total of 5676 joints assessed, the overall concordance rate between positive clinical signs and ultrasound-determined joint inflammation was fair (κ = 0.365, p < 0.01). In wrists, joint tenderness showed higher κ coefficient (κ = 0.329, p < 0.01) with ultrasound-determined joint inflammation than swelling (κ = 0.263, p < 0.01); however, swelling showed higher κ coefficient (κ = 0.156-0.536, p < 0.01) with ultrasound-determined joint inflammation than tenderness (κ = 0.061-0.355, p < 0.01) in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. Synovitis had consistently higher agreement with tenderness and swelling than tenosynovitis/peritendinitis. Tenderness and swelling had the highest κ coefficient with GS ≥ 1 synovial hyperplasia in most MCP and PIP joints, while with GS ≥ 2 synovial hyperplasia in wrists. For all 22 joints, PD ≥ 1 synovitis had the highest κ coefficient with clinical tenderness and swelling. CONCLUSIONS: Synovitis had better agreement with clinical signs than tenosynovitis/peritendinitis. Joint swelling showed better agreement with US-determined inflammation than tenderness for MCP and PIP joints, while the opposite for wrists. Both tenderness and swelling are more likely to correspond to GS ≥ 2 for wrists, GS ≥ 1 for MCP and PIP joints, and PD ≥ 1 for any joint.
31026097 α-Mangostin promotes apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes 2019 Sep α-Mangostin (α-M) is a commonly used traditional medicine with various biological and pharmacological activities. Our study aimed to explore the effects and mechanism of α-M in regulating apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). α-M of 10 to 100 μM was used to treat RA-FLS for 24 hours, followed by measuring cell viability and apoptosis. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinases was detected. Treatment of α-M promoted apoptosis and reduced viability of RA-FLS in a dose-dependent manner. The mitochondrial membrane potential in RA-FLS was remarkably reduced by α-M treatment, accompanied by the cytochrome c accumulation in the cytosol and increased activities of caspase-3 and caspase-9. Moreover, we found that α-M treatment promoted ROS production and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. The proapoptotic activity of α-M in RA-FLS was markedly reversed by the co-induction with the ERK1/2 inhibitor LY3214996 or ROS scavenger N-acetyl-l-cysteine. In conclusion, our studies found that α-M had remarkable proapoptotic activities in RA-FLS, which is regulated by the induction of ROS accumulation and ERK1/2 phosphorylation. α-M may thus have potential therapeutic effects for rheumatoid arthritis.
31881377 Up-regulation of miR-365 promotes the apoptosis and restrains proliferation of synoviocyte 2020 Feb BACKGROUND: There is growing evidence of the ability of microRNAs (miRs) in rheumatoid arthritis (RA), thus our objective was to discuss the impact of miR-365 on the apoptosis and proliferation of synoviocytes in mice with RA by targeting IGF1 and mediating the PI3K/AKT/mTOR pathway. METHODS: RA model mice was induced by type II collagen and freund's adjuvant. The successfully modeled mice were injected with normal saline, miR-365 mimics, miR-365 inhibitors or their controls. TUNEL assay was adopted to detect apoptosis in synovial tissues, and expression of IL-1β and IL-6 in serum and synovial tissues was measured by ELISA and RT-qPCR. Mouse synoviocytes were isolated and cultured in vitro and identified by experiments. Cells were transfected with miR-365 mimics, IGF1 siRNA, or their controls to verify the role of miR-365 and IGF1 in cell vitality, proliferation and apoptosis of synoviocytes. RESULTS: Upregulation of miR-365 increased the number of TUNEL positive cells, depressed arthritis index, X-ray imaging score, and the expression of IL-1β and IL-6. High expression of miR-365 and low expression of IGF1 restrained the proliferation and facilitated apoptosis of synoviocytes. MiR-365 inhibited the expression of IGF1 and inhibited the activation of the PI3K/AKT/mTOR pathway. CONCLUSION: Our study presents that up-regulation of miR-365 drives on apoptosis and restrains proliferation of synoviocytes in RA through downregulation of IGF1 and the inhibition of the PI3K/AKT/mTOR pathway. Thus, miR-365 may be a potential candidate for treatment of RA.