Browse

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

ID PMID Title PublicationDate abstract
33950757 Association between interleukin-1 alpha rs1800587 polymorphism and rheumatoid arthritis: A 2021 Apr No consistent results have been reached on the relationship of interleukin-1 (IL-1) rs1800587 polymorphism with the susceptibility to rheumatoid arthritis (RA) so far. Therefore, the current meta-analysis was designed to thoroughly review relevant studies, in order to examine the relationship of IL-1A rs1800587 polymorphism with RA risk. Electronic databases were retrieved for literature regarding the relationship between IL-1A rs1800587 polymorphism and RA vulnerability according to the inclusion and exclusion criteria. Stata 12.0 software was adopted to examine the enrolled literature. Meanwhile, odds ratio (OR) and corresponding 95% confidence intervals (95% CI) were used to evaluate the association. A total of seven case-control researches (3267 patients and 2960 healthy controls) were eventually enrolled into the current meta-analysis. Our data indicated no correlation of IL-1A rs1800587 polymorphism with RA risk (TT vs CC: OR = 0.90, 95% CI = 0.73-1.11; TC vs CC: OR = 1.02, 95% CI = 0.78-1.34; Dominant model: OR = 1.04, 95% CI = 0.80-1.35; Recessive model: OR = 1.91, 95% CI = 0.74-1.12). Similarly, no association was found in subgroup analysis stratified by ethnicity. Our findings indicated no relationship between IL-1A rs1800587 polymorphism and RA vulnerability.
33211602 Risk of Rheumatoid Arthritis in Patients with Endometriosis: A Nationwide Population-Based 2021 Aug Background: Abnormalities in the immune system of endometriosis has been demonstrated and may reflect the chronic inflammatory response or the autoimmune reaction to the presence of ectopic endometrial tissue. Rheumatoid arthritis (RA) is a chronic inflammatory joint disease of an autoimmune nature. The study aimed to investigate the risk of incident RA in patients with endometriosis. Materials and Methods: A total of 17,913 patients with endometriosis and 17,913 unaffected controls matched by age, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed RA were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of RA incidence rate between patients with endometriosis and unaffected controls. Results: Patients with endometriosis were associated with an increased risk of incident RA compared with unaffected controls after adjusting for age, CCI score, and hormonal and surgical treatments (3.56 vs. 1.30 per 10,000 person-years, HR: 3.71, 95% CI: 2.91-5.73). Among these adjusted variables, hormonal and surgical treatments were treated as time-dependent covariates. Stratification analyses also revealed similar risk associations linking endometriosis to subsequent RA in all stratified age and CCI score subgroups (adjusted HR all >1, although not all were significant) Conclusions: Patients with endometriosis was associated with an increased risk of incident RA. Additional prospective studies that take into account genetic vulnerability and environmental exposures are warranted to confirm this relationship.
33415451 Factors that influence biological survival in rheumatoid arthritis: results of a real-worl 2021 Jun We aim to explore real-world biological survival stratified for discontinuation reason and determine its influenceability in rheumatoid arthritis (RA) patients. Data from the local pharmacy database and patient records of a university hospital in the Netherlands were used. RA patients who started a biological between 2000 and 2020 were included. Data on age, anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) status, presence of erosions, gender, body mass index, time to first biological, biological survival time, use of csDMARDs, and discontinuation reasons were collected. Of the included 318 patients, 12% started their first biological within 6 months after diagnosis. The median time to first biological was 3.6 years (95% CI, 1.0-7.2). The median survival of the first- and second-line biological was respectively 1.7 years (95% CI, 1.3-2.2) and 0.8 years (95% CI, 0.5-1.0) (p = 0.0001). Discontinuation reasons for the first-line biological were ineffectiveness (47%), adverse events (17%), remission (16%), pregnancy (30%), or patient preference (10%). Multivariable Cox regression analyses for discontinuation due to inefficacy or adverse events showed that concomitant use of csDMARDs (HR = 1.32, p < 0.001) positively while RF positivity negatively (HR = 0.82, p = 0.03) influenced biological survival. ACPA positivity was associated with the inability to discontinue biologicals after achieving remission (HR = 1.43, p = 0.023). Second-line TNF inhibitor survival was similar between patients with a primary and secondary non-response on the first-line TNF inhibitor (HR = 1.28, p = 0.34). Biological survival diminishes with the number of biologicals used. Biological survival is prolonged if patients use csDMARDs. RF was negatively associated with biological survival. ACPA was negatively associated with the inability to discontinue biologicals after achieving remission. Therefore, tailoring treatment based upon autoantibody status might be the first step towards personalized medicine in RA. Key Points • Prolonged biological survival is a surrogate for treatment effectiveness; however, an increasing amount of patients will taper treatment due to remission, and factors influencing biological survival based on separate reasons for discontinuation have not been explored. • We found that combining a biological DMARD with a conventional synthetic DMARD increases biological DMARD survival. Rheumatoid factor is negatively associated with biological survival. Anti-citrullinated protein antibody is negatively associated with the inability to discontinue the biological when remission was reached. • The first step towards personalized medicine might be tailoring of treatment based upon autoantibody status.
34042306 Incident Rheumatoid Arthritis in HIV Infection: Epidemiology and Treatment. 2021 Dec OBJECTIVE: To assess the incidence, presentation, and management of rheumatoid arthritis (RA) in patients with HIV, including the use of disease-modifying antirheumatic drugs (DMARDs) in this immunosuppressed population. METHODS: Patients included in this study were from the Veterans Aging Cohort Study, a longitudinal cohort of veterans with HIV and age-, race-, and site-matched uninfected veterans. We identified all patients who had ≥1 rheumatologist-generated International Classification of Diseases, Ninth Revision (ICD-9) or Tenth Revision (ICD-10) code for RA and whose serum samples were tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. To further confirm the diagnosis of RA, medical charts were reviewed to verify whether patients met the American College of Rheumatology/European Alliance of Associations for Rheumatology 2010 criteria for RA. We recorded DMARD use and adverse effects during the first contiguous course of treatment (i.e., >6 months of no interruption in DMARD treatment). RESULTS: This study included 56,250 patients with HIV and 116,944 uninfected individuals over 2,384,541 person-years. Of the 2,748 individuals in this cohort who were reviewed for a diagnosis of RA based on ICD-9 or ICD-10 codes, incident RA was identified in 215 individuals, including 21 patients with HIV. The incidence rate ratio of RA for patients with HIV compared to uninfected individuals was 0.29 (95% confidence interval 0.19-0.48). Most of the patients diagnosed as having RA (88%) were seropositive for RA-associated autoantibodies (RF and/or anti-CCP). However, high autoantibody titers were less frequent in RA patients with HIV compared to RA patients without HIV. In total, 5% of RA patients with HIV (1 of 21) had both high titers of anti-CCP and high titers of RF, compared to 41% of uninfected individuals (81 of 194). DMARDs were prescribed in 71% of RA patients with HIV (15 of 21) compared to 94% of RA patients without HIV (183 of 194). There was no indication that the DMARD safety profile was worse among RA patients with HIV who were prescribed DMARDs (n = 10 assessed) compared to RA patients without HIV who were prescribed DMARDs (n = 158 assessed). CONCLUSION: In this cohort, incident RA was less common in patients with HIV compared to uninfected individuals. Moreover, compared to RA patients without HIV, the seropositivity rate and titers of RA-specific autoantibodies were lower among RA patients with HIV, and those with HIV were prescribed DMARDs less frequently than those without HIV.
34682415 Outcomes of Scarf and Akin Osteotomy with Intra-Articular Stepwise Lateral Soft Tissue Rel 2021 Oct 12 BACKGROUND: The effectiveness of scarf and Akin osteotomy with intra-articular lateral soft tissue release for the correction of hallux valgus (HV) in patients with rheumatoid arthritis (RA) has not been elucidated. METHODS: A total of 36 feet in 28 patients with RA who had scarf and Akin osteotomy with intra-articular stepwise lateral soft tissue release between 2015 and 2020 at a single institute were investigated retrospectively, with a mean follow-up period of 32.0 ± 16.9 months. Radiographic evaluations including the HV angle, intermetatarsal angle, and sesamoid position were performed preoperatively and postoperatively. Clinical outcomes were assessed using the Japanese Society of Surgery of the Foot (JSSF) hallux scale and self-administered foot evaluation questionnaire (SAFE-Q). RESULTS: The procedure resulted in significant HV correction, with a recurrence rate of 13.9%. The JSSF scale and all five SAFE-Q subscale scores significantly improved (p < 0.05), with no major complications. More than 90% of cases achieved adequate lateral soft tissue release without sacrificing the adductor tendon of the hallux. CONCLUSIONS: Intra-articular stepwise lateral soft tissue release in combination with scarf and Akin osteotomy provided satisfactory radiographic and patient-reported outcomes for the correction of HV in patients with RA with minimum lateral soft tissue release.
34496567 Quantitative Proteomic Analysis of Synovial Tissue Reveals That Upregulated OLFM4 Aggravat 2021 Oct 1 Tandem mass tag (TMT)-coupled liquid chromatography coupled with tandem mass spectrometry is a powerful method to investigate synovial tissue protein profiles in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Protein was isolated from synovial tissue samples of 22 patients and labeled with a TMT kit. Over 500 proteins were identified as the differential expression protein on comparing RA and OA synovial tissue, including 239 upregulated and 271 downregulated proteins. Data are available via ProteomeXchange with identifier PXD027703. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that the majority participated in the developmental processes and protein processing in the endoplasmic reticulum. Olfactomedin 4 (OLFM4), a secreted glycoprotein, in joint inflammation of RA was explored. OLFM4 was upregulated in RA synovial tissue samples. In fibroblast-like synoviocytes (FLS), inflammation cytokines, TNF-α, interleukin (IL)-1β, and LPS can upregulate OLFM4. After OLFM4 knockdown under TNF-α stimulation, RA FLS proliferation was inhibited and the expression of CXCL9, CXCL11, and MMP-1 was decreased. Overall, the RA synovial tissue protein expression profile by proteomic analysis shows some unique targets in RA pathophysiology, and OLFM4 in FLS plays an important role in RA joint inflammation. OLFM4 can be a promising therapeutic target in RA synovial tissue.
33538611 Successful discontinuation of biological disease-modifying antirheumatic drugs in patients 2021 Jul OBJECTIVES: To analyze the proportion of successful biological disease-modifying antirheumatic drugs (bDMARDs) discontinuation and related factors in patients with rheumatoid arthritis (RA) in clinical settings. METHODS: Among 1775 RA patients who started bDMARDs between 2003 and 2012, 43 patients with DAS28-ESR <3.2 at the time of bDMARD discontinuation were extracted. Patients were divided into two groups (bio-free success: BS and bio-free failure: BF groups) based on bDMARD usage and disease activity 1 year after discontinuation. We evaluated the proportion of bio-free success and assessed factors related to bio-free success. RESULTS: Twenty-five patients (58.1%: BS group) maintained discontinuation of bDMARDs and DAS28-ESR <3.2 at 1 year after discontinuation. The median DAS28-ESR at bDMARD initiation was lower in the BS group than in the BF group (3.95 vs 5.04; p = .04). The BS group experienced a larger decrease in average glucocorticoid (GC) dose during bDMARD use than the BF group (-3.0 mg/day vs 0 mg/day; p = .01). CONCLUSION: bDMARDs were discontinued without flare up of RA in 58.1% of patients with RA in clinical settings. A lower DAS28-ESR at initiation and reduction of GC dose before discontinuation of bDMARD were important factors associated with bio-free success.
34096076 Fibroblast pathology in inflammatory joint disease. 2021 Jul Rheumatoid arthritis is an immune-mediated inflammatory disease in which fibroblasts contribute to both joint damage and inflammation. Fibroblasts are a major cell constituent of the lining of the joint cavity called the synovial membrane. Under resting conditions, fibroblasts have an important role in maintaining joint homeostasis, producing extracellular matrix and joint lubricants. In contrast, during joint inflammation, fibroblasts contribute to disease pathology by producing pathogenic levels of inflammatory mediators that drive the recruitment and retention of inflammatory cells within the joint. Recent advances in single-cell profiling techniques have transformed our ability to examine fibroblast biology, leading to the identification of specific fibroblast subsets, defining a previously underappreciated heterogeneity of disease-associated fibroblast populations. These studies are challenging the previously held dogma that fibroblasts are homogeneous and are providing unique insights into their role in inflammatory joint pathology. In this review, we discuss the recent advances in our understanding of how fibroblast heterogeneity contributes to joint pathology in rheumatoid arthritis. Finally, we address how these insights could lead to the development of novel therapies that directly target selective populations of fibroblasts in the future.
34607792 Baseline predictors of different types of treatment success in rheumatoid arthritis. 2022 Feb OBJECTIVE: To perform a comprehensive analysis on predictors of achieving disease activity outcomes by change, response and state measures. METHODS: We used data from three rheumatoid arthritis (RA) trials (one for main analysis, two for validation) to analyse the effect of patient and disease characteristics, core set measure and composite indices on the achievement of different outcomes: response outcomes (% of patients achieving a relative response margin); state outcomes (remission or low disease activity, LDA) and change outcomes (numerical change on metric scales). RESULTS: We included patients from the ASPIRE trial (for analysis) and from the ATTRACT and GO-BEFORE trials (for validation). While lower disease activity components at baseline-except acute phase reactants-were associated with achievement of state outcomes (such as LDA by the Simplified Disease Activity Index, SDAI), higher baseline values were associated with change outcomes (such as SDAI absolute change). A multivariate analysis of the identified predictors of state outcomes identified best prediction by a combination of shorter disease duration, male gender and lower disease activity. For prediction of response, no consistently significant predictors were found, again, with exception of C reactive protein, for which higher levels at baseline were associated with better responses. CONCLUSION: Prediction of treatment success is limited in RA. Particularly in early RA, prediction of state targets can be achieved by lower baseline levels of diseases activity. Gender and disease duration may improve the predictability of state targets. In clinical trials, included populations and choice of outcomes can be coordinated to maximise efficiency from these studies.
34526144 Depression is associated with increased disease activity and higher disability in a large 2021 Sep 15 INTRODUCTION: Depression is a quite common comorbidity in patients with rheumatoid arthritis (RA) and is thought to influence its severity. This study aims to estimate, in a large cohort of Italian patients with RA, the prevalence of depression and to investigate the clinical correlates of depression in terms of disease activity and disability. METHODS: This is a cross-sectional study enrolling 490 outpatients with RA (80% female, mean age 59.5). The Hospital Anxiety and Depression Scale (HADS) was used to assess the presence of depression with a cut-off of 11. We collected data about disease activity and disability with DAS28, TJC-68, PhGA, PGA, VAS, DAS28, SDAI, CDAI and HAQ. RESULTS: Prevalence of depression was 14.3% (95% CI: 11-17%). Depressed patients, when compared with not depressed ones, were found to have higher scores for TJC-68 (p = 0.011), PhGA (p = 0.001), PGA (p = 0.001), VAS (p = 0.001), DAS28 (p = 0.007), SDAI (p = 0.001), CDAI (p = 0.001) and HAQ (p = 0.001). Out of the 70 depressed patients, 30 subjects, already known to be depressed in the past, were still depressed at the time of the assessment, with only 11 (15.7%) under antidepressants. A multivariate analysis showed that male sex, higher PGA score, use of antidepressants and higher HAQ score were significantly associated with an increased risk of depression. CONCLUSIONS: Our study shows that depression is common in RA and may affect its activity mainly via an alteration in the perception of the disease. Although its important implications, depression is still under-diagnosed and its management is inadequate.
33990888 Efficacy and safety of jakinibs in rheumatoid arthritis: a systematic review and meta-anal 2021 Oct OBJECTIVES: To assess the efficacy and safety of jakinibs for the treatment of active rheumatoid arthritis (RA) in patients with an inadequate response or intolerance to conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). METHODS: A systematic search was conducted in PubMed, Embase, and the Cochrane Library. Randomized placebo-controlled trials (RCTs) of jakinibs in RA patients were eligible. The effective outcome was RA improvement to reach an American College of Rheumatology 20%/50%/70% (ACR20/50/70) response rate at weeks 12 and 24 after treatment. The safety outcomes included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and discontinuations due to adverse events, infections, and serious infections. RESULTS: Twenty-eight randomized, double-blind, controlled trials including 14,500 patients were included. At both weeks 12 and 24, the pooled analysis suggested effective treatment with jakinibs, represented as an increased clinical response of ACR20, ACR50, and ACR70. Subgroup analysis based on different types of jakinibs demonstrated that only peficitinib treatment had no impact on the clinical response of ACR50 or ACR70 at week 12. Jakinibs were associated with an increased incidence of infections at week 12 and TEAEs and infections at week 24. No increase in the risk of SAEs, discontinuations due to adverse events, or serious infections was observed in comparisons between treatment with jakinibs and treatment with placebo in these patients. CONCLUSIONS: Jakinibs are efficacious and well tolerated in RA patients up to 24 weeks, although they are associated with an increased risk of infectious complications. Key Points • ACR20/50/70 in patients treated with jakinibs was significantly higher than those in patients treated with placebo. • No difference in ACR50/70 was observed in patients with RA treated with peficitinib and placebo. • Jakinibs are beneficial and well tolerated in RA treatment.
34584402 Umbilical Cord Mesenchymal Stem Cell Therapy for Regenerative Treatment of Rheumatoid Arth 2021 Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology with a high rate of disability. Traditional treatments for RA remain a challenging issue. For example, nonsteroidal anti-inflammatory drugs (NSAIDs) have no therapeutic effects on joint destruction, and the prominent side effects include gastrointestinal symptoms. RA is characterized by recurrence and bone attrition. Therefore, regenerative medicine and the use of umbilical cord mesenchymal stem cell (UC-MSC) therapies have recently emerged as potential options. UC-MSCs are multifunctional stem cells that are present in neonatal umbilical cord tissue and can differentiate into many kinds of cells, which have broad clinical application prospects in the tissue engineering of bone, cartilage, muscle, tendon, ligament, nerve, liver, endothelium, and myocardium. Moreover, UC-MSCs have advantages, such as convenient collection of materials and no ethical disputes; thus, these cells have attracted increasing attention from researchers. However, there are few clinical studies regarding UC-MSC therapy for RA. In this paper, we will review traditional drugs for RA treatment and then focus on UC-MSC therapy for RA, including preclinical and clinical UC-MSC applications for RA patients in the context of regenerative medicine. Finally, we will summarize the challenges and perspectives of UC-MSCs as a potential therapeutic strategy for RA. This review will help to design and discover more potent and efficacious treatments for RA patients and aid in advancing this class of cell therapy.
34344706 Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate 2022 Apr OBJECTIVE: To evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX). METHODS: In this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study. RESULTS: A total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (70.4%) than placebo (25.9%) (p<0.0001 for both comparisons). There were significant differences in all secondary efficacy endpoints between OKZ-treated arms and placebo. Treatment-emergent serious adverse events (TESAEs) were reported by more patients in the OKZ groups compared with placebo. Infections were the most common TESAEs. No subjects developed neutralising antidrug antibodies. CONCLUSIONS: Treatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens. Safety was as expected for this class of agents. Low immunogenicity was observed. Trial registration number NCT02760368.
33447032 Topical Nano-Vesicular Spanlastics of Celecoxib: Enhanced Anti-Inflammatory Effect and Dow 2021 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that underlies chronic inflammation of the synovial membrane. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat RA. However, a long list of adverse events associated with long-term treatment regimens with NSAIDs negatively influences patient compliance and therapeutic outcomes. AIM: The aim of this work was to achieve site-specific delivery of celecoxib-loaded spanlastic nano-vesicle-based delivery system to the inflamed joints, avoiding systemic administration of large doses. METHODOLOGY: To develop spanlastic nanovesicles for transdermal delivery of celecoxib, modified injection method was adopted using Tween 80 or Brij as edge activators. Entrapment efficiency, vesicle size, ex vivo permeation, and morphology of the prepared nano-vesicles were characterized. Carbopol-based gels containing the selected formulations were prepared, and their clarity, pH, rheological performance, and ex vivo permeation were characterized. Celecoxib-loaded niosomes and noisome-containing gels were developed for comparison. The in vivo efficacy of the selected formulations was evaluated in a rat model of Freund's complete adjuvant-induced arthritis. Different inflammatory markers including TNF-α, NF-кB and COX-2 were assessed in paw tissue before and after treatment. RESULTS: The size and entrapment efficiency of the selected spanlastic nano-vesicle formulation were 112.5 ± 3.6 nm, and 83.6 ± 2.3%, respectively. This formulation has shown the highest transdermal flux and permeability coefficient compared to the other investigated formulations. The spanlastics-containing gel of celecoxib has shown transdermal flux of 6.9 ± 0.25 µg/cm(2)/hr while the celecoxib niosomes-containing gel and unprocessed celecoxib-loaded gel have shown 5.2 ± 0.12 µg/cm(2)/hr and 0.64 ± 0.09 µg/cm(2)/hr, respectively. In the animal model of RA, the celecoxib-loaded spanlastics-containing gel significantly reduced edema circumference and significantly suppressed TNF-α, NF-кB and COX-2 levels compared to the niosomes-containing gel, the marketed diclofenac sodium gel, and unprocessed celecoxib-loaded gel. CONCLUSION: The spanlastic nano-vesicle-containing gel represents a more efficient site-specific treatment for topical treatment of chronic inflammation like RA, compared to commercial and other conventional alternatives.
34959772 Effect of Anti-Inflammatory Diets on Pain in Rheumatoid Arthritis: A Systematic Review and 2021 Nov 24 Various nutritional therapies have been proposed in rheumatoid arthritis, particularly diets rich in ω-3 fatty acids, which may lead to eicosanoid reduction. Our aim was to investigate the effect of potentially anti-inflammatory diets (Mediterranean, vegetarian, vegan, ketogenic) on pain. The primary outcome was pain on a 10 cm visual analogue scale. Secondary outcomes were C-reactive protein levels, erythrocyte sedimentation rate, health assessment questionnaire, disease activity score 28, tender/swollen joint counts, weight, and body mass index. We searched MEDLINE (OVID), Embase (Elsevier), and CINAHL for studies published from database inception to 12 November 2021. Two authors independently assessed studies for inclusion, extracted study data, and assessed the risk of bias. We performed a meta-analysis with all eligible randomized controlled trials using RevMan 5. We used mean differences or standardized mean differences and the inverse variance method of pooling using a random-effects model. The search retrieved 564 unique publications, of which we included 12 in the systematic review and 7 in the meta-analysis. All studies had a high risk of bias and the evidence was very low. The main conclusion is that anti-inflammatory diets resulted in significantly lower pain than ordinary diets (-9.22 mm; 95% CI -14.15 to -4.29; p = 0.0002; 7 RCTs, 326 participants).
33549125 Mesenchymal stem cell-originated exosomal lncRNA HAND2-AS1 impairs rheumatoid arthritis fi 2021 Feb 6 BACKGROUND: Long non-coding RNA heart and neural crest derivatives expressed 2-antisense RNA 1 (HAND2-AS1) was found to be elevated in rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLSs). However, whether HAND2-AS1 functions as an exosomal lncRNA related to mesenchymal stem cells (MSCs) in RA progression is unknown. METHODS: The expression of HAND2-AS1, microRNA (miR)-143-3p, and tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) was detected using quantitative real-time polymerase chain reaction and Western blot. Cell proliferation, apoptosis, migration, and invasion were detected using cell counting kit-8, flow cytometry, and wound healing and transwell assays. The levels of tumor necrosis factor-α (TNF-α) and interleukins (IL)-6 were analyzed using enzyme-linked immunosorbent assay. The level of phosphorylated-p65 was examined by Western blot. The binding interaction between miR-143-3p and HAND2-AS1 or TNFAIP3 was confirmed by the dual-luciferase reporter and RIP assays. Exosomes were isolated by ultracentrifugation and qualified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. RESULTS: HAND2-AS1 was lowly expressed in RA synovial tissues, and HAND2-AS1 re-expression suppressed the proliferation, motility, and inflammation and triggered the apoptosis in RA-FLSs via the inactivation of NF-κB pathway. Mechanistically, HAND2-AS1 directly sponged miR-143-3p and positively regulated TNFAIP3 expression, the target of miR-143-3p. Moreover, the effects of HAND2-AS1 on RA-FLSs were partially attenuated by miR-143-3p upregulation or TNFAIP3 knockdown. HAND2-AS1 could be packaged into hMSC-derived exosomes and absorbed by RA-FLSs, and human MSC-derived exosomal HAND2-AS1 also repressed above malignant biological behavior of RA-FLSs. CONCLUSION: MSC-derived exosomes participated in the intercellular transfer of HAND2-AS1 and suppressed the activation of RA-FLSs via miR-143-3p/TNFAIP3/NF-κB pathway, which provided a novel insight into the pathogenesis and treatment of RA.
34887290 Certolizumab-induced lichenoid eruption in a patient with rheumatoid arthritis. 2021 Dec 9 Certolizumab is a monoclonal antibody against tumour necrosis factor-alpha (TNF-α) commonly used in rheumatologic conditions such as rheumatoid arthritis. Skin rashes are an uncommon side effect with few cases of lichenoid drug eruption reported in the literature. We describe a patient with rheumatoid arthritis who presented 6 weeks after initiating certolizumab pegol. Physical examination showed pink-to-violaceous papules on her upper and lower extremities. Biopsy confirmed a lichenoid drug eruption. The medication was discontinued and she was treated with topical steroids and a calcineurin inhibitor, with resolution of her lesions. Clinicians should be cognizant of such adverse reactions to TNF-α inhibitors and keep drug-induced lichenoid eruptions on the differential. Lichenoid eruptions induced by certolizumab pegol may affect the skin and/or mucous membranes. While most cases occur within weeks to months of starting therapy, eruptions may occur years after treatment initiation, underscoring the importance of a thorough review of medications.
34351954 Clinical relevance for circulating cold-inducible RNA-binding protein (CIRP) in patients w 2021 BACKGROUND: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disease in which danger-associated molecular patterns (DAMPs)-mediated inflammasome activation seems to be involved in the disease pathogenesis. Cold-inducible RNA-binding protein (CIRP) belongs to a family of cold-shock proteins that respond to cellular stress and has been identified as a DAMP that triggers the inflammatory response. The aim of this study is to investigate the clinical significance of serum CIRP levels in AOSD. METHODS: Serum samples were obtained from 44 patients with active AOSD or 50 patients with rheumatoid arthritis (RA), 20 patients with systemic lupus erythematosus (SLE), and 15 healthy control patients (HCs). Serum levels of CIRP and IL-18 were determined using enzyme-linked immunosorbent assay. Results were compared among AOSD patients, RA patients, SLE patients and HCs. Results were also analyzed according to the clinical features of AOSD. RESULTS: Serum CIRP levels were significantly higher in AOSD patients compared with RA patients (median: 9.6 ng/mL, IQR [5.7-14.4] versus 3.2 ng/mL, IQR [1.9-3.8]; p < 0.001) and with HCs (2.8 ng/mL, [IQR; 1.4-4.9], p < 0.001). There was a significant positive correlation between serum CIRP levels and AOSD disease activity score (Pouchot's score r = 0.45, p = 0.003) as well as between AOSD-specific biomarkers ferritin and IL-18. However, there was no significant difference in the serum CIRP levels among AOSD patients with three different disease phenotypes. CONCLUSIONS: These results suggest that CIRP may play a significant role in the pathophysiology of AOSD and could be a potential biomarker for monitoring the disease activity of AOSD.
33860677 Patients With Rheumatoid Arthritis With an Inadequate Response to Disease-Modifying Antirh 2021 Apr 20 Background Cardiovascular disease is the most common cause of death in patients with rheumatoid arthritis. It is believed that using disease-modifying antirheumatic drugs (DMARDs) to control inflammation can reduce the risk of cardiovascular disease. In this study, we investigated whether patients who responded differently to DMARDs might sustain different cardiovascular events. Methods and Results We designed a cohort study using the Chang Gung Research Database. We identified 7114 patients diagnosed with rheumatoid arthritis. After strict exclusion criteria, we collected 663 individuals as an inadequate response to DMARDs group. Then, 2034 individuals were included as the control group. The end point was composite vascular outcomes, including acute coronary syndrome or ischemic stroke. We used the inverse probability of treatment weighting to keep the covariates between these 2 groups well balanced. We compared the risk of these outcomes using the Cox proportional hazards model. The mean follow-up time was 4.7 years. During follow-up, there were 7.5% and 6.4% of patients with composite vascular outcomes in the DMARD-inadequate response and control groups, respectively. There was no significant difference in the risk of composite vascular outcomes (95% CI, 0.94-1.41) and ischemic stroke (95% CI, 0.84-1.36). The risk of acute coronary syndrome was significantly higher in the DMARD-inadequate response group (hazard ratio, 1.45; 95% CI, 1.02-2.05). Conclusions Patients with DMARD-inadequate response rheumatoid arthritis have a higher risk of developing acute coronary syndrome than those whose disease can be controlled by DMARDs.
34830460 Takinib Inhibits Inflammation in Human Rheumatoid Arthritis Synovial Fibroblasts by Target 2021 Nov 22 TGF β-activated kinase 1 (TAK1) is an important participant in inflammatory pathogenesis for diseases such as rheumatoid arthritis (RA) and gouty arthritis. The central position it occupies between the mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways makes it an attractive therapeutic target. As this field has developed in recent years, several novel inhibitors have been presented as having specific activity that reduces the TAK1 function either covalently as in the case of 5Z-7-oxozeanol (5Z7O) or reversibly (NG-25). However, the mechanism through which takinib elicits its anti-inflammatory activity remains elusive. While this inhibitor shows great promise, a thorough analysis of its inhibitor function and its potential off-target effects is necessary before addressing its clinical potential or its use in inflammatory conditions. An analysis through Western blot showed an unexpected increase in IL-1β-induced TAK1 phosphorylation-a prerequisite for and indicator of its functional potential-by takinib while simultaneously demonstrating the inhibition of the JAK/STAT pathway in human rheumatoid arthritis synovial fibroblasts (RASFs) in vitro. In THP-1 monocyte-derived macrophages, takinib again led to the lipopolysaccharide-induced phosphorylation of TAK1 without a marked inhibition of the TAK1 downstream effectors, namely, of c-Jun N-terminal kinase (JNK), phospho-c-Jun, NF-κB phospho-p65 or phospho-IκBα. Taken together, these findings indicate that takinib inhibits inflammation in these cells by targeting multiple signaling pathways, most notably the JAK/STAT pathway in human RASFs.