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ID PMID Title PublicationDate abstract
34274310 RETRACTED: Potential of ephedrine to suppress the gene expression of TNF-α, IL-1β, IL-6 2021 Oct 1 This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. A reader reported that Figure 9 of the above paper contains similar section with Figure 4 of another article authored by the same group in Inflammopharmacology, 29, (2021) 1119-1129, https://doi.org/10.1007/s10787-021-00840-9, and part of the Figure 9 of the above paper is used in Figure 9 of another article authored by the same group in Inflammopharmacology, 29, (2021) 673–682, https://doi.org/10.1007/s10787-021-00804-z. The journal requested the authors to explain the repeated use of the image and provide the raw data. However, the authors were not able to fulfill this request and therefore the Editor-in-Chief has decided to retract the article.
33244818 An interdigitated aptasensor to detect interleukin-6 for diagnosing rheumatoid arthritis i 2021 Dec Rheumatoid arthritis (RA) is an autoimmune disorder causing chronic inflammation in the small joints of the articular bone and destruction of articular cartilage. RA causes stiffness, pain, joint destruction, substantial comorbidity, and functional disability. Early-stage diagnosis of RA can help in the treatment of the disease and expand the patient life span. Interleukins are a group of inflammatory cytokines; in particular, an abundance of interleukin-6 (IL-6) was found in the synovial fluid and serum. In RA patients, the levels of IL-6 have been found to be correlated with the disease, and this work focused on detecting IL-6 by its aptamer with the help of a biotin-streptavidin strategy on an interdigitated electrode. A sensitivity of 1 fM (0.021 pg/mL) and a limit of detection of 10 fM (0.21 pg/mL) were found by a linear regression [y = 0.6413x - 0.6249; R² = 0.952] of the linear range from 1 fM to 100 pM. This method enhanced the immobilization of higher aptamer molecules for recognizing RA in serum-containing samples and is applicable to other diseases.
31789996 Contraceptive Use in Women of Childbearing Ability With Rheumatoid Arthritis. 2021 Apr 1 BACKGROUND/OBJECTIVE: Rheumatoid arthritis (RA) is a complex disease that may require treatment with one or several disease-modifying antirheumatic drugs (DMARDs). Many DMARDs have potential teratogenic effects or are newer agents with limited safety data in pregnancy. This study evaluated 20 common RA medications and the rate of contraceptive prescribing and counseling patterns in women with RA of childbearing ability. METHODS: This was an observational study of women with RA and childbearing ability aged 18 to 44 years who were seen at an academic rheumatology clinic from April 1, 2014, to March 31, 2016. Descriptive statistics and univariate logistic regression were used for analysis. RESULTS: One hundred fifty women were included in the analysis. The majority of patients were taking methotrexate (55.3%), followed by chronic prednisone (31.3%) and hydroxychloroquine (28.7%). A documented method of contraception was noted in 64/150 (42.7%). For women on contraception, most used combined oral contraceptives (31/64, 48.4%) or levonorgestrel intrauterine device (10/64, 15.6%). Of the 86 patients not on contraception, 19 (22.1%) received counseling regarding a pregnancy plan. CONCLUSIONS: Most women with RA of childbearing age and ability were not using contraception. Among these patients, only a minority prescribed DMARD therapy had documented pregnancy or contraceptive counseling. Women with RA who were prescribed with a DMARD should discuss the use of effective contraception with their provider if sexually active and not desiring pregnancy or wanting to avoid potential teratogenic effects. Potential strategies are discussed to improve healthcare delivery to this population in hopes of avoiding unintended pregnancy and potential teratogenic effects of RA medications.
32951253 The value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as comple 2021 Jan BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have drawn attention in recent years as novel non-specific inflammatory markers; however, only a few studies have been conducted to investigate their value in RA. OBJECTIVE: To investigate the value of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as complementary diagnostic tools in rheumatoid arthritis (RA). METHOD: This study included 1009 patients with RA, 170 patients with other rheumatic diseases, and 245 healthy individuals from four medical centers. The patients' general data, including complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF), were retrospectively analyzed, and the NLR and PLR were calculated. Potential effective indicators were screened by logistic regression analysis, and a receiver operating characteristic (ROC) curve was plotted to evaluate their diagnostic value for RA. RESULTS: (a) The NLR and PLR were significantly higher in the RA group than in the non-RA group and the control group (P < .05). (b) Spearman's Rho showed that the NLR was positively correlated with the PLR (r = .584, P < .05), RF (r = .167, P < .01), and CRP (r = .280, P < .01) but was not significantly correlated with ESR (r = .100, P > .05). The PLR was positively correlated with RF (r = .139, P < .01), CRP (r = .297, P < .01), and ESR (r = .262, P < .05). (c) Logistic analysis showed that RF, CRP, ESR, and the NLR had diagnostic value for RA. (d) For the NLR, the area under the curve (AUC) of the ROC curve was 0.831; at the cutoff value of 2.13, the diagnostic sensitivity, specificity, accuracy, and Youden index were 76.7%, 75.9%, 76.4%, and 0.5424, respectively. CONCLUSION: The NLR was less effective than CRP and RF but was superior to ESR in the diagnosis of RA. The NLR can thus be used as a complementary diagnostic indicator in the diagnosis of RA.
34420399 Rheumatoid arthritis activity scores in patients with and without fibromyalgia syndrome. 2021 Jul BACKGROUND: Fibromyalgia syndrome (FM) is a systemic disease of unknown etiology, which can cause widespread musculoskeletal pain. In patients with rheumatoid arthritis (RA), FM can cause an additional symptom burden, which can affect some variables on the RA disease activity score 28 (DAS28), a tool that evaluates 28 joints in RA patients. OBJECTIVE: Compare the results of four different versions of the DAS28 and the parameters used to determine disease activity scores in RA patients with and without FM, and determine whether there are treatment differences between RA patients with and without FM. DESIGN: Retrospective, cross-sectional. SETTING: Tertiary hospital. PATIENTS AND METHODS: We identified patients diagnosed with RA between 1 September 2016 and 1 February 2020 and identified patients with and without FM. MAIN OUTCOME MEASURES: Differences between variables in the DAS28 calculations (tender joint count [TJC], patient global assessment [PGA], and others), between patients with and without FM, and differences between patients with and without FM who were using or not using biological agents. SAMPLE SIZE: 381, including 322 females (84.5%). RESULTS: The frequency of FM in RA patients was 25.7% (89 females, 24.6%). In RA patients with FM, the TJC and PGA median values were significantly higher than in patients without FM (P<.05). The use of corticosteroids and biological therapy in patients with FM was more frequent than in patients without FM (P<.05). Compared to patients without FM, patients with FM switched treatment more often because of non-response to treatment (P=.01) Median values of the DAS28 scores (calculated by four different versions of the instrument) in RA patients with FM were higher than in patients without FM (P<.05). CONCLUSION: The presence of FM in RA patients may affect the subjective variables in different versions of DAS28 scores, causing the disease activity to score higher on the instrument, erroneously indicating worse disease than is actually present. LIMITATIONS: A single center, retrospective study. CONFLICTS OF INTEREST: None.
34226432 Impact of the mandatory confinement during the first wave of the SARS-CoV-2/COVID-19 pande 2021 Apr OBJECTIVE: The aim of this study was to evaluate the self-reported impact of mandatory confinement occurring in the first wave of the SARS-CoV-2 pandemic in Portuguese patients with rheumatoid arthritis (RA), as a means to improve care during this and in future pandemics. MATERIAL AND METHODS: The web-based survey COVIDRA was developed to assess 5 domains including RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. RESULTS: We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%) with a mean age of 58 years. The majority had disease lasting >10 years and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23.7%). Over 40% experienced symptom worsening during confinement, almost half considered moderate or severe. Mobility restriction and increased stress, anxiety or depression were responsible for this worsening. Only 2.5% reduced or withheld their immunosuppressive medication due to fear of becoming infected with SARS-CoV-2. After confinement, 16.2% of those previously employed were in a lay-off regime and 3% lost their jobs. Most employed RA patients practiced telework during confinement. The majority of patients decreased or did not practice any physical exercise (80.5%). Symptoms of anxiety and depression developed or worsened in 67.3% and 51.9% respectively, approximately one third were considered moderate or severe. CONCLUSIONS: Portuguese RA patients experienced significant symptom worsening, anxiety and depression during the first wave confinement. Only a minority changed their immunosuppressive treatment for fear of SARS-CoV-2 infection. Published literature on these matters shows results very similar to ours.
34403518 Influences of the lncRNA TUG1-miRNA-34a-5p network on fibroblast-like synoviocytes (FLSs) 2021 Sep BACKGROUND: Rheumatoid arthritis (RA) is a systemic and chronic inflammatory disease. The cellular glucose metabolism of fibroblast-like synoviocytes (FLSs) of RA has been revealed to be essential to the pathogenesis and development of RA. To date, the precise roles and molecular mechanisms of long noncoding RNA TUG1 in RA have not been elucidated. METHODS: TUG1 and miR-34a-5p were detected by qRT-PCR. Interactions between lncRNA-miRNA and miRNA-mRNA were validated by RNA pull-down assay and luciferase assay. The glucose metabolism was evaluated by glucose uptake and extracellular acidification rate (ECAR). Cell viability was determined by MTT assay and Annexin V assay. RESULTS: TUG1 expression was significantly upregulated in synovial fibroblast-like synoviocytes (FLSs) compared with normal FLSs. Functional assays uncovered that silence of TUG1 suppressed FLSs-RA invasion, migration, glucose metabolism, and increased apoptosis. Bioinformatics analysis indicated that TUG1 interacted with miR-34a-5p. RNA pull-down assay and luciferase assay validated that TUG1 sponged miR-34a-5p in FLSs-RA. Overexpression of miR-34a-5p effectively inhibited glucose metabolism of FLSs-RA. Furthermore, the glucose metabolism of FLSs-RA was significantly elevated compared with normal FLSs. The glucose metabolism enzyme, LDHA, was directly targeted by miR-34a-5p in FLSs. Rescue experiments validated that the miR-34a-5p-inhibited glucose metabolism of FLSs-RA was through targeting LDHA. Finally, we showed restoration of miR-34a-5p in TUG1-overexpressing FLSs-RA successfully overcame the TUG1-promoted glucose metabolism and apoptosis resistance via targeting LDHA. CONCLUSION: The present study uncovered critical roles and molecular mechanisms underlying the TUG1-mediated glucose metabolism and apoptosis of FLSs-RA through modulating the miR-34a-5p-LDHA pathway in fibroblast-like synoviocytes of rheumatoid arthritis.
33389220 Plasma miRNAs improve the prediction of coronary atherosclerosis in patients with rheumato 2021 Jun OBJECTIVE: MicroRNAs (miRNAs) regulate gene expression and are disease biomarkers. Rheumatoid arthritis (RA) patients have accelerated atherosclerosis leading to excess cardiovascular morbidity and mortality, but traditional risk factors for cardiovascular risk stratification are inadequate. In the general population, miRNAs improve cardiovascular risk estimation beyond traditional risk factors. Our objective was to develop a miRNA panel that predicts coronary atherosclerosis in RA patients. METHODS: Plasma small RNA next-generation sequencing (NGS) was performed on 161 RA patients whose Agatston scores for coronary artery calcium were previously measured. Random forest analysis of plasma NGS miRNA expression was used to determine which miRNAs best differentiated between those patients with and without coronary artery calcium. Top predictive miRNAs were assayed by quantitative PCR (qPCR). Elastic net regression was used to develop the most parsimonious models with qPCR-measured miRNA concentrations and clinical variables (age, sex, ACC/AHA 10-year risk score, DAS28 score, and diabetes) separately to predict the presence of coronary artery calcium and high coronary artery calcium. C-statistics were used to assess performance model performance. RESULTS: The top miRNAs which differentiated those with and without coronary atherosclerosis based on random forest analysis included let-7c-5p, miR-30e-5p, miR-30c-5p, miR-4446-3p, miR-126-5p, miR-3168, miR-425-5p, miR-126-3p, miR-30a-5p, and miR-125a-5p. For coronary artery calcium prediction, addition of all miRNAs except miR-126-3p to clinical factors improved the c-statistic modestly from 0.86 to 0.87. For high coronary artery calcium prediction, addition of all miRNAs except miR-30c-5p to clinical factors improved the c-statistic from 0.75 to 0.80. CONCLUSION: A plasma miRNA panel improved the prediction of high coronary artery calcium beyond traditional risk factors and RA disease activity. Further evaluation of the miRNA panel for prediction of coronary events in RA is necessary. Key Point • A plasma microRNA panel including let-7c-5p, miR-30a-5p, miR-30e-5p, miR-125a-5p, miR-126-3p, miR-126-5p, miR-425-5p, miR-3168, and miR-4446-3p improved the prediction of high coronary artery calcium beyond clinical factors in patients with rheumatoid arthritis.
33504577 Effect of significant weight loss on disease activity: reason to implement this non-pharma 2021 Jan Obesity is very common in patients with inflammatory rheumatic diseases (IRDs), of which between 27% and 37% of patients have a body mass index ≥30 kg/m(2) In addition to further increasing the risk of developing cardiovascular diseases (CVDs) in this group of patients, obesity is associated with higher disease activity and a lower response to drug therapy. This case series showed that in those patients with rheumatoid arthritis or psoriatic arthritis with a substantial weight loss of >10% of body mass, median Disease Activity Score 28 joints score decreased with 0.9. This reduction in disease activity resulted in an increase in the percentage of patients achieving remission from 6% to 63%. This reduction in disease activity was obtained without intensification of medical treatment in 87% of the patients. This case series supports the current evidence that weight reduction has positive effects on the course of the disease and thus also on the CVD risk profile in these patients. Therefore, weight loss can serve as a non-pharmacological treatment option in obese patients with IRDs.
34790203 Role of microRNA Shuttled in Small Extracellular Vesicles Derived From Mesenchymal Stem/St 2021 Osteoarticular diseases (OD), such as rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic autoimmune/inflammatory and age-related diseases that affect the joints and other organs for which the current therapies are not effective. Cell therapy using mesenchymal stem/stromal cells (MSCs) is an alternative treatment due to their immunomodulatory and tissue differentiation capacity. Several experimental studies in numerous diseases have demonstrated the MSCs' therapeutic effects. However, MSCs have shown heterogeneity, instability of stemness and differentiation capacities, limited homing ability, and various adverse responses such as abnormal differentiation and tumor formation. Recently, acellular therapy based on MSC secreted factors has raised the attention of several studies. It has been shown that molecules embedded in extracellular vesicles (EVs) derived from MSCs, particularly those from the small fraction enriched in exosomes (sEVs), effectively mimic their impact in target cells. The biological effects of sEVs critically depend on their cargo, where sEVs-embedded microRNAs (miRNAs) are particularly relevant due to their crucial role in gene expression regulation. Therefore, in this review, we will focus on the effect of sEVs derived from MSCs and their miRNA cargo on target cells associated with the pathology of RA and OA and their potential therapeutic impact.
34247731 Directional self-assembly of anisotropic bimetal-poly(aniline) nanostructures for rheumato 2021 Aug 22 Anisotropic organic-inorganic hybrid nanoparticles possessing different functionalities and physicochemical properties from each compartment have attracted significant interest for the development of advanced functional materials. Moreover, their self-assembled structures exhibit unique optical properties for photonics-based biosensing. We report herein the fabrication of anisotropic bimetal-polymer nanoparticles (ABPNs) via combination of oxidative polymerization and additional growth of metallic nanoparticles on Au seeds as well as their directional clustering mediated via noncovalent interactions. Polymerization of anilines for poly (aniline) shell was conducted by reducing silver nitrate onto the Au seed in the presence of a surfactant, giving rise to spatially distinct bimetallic Au core and Ag shell compartment and the poly (aniline) counter-one that comprise the ABPNs. Furthermore, ABPNs were directionally clustered in a controlled manner via hydrophobic interaction, when the bimetallic compartment was selectively modified. These nanoclusters showed highly enhanced optical properties owing to the increased electromagnetic fields while the poly (aniline) being used to offer antibody binding capacity. Taking advantages of those properties of the ABPN nanoclusters, surface-enhanced Raman scattering (SERS) intensity-based quantification of two different biomarkers: autoantibodies against cyclic citrullinated peptide and rheumatoid factor was demonstrated using ABPN nanoclusters as SERS nanoprobes. Conclusively, this work has great potential to satisfy a need for multiplexing in diagnosis of early stage of rheumatoid arthritis.
32662413 ICHIBAN, a non-interventional study evaluating tocilizumab long-term effectiveness and saf 2021 Mar OBJECTIVES: We aimed to measure long-term effectiveness and safety of tocilizumab in patients with rheumatoid arthritis in daily German practice. METHODS: ICHIBAN was a prospective, multi-centre, non-interventional study (ML22928) that enrolled adult patients with active moderate to severe rheumatoid arthritis. Patients were to be treated according to tocilizumab label and observed for up to two years. Effectiveness outcomes included DAS28-ESR remission, EULAR response, CDAI and HAQ. RESULTS: Overall, 3164 patients received at least one dose of tocilizumab. Patient mean age was 55.5±13.1 years (74.8% female). At baseline, 72.1% of patients had at least one comorbidity. Approximately 50.9% of patients received concomitant csDMARDs, mostly methotrexate, and 80.7% received concomitant glucocorticoids (GCs). In patients receiving GCs at baseline, the mean dose decreased from 9.32±16.36 mg/d to 4.60±4.48 mg/d at week 104. In the effectiveness population with no prior TCZ (n=2902), 61.4% of patients achieved the primary outcome, DAS28-ESR remission. Improvements were seen as early as week 4. At week 104, 77.9% of patients had DAS28-ESR low disease activity, 89.6% achieved good or moderate EULAR response, and 29.5% achieved a CDAI-based remission. Effectiveness outcomes were similar in all previous therapy subgroups. The incidence of serious infections was similar to the rates in former studies involving tocilizumab. Patients receiving GC at baseline experienced slightly higher rates of treatment-related serious adverse events, mainly infections. No new safety signals were observed. CONCLUSIONS: Long-term effectiveness and safety in ICHIBAN were in line with previously reported tocilizumab efficacy and safety studies.
34773692 Investigation of the correlation between mood disorder symptoms and disease activity and f 2021 Dec 13 BACKGROUND/AIM: To investigate the correlation between depressive-anxiety symptoms, mixed features, disease activity, and functional status in patients with rheumatoid arthritis (RA) in the light of the shared underlying etiology in both disorders. MATERIALS AND METHODS: The study included 556 patients with RA. RA disease activity was measured using the Disease Activity Score 28-joint count C reactive protein (DAS28-CRP), and the patients were evaluated by a Health Assessment Questionnaire (HAQ). The Hospital Anxiety and Depression Scale (HADS), Mood Disorder Questionnaire (MDQ), and Modified Hypomania Checklist (mHCL) were used to evaluate the mixed depression and bipolarity status of the patients. RESULTS: Of the patients, 430 (77.3%) were female and 126 (22.7%) were male. The median age was 57 years, the median HAQ score was 0.55 points, and the median DAS28-CRP score was 4.1 points. The evaluation of the patients by DAS28-CRP revealed that 58.5% of the patients had moderate and severe disease activity, while only 23.4% of them were in remission. The group using the combination of synthetic disease-modifying anti-rheumatic drugs (sDMARD) and steroid therapy had significantly higher HAD-depression, HAD-anxiety, mHCL, DAS28-CRP, HAQ, and MDQ scores than the group using sDMARD alone. The grouping of the patients based on the DAS28-CRP cut-off scores showed that the patients with moderate and severe disease activity had significantly higher HADS, mHCL, MDQ scores than those in remission and those with mild disease activity (p < 0.001). CONCLUSION: Disease severity and functional status in RA can be affected by comorbid anxiety-depressive and mixed symptoms. Therefore, clinicians should consider screening the depressive-anxiety and mixed mood symptoms of RA patients. Moreover, patients who use steroid therapy are more susceptible to mood symptoms (anxiety, depression, bipolarity), which should also be considered during the follow-up of patients.
34706771 Treatment response and several patient-reported outcomes are early determinants of future 2021 Oct 27 BACKGROUND: Self-efficacy, or patients' confidence in their ability to control disease and its consequences, was recently prioritised in EULAR recommendations for inflammatory arthritis self-management strategies. However, it remains unclear which factors influence self-efficacy in early rheumatoid arthritis (RA). METHODS: Data were analysed from the 2-year RCT Care in early RA (CareRA), which studied remission-induction treatment regimens for early RA. Participants completed the Arthritis Self-Efficacy Scale (ASES), Short-Form 36 (SF-36), Revised Illness Perception Questionnaire (IPQ-R), Utrecht Coping List (UCL), RAQoL and Health Assessment Questionnaire (HAQ). Depending on time to first remission (DAS28-CRP < 2.6) and persistence of remission, treatment response was defined as persistent response, secondary failure, delayed response, late response or non-response. The association between ASES scores and clinical/psychosocial factors was explored with Spearman correlation and multivariate linear mixed models. Baseline predictors of week 104 ASES were identified with exploratory linear regression followed by multiple regression of significant predictors adjusted for DAS28-CRP, HAQ, treatment arm, treatment response, cumulative CRP/SJC28 and demographic/serologic confounders. RESULTS: All 379 patients had a recent diagnosis of RA and were DMARD-naïve at study initiation. Most patients were women (69%) and RF/ACPA-positive (66%), and the mean (SD) age was 52 (13) years. For all tested outcome measures, better perceived health correlated with higher self-efficacy. While patient-reported factors (HAQ, SF-36, RAQoL, IPQ-R, pain, fatigue and patient's global assessment) showed moderate/strong correlations with ASES scores, correlations with physician-reported factors (physician's global assessment, SJC28), TJC28 and DAS28-CRP were weak. Only more favourable outcomes on patient-reported factors and DAS28-CRP were associated with higher ASES scores at each time point. An earlier, persistent treatment response predicted higher ASES scores at both weeks 52 and 104. Significant baseline predictors of week 104 ASES included HAQ; SF-36 mental component score, vitality, mental health and role emotional; IPQ-R illness coherence, treatment control, emotional representations and consequences; UCL Passive reacting; and the RAQoL. CONCLUSIONS: Patient-reported outcomes and treatment response were early determinants of long-term self-efficacy in an early RA trial. These results provide further relevance for the window of opportunity in an early treat-to-target strategy and could help to timely identify patients who might benefit from self-management interventions. TRIAL REGISTRATION: EudraCT 2008-007225-39.
33846189 Does withdrawal of immunosuppression in rheumatoid arthritis after SARS-CoV-2 infection in 2021 Apr 12 We describe a case of a 48-year-old woman who presented with acute respiratory failure due to diffuse alveolar haemorrhage and acute renal failure due to pauci-immune glomerulonephritis consistent with a new diagnosis of microscopic polyangiitis (MPA). The patient had a recent SARS-CoV-2 infection 6 weeks before MPA diagnosis and had stopped immunosuppression for her rheumatoid arthritis (RA) at that time. The patient was treated with pulse intravenous steroids, plasma exchange therapy and rituximab, which induced remission of her illness. This case highlights a timely dilemma of holding immunosuppression in a RA patient with low disease activity on combination therapy with SARS-CoV-2 infection, and the potential risk of developing an additional autoimmune disease, such as vasculitis, given their existing autoimmunity due to RA.
34691030 Identification of Diagnostic Signatures and Immune Cell Infiltration Characteristics in Rh 2021 BACKGROUND: Rheumatoid arthritis (RA) refers to an autoimmune rheumatic disease that imposes a huge burden on patients and society. Early RA diagnosis is critical to preventing disease progression and selecting optimal therapeutic strategies more effectively. In the present study, the aim was at examining RA's diagnostic signatures and the effect of immune cell infiltration in this pathology. METHODS: Gene Expression Omnibus (GEO) database provided three datasets of gene expressions. Firstly, this study adopted R software for identifying differentially expressed genes (DEGs) and conducting functional correlation analyses. Subsequently, we integrated bioinformatic analysis and machine-learning strategies for screening and determining RA's diagnostic signatures and further verify by qRT-PCR. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. Moreover, this study employed cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) website for assessing the inflammatory state of RA, and an investigation was conducted on the relationship of diagnostic signatures and infiltrating immune cells. RESULTS: On the whole, 54 robust DEGs received the recognition. Lymphocyte-specific protein 1 (LSP1), Granulysin (GNLY), and Mesenchymal homobox 2 (MEOX2) (AUC = 0.955) were regarded as RA's diagnostic markers and showed their statistically significant difference by qRT-PCR. As indicated from the immune cell infiltration analysis, resting NK cells, neutrophils, activated NK cells, T cells CD8, memory B cells, and M0 macrophages may be involved in the development of RA. Additionally, all diagnostic signatures might be different degrees of correlation with immune cells. CONCLUSIONS: In conclusion, LSP1, GNLY, and MEOX2 are likely to be available in terms of diagnosing and treating RA, and the infiltration of immune cells mentioned above may critically impact RA development and occurrence.
33968050 Novel Insights Into Rheumatoid Arthritis Through Characterization of Concordant Changes in 2021 In this study, we sought to characterize synovial tissue obtained from individuals with arthralgia and disease-specific auto-antibodies and patients with established rheumatoid arthritis (RA), by applying an integrative multi-omics approach where we investigated differences at the level of DNA methylation and gene expression in relation to disease pathogenesis. We performed concurrent whole-genome bisulphite sequencing and RNA-Sequencing on synovial tissue obtained from the knee and ankle from 4 auto-antibody positive arthralgia patients and thirteen RA patients. Through multi-omics factor analysis we observed that the latent factor explaining the variance in gene expression and DNA methylation was associated with Swollen Joint Count 66 (SJC66), with patients with SJC66 of 9 or more displaying separation from the rest. Interrogating these observed differences revealed activation of the immune response as well as dysregulation of cell adhesion pathways at the level of both DNA methylation and gene expression. We observed differences for 59 genes in particular at the level of both transcript expression and DNA methylation. Our results highlight the utility of genome-wide multi-omics profiling of synovial samples for improved understanding of changes associated with disease spread in arthralgia and RA patients, and point to novel candidate targets for the treatment of the disease.
33377396 Differential synovial tissue expression of TLRs in seropositive and seronegative rheumatoi 2021 Feb Toll-like receptors (TLRs) are known to have an important role in triggering the innate immune response and in priming antigen-specific adaptive immunity and inflammation. The differences in synovial tissue expression of the TLRs between seronegative and seropositive rheumatoid arthritis (RA) were examined from 9 seropositive RA, 5 seronegative RA and 4 osteoarthritis (OA) patients. Synovitis status was assessed using Krenn's scoring and TLR 1-9 expression by immunohistochemistry. Tissue citrulline content was analysed by HPLC method. In RA TLR expression was generally higher than in OA. TLR2 expression was higher in both seronegative and seropositive RA compared to OA. TLR 1, 4 and 8 expressions were higher in seropositive RA than in seronegative RA or in OA. For TLRs 3, 5, 6, 7 and 9 local differences of expression were found between groups. TLR 1-9 expression correlated with the synovitis grade. No statistical difference was found in synovial tissue citrulline content between the groups. In seropositive RA, the TLR repertoire in the synovial tissue differs from seronegative RA and could explain differences in disease outcomes. The high expression of protein sensing (TLR1, TLR2 and TLR4) and nucleic acid sensing TLRs (TLR7, TLR8 and TLR9) in the seropositive RA could make the synovium primed for reacting to citrullinated proteins and nucleic acids that could be released to extracellular space in formation of neutrophil extracellular traps. This reactivity could be augmented by Fc receptor activation by anti-citrullinated protein antibody immunocomplexes associated with seropositive RA.
35261017 Sleep disturbances in chronic rheumatic diseases: Is disease activity the major determinan 2021 Aout INTRODUCTION: Sleep disturbances are closely related to chronic pain processes, especially in patients with inflammatory and mechanical joint diseases. OBJECTIVES: This study aims to report sleep characteristics in patients with rheumatoid arthritis (RA) and knee osteoarthritis also to determine the responsibility of disease activity in the occurrence of sleep disturbances during chronic rheumatic diseases. METHODS: We conducted a comparative study between two groups of patients: the first with RA, the second with primary knee osteoarthritis. We reported sociodemographic and medical data (clinical and biological inflammatory syndrome data). Then, we assessed depression, anxiety, and sleep disturbances with respectively Beck Depression Inventory, Beck Anxiety Inventory and Medical Outcome Study Sleep Scale (MOS-SS). RESULTS: Seventy RA patients aged 51.9 years, with an average of 77.1% female were studied. The mean disease duration was 6.9 years. All sleep domains were altered in these patients. Forty patients with knee osteoarthritis aged 57.5 years with an average of 70% female were included. The mean disease duration was 4 years. The most impaired domains in this group were somnolence and sleep disturbance. Multivariate analysis concluded that risk factors independently related to RA were:  disease activity score, functional disability, depression, anxiety, and body mass index. Disease activity score were the only parameter to influence all domains of sleep. CONCLUSION: So we result that disease activity is a risk factor independently related to sleep disturbances in rheumatoid arthritis. Furthermore, mood disorders and obesity also deteriorate several sleep domains. These factors must be considered in the management of chronic rheumatic disorders.
34074293 Association between serum bone biomarker levels and therapeutic response to abatacept in p 2021 Jun 1 BACKGROUND: To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. METHODS: We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients' clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. 'Power Doppler (PD) responder' was defined as a patient whose Δtotal PD score over 6 months was greater than the median change. RESULTS: Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23-0.91, p = 0.043) was an independent predictor of PD responder status. CONCLUSION: Serum levels of bone biomarkers may be useful for predicting RA patients' therapeutic responses to abatacept. TRIAL REGISTRATION: Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study Trial registration number: UMIN000012524 Date of registration: 12/9/2013 URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657.