Browse

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

ID PMID Title PublicationDate abstract
35356000 The Programmed Death-1 Pathway Counter-Regulates Inflammation-Induced Osteoclast Activity 2022 OBJECTIVE: The programmed death-1 (PD-1) pathway is essential for maintaining self-tolerance and plays an important role in autoimmunity, including rheumatoid arthritis (RA). Here, we investigated how membrane-bound and soluble (s)PD-1 influence bone homeostasis during chronic inflammation, exemplified in RA. METHODS: Bone mineral density and bone microstructure were examined in PD-1 and PD-L1 knockout (KO) mice and compared with wild-type (WT) mice. Receptor activator of nuclear factor kappa-B ligand (RANKL) was measured in serum, and the expression examined on activated bone marrow cells. Osteoclast formation was examined in cells from murine spleen and bone marrow and from human synovial fluid cells. sPD-1 was measured in chronic and early (e)RA patients and correlated to markers of disease activity and radiographic scores. RESULTS: PD-1 and PD-L1 KO mice showed signs of osteoporosis. This was supported by a significantly reduced trabecular bone volume fraction and deteriorated microstructure, as well as increased osteoclast formation and an increased RANKL/OPG ratio. The recombinant form of sPD-1 decreased osteoclast formation in vitro, but was closely associated with disease activity markers in eRA patients. Sustained elevated sPD-1 levels indicated ongoing inflammation and were associated with increased radiographic progression. CONCLUSION: The PD-1 pathway is closely associated with bone homeostasis, and lacking members of this pathway causes a deteriorated bone structure. The immunological balance in the microenvironment determines how the PD-1 pathway regulates osteoclast formation. In eRA patients, sPD-1 may serve as a biomarker, reflecting residual but clinically silent disease activity and radiographic progression.
34837762 Sesquiterpenes from Kadsura coccinea attenuate rheumatoid arthritis-related inflammation b 2022 Feb The roots of Kadsura coccinea is commonly used in Tujia ethnomedicine, named "heilaohu", having the effect of treating rheumatic arthritis (RA). Chemical investigation on the ethanol extract of heilaohu led to the isolation of one undescribed cuparane sesquiterpenoid, heilaohusesquiterpenoid A, one undescribed carotane sesquiterpenoids, heilaohusesquiterpenoid B, and eighteen sesquiterpene derivatives. Their structures were subsequently determined based on their 1D and 2D-NMR, HR-ESI-MS, and ECD spectroscopic data. Gaultheriadiolide was the most cytotoxic compound against the proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells with an IC(50) value of 9.37 μM. In the same line, nine compounds exhibited significant inhibition effects against TNF-α and IL-6 release in the LPS-induced RAW264.7 cells with IC(50) values ranging between 1.03 and 10.99 μM. The potential molecular mechanisms of the active compounds against RA were established through pharmacological network analysis based on the initial screening results. Experimental validation showed that gaultheriadiolide suppressed inflammation by inhibiting the NF-kB and JAK2/STAT3 pathways. This study enriches the structural diversity of sesquiterpenes in K. coccinea and lays a foundation for further anti-RA and anti-inflammatory studies.
35447521 Combined 16S rRNA gene sequencing and metabolomics to investigate the protective effects o 2022 May 30 Wu-tou decoction (WTD) is a traditional Chinese medicine (TCM) formula which has been used for treating rheumatoid arthritis (RA) for a thousand years. However, the underlying mechanism of WTD in treating RA is still unclear. In recent years, more and more attention has been paid to the role of gut microbiota and microbiota-derived metabolites in the treatment of RA. Hence, this study aims to investigate the roles of microbiota and microbial metabolites in the treatment of RA with WTD. Firstly, the therapeutic effects of WTD on adjuvant-induced arthritis (AIA) rats were evaluated. Then, the 16S rRNA sequencing analysis was used to clarify the changes of the intestinal microbiota and obtain the key microbiota affected by WTD. The important microbial metabolites were quantitated to explore the metabolic characteristics of WTD against RA by targeted metabolomics method. Finally, correlation analysis was performed to investigate the functional correlation among the gut microbiota, metabolites and RA-related serum indexes. The results indicated that WTD could relieve arthritis and reverse gut microbiota dysbiosis. The variation of short-chain fatty acids, bile acids, tryptophan metabolites and amino acids, which are important microbial metabolites, were reversed by WTD intervention. The correlation studies proved that WTD could regulate inflammation and intestinal barrier function partially by modulating Bacteroides, Prevotella, Akkermansia and their associated acetic acid, butyric acid, cholic acid and indole propionic acid. The anti-RA effects of WTD were partially mediated by gut microbiota and microbial metabolites. This study provides a new insight for treating RA and highlights the importance of gut microbiota in the treatment of diseases.
35235611 Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis 2022 BACKGROUND: Porana sinensis Hemsl. has been widely used as a substitute for Erycibes Caulis to treat rheumatoid arthritis (RA) in traditional Chinese medicine (TCM). However, little is known about the active ingredients and pharmacological mechanisms that mediate the action of P. sinensis against RA. METHODS: The compounds contained in P. sinensis were analyzed by Q Exactive Focus mass spectrometer. The active constituents and pharmacological mechanism of P. sinensis against RA were clarified using a network pharmacology-based investigation. LPS-induced RAW 264.7 cells was used to verify anti-inflammatory effects of the active compounds screened by network pharmacology. Collagen-induced arthritis model was used to further investigate the mechanism of P. sinensis against RA. RESULTS: The potential components and targets of P. sinensis against RA were analyzed using network pharmacology, and five compounds, twenty-five targets, and eight pathways were identified. Experimental validation suggested that P. sinensis extract and five compounds (esculetin, umbelliferone, trans-N-feruloyltyramine, caffeic acid and scopolin) could inhibit the release of inflammatory mediators (NO, TNF-α, IL-1β and IL-6) in LPS-induced RAW 264.7 cell. P. sinensis extract attenuated the severity, pathological changes, and release of cytokines (IL-6 and HIF-1α) during RA progression by regulating the PI3K/AKT and HIF-1 pathways. CONCLUSION: The study provides a basis for the application of P. sinensis against RA. Our findings may provide suggestions for developing P. sinensis into a substitute for Erycibes Caulis.
35030388 Perillyl alcohol attenuates rheumatoid arthritis via regulating TLR4/NF-κB and Keap1/Nrf2 2022 Mar BACKGROUND: Rheumatoid arthritis is a chronic and idiopathic autoimmune disorder. Perillyl alcohol (POH) is a monoterpene which can be extracted from widely available essential oils and is known for its strong anti-inflammatory and anti-oxidant properties. HYPOTHESIS/PURPOSE: Recent studies have been proven that inhibitors of farnesyltransferase enzyme showed significant anti-arthritic activity. POH is one such natural molecule having anti-inflammatory and anti-oxidant properties by inhibiting farnesyltransferase enzyme which further down regulates NF-κB and Nrf2 via Ras/Raf/MAPK pathway. Also, the effect of POH against rheumatoid arthritis is not known yet. Hence, the present research was intended to assess the anti-arthritic potential of POH in-vitro and in-vivo. METHODS: The in-vitro effects of POH on RAW 264.7 cells stimulated with LPS 1 µg/ml were investigated to its potential therapeutic effects. CFA 100 µl was intradermally administered to rats for the induction of arthritis. POH 100 mg/kg and 200 mg/kg administered topically from day 1 to day 28. Paw volumes measured, radiography analysis, anti-oxidant status, Gene expression studies, western blot analysis and histological analysis were performed to check the effects of POH. RESULTS: Our in-vitro findings suggested that POH inhibits inflammation by suppressing reactive oxygen species (ROS), NF-кB and Nrf2 signaling axis. Besides this, POH also rescinded the nitrate levels, pro-inflammatory cytokine levels like IL-1β, IL-6 and TNF-α also PGE2 and COX-2 levels induced by LPS in murine macrophages. Additionally, our in-vivo results revealed that POH conscientiously alleviated CFA induced inflammation by restoring arthritis index, body weight, nitrosative, lipid peroxidation assays. Macroscopically through measuring paw volumes and X-ray, it was evidenced that POH has decreased inflammation and bone erosion. Not only in-vitro but also in-vivo, POH has abridged cytokine levels IL-1β, IL-6, and TNF-α. Histopathological evaluation presented POH treatment alleviated joint inflammation, pannus formation, and bone erosion significantly. Moreover, POH suppressed the protein expression of NF-кB, COX-2, iNOS and improved Nrf2, and SOD2 levels in paw tissues estimated by western blotting. CONCLUSION: POH was effective in ameliorating LPS stimulation mediated oxidative stress and pro-inflammatory cytokines in RAW 264.7 cells in-vitro and FCA induced arthritis in rats in-vivo through its anti-inflammatory effects via regulating TLR4/NF-κB and Keap1/Nrf2 signaling pathways..
34492323 Fengshi Qutong capsule ameliorates bone destruction of experimental rheumatoid arthritis b 2022 Jan 10 ETHNOPHARMACOLOGICAL RELEVANCE: Bone destruction plays a key role in damaging the joint function of rheumatoid arthritis (RA). Fengshi Qutong capsule (FSQTC) consisting of 19 traditional Chinese medicines has been used for treating RA in China for many years. Preliminary studies show that FSQTC has analgesic activity and inhibits synovial angiogenesis of collagen-induced arthritis (CIA), but its role on bone destruction of RA is still unclear. AIM OF THE STUDY: To explore the effect of FSQTC on bone destruction of RA and the possible mechanism of osteoclastogenesis in vivo and in vitro. MATERIALS AND METHODS: LC-MS system was used to detect the quality control components of FSQTC. The anti-arthritic effect of FSQTC on CIA rats was evaluated by arthritis score, arthritis incidence and histopathology evaluation of inflamed joints. The effect of treatment with FSQTC on bone destruction of joint tissues was determined with X-ray and micro-CT quantification, and on bone resorption marker CTX-I and formation marker osteocalcin in sera were detected by ELISA. Then, osteoclast differentiation and mature were evaluated by TRAP staining, actin ring immunofluorescence and bone resorption assay both in joints and RANKL-induced RAW264.7 cells. In addition, RANKL, OPG, IL-1β and TNFα in sera were evaluated by ELISA. The molecular mechanisms of the inhibitions were elucidated by analyzing the protein and gene expression of osteoclastic markers CTSK, MMP-9 and β3-Integrin, transcriptional factors c-Fos and NFATc1, as well as phosphorylation of ERK1/2, JNK and P38 in joints and in RANKL-induced RAW264.7 cells using western blot and/or qPCR. RESULTS: In this study, 12 major quality control components were identified. Our data showed that FSQTC significantly increased bone mineral density, volume fraction, trabecular thickness, and decreased trabecular separation of inflamed joints both at periarticular and extra-articular locations in CIA rats. FSQTC also diminished the level of CTX-I and simultaneously increased osteocalcin in sera of CIA rats. The effects were accompanied by reductions of osteoclast differentiation, bone resorption, and expression of osteoclastic markers (CTSK, MMP-9 and β3-Integrin) in joints. Interestingly, FSQTC treatment could reduce the protein level of RANKL, increase the expression of OPG, and decrease the ratio of RANKL to OPG in inflamed joints and sera of CIA rats. In addition, FSQTC inhibited the levels of pro-inflammatory cytokines implicated in bone resorption, such as IL-1β and TNFα in sera. When RAW264.7 cells were treated with RANKL, FSQTC inhibited the formation of TRAP + multinucleated cells, actin ring and the bone-resorbing activity in dose-dependent manners. Furthermore, FSQTC reduced the RANKL-induced expression of osteoclastic genes and proteins and transcriptional factors (c-Fos and NFATc1), as well as phosphorylation of mitogen-activated protein kinases (MAPKs). CONCLUSION: FSQTC may inhibit bone destruction of RA by its anti-osteoclastogenic activity both in vivo and in vitro.
35263665 Peroxiredoxin 4 regulates tumor-cell-like characteristics of fibroblast-like synoviocytes 2022 Apr Peroxiredoxin-4 (PRDX4), a member of PRDX family, which played an important role in scavenging reactive oxygen species (ROS). The up-regulation of PRDX4 in synovial tissue and synovial fluid from rheumatoid arthritis (RA) patients has been reported. However, the biological functions of PRDX4 in fibroblast-like synoviocytes (RA-FLS) remains unclear. In this research, we reveal that expression of PRDX4 was notably increased in RA synovial tissue, especially in hyperplastic synovial tissue. PRDX4 silencing significantly inhibited the tumor cell-like behaviors and mRNA expression of matrix metalloproteinases (MMPs) in RA-FLS. Furthermore, overexpression of PRDX4 markedly activated PI3K/Akt signaling pathway, which can be reverted by Akt inhibitor MK-2206. These observations identified elevated PRDX4 may regulates the tumor cell-like biological characteristic of RA-FLS via Pi3k/Akt pathway. Targeting PRDX4 and its downstream signaling pathway might provide a potential diagnostic markers and therapeutic target for RA.
31830807 Genetic polymorphisms of ACE I/D, IL-1β G > A and IL-4 VNTR among Egyptian subjects w 2022 Jun BACKGROUND: Various reports examined the contribution of ACE I/D, IL-1β G > A and IL-4 VNTR with the susceptibility to RA but with conflicting findings. The goal of this study is to assess the impact of these three variants with the susceptibility, clinical and biochemical markers in addition to different composite indices of RA. SUBJECTS AND METHODS: This case-control survey enclosed 120 RA Egyptian patients who were emulated with 150 healthy controls from the same territory. Their genomic DNA was genotyped utilising the PCR approach. RESULTS: RA patients with ACE allele (D) and IL-4 VNTR allele (2 R) were expressively higher emulated with healthy controls (p < .05). Nevertheless, RA patients with IL-1β (A allele) failed to achieve an apparent significant emulated with healthy controls (p > .05). CONCLUSIONS: This work specifies a noteworthy association for ACE I/D and IL-4 VNTR but not IL-1β G > A polymorphisms with RA susceptibility among Egyptian subjects.
35429290 Methotrexate significantly reduces the humoral vaccination response against SARS-CoV-2 in 2022 Jun To assess the humoral response to vaccination against SARS-CoV-2 in patients with rheumatoid arthritis treated with methotrexate (MTX). In total, 142 fully vaccinated individuals were included at 6 ± 1 weeks after their second vaccination [BioNTech/Pfizer (70.4%), AstraZeneca (20.4%), and Moderna (9.2%)]. The primary goal was to assess the humoral immune response as measured by titres of neutralising antibodies against the S1 antigen of SARS-CoV-2. In a cross-sectional, single-centre study, titres were compared between patient subgroups with (n = 80) and without (n = 62) methotrexate exposure. MTX patients showed a significantly reduced humoral response to vaccination in the oldest patient subgroup (> 70 years: P = 0.038), whereas titres of neutralising antibodies were not significantly different between MTX and non-MTX patients in patients less than 70 years of age (< 56 years: P = 0.234; 56-70 years: P = 0.446). In patients > 70 years, non-MTX patients showed a maximum immune response in 76.5% of cases, whereas this percentage was reduced to 53.7% in study participants on MTX medication (effect size d = 0.21). Older age in patients with rheumatoid arthritis in combination with methotrexate results in a significantly reduced humoral response after vaccination against SARS-CoV-2. Our data underline the importance of age regarding the humoral response and may support the temporary cessation of methotrexate, particularly in elderly patients in the context of vaccination against SARS-CoV-2.
35042150 Timing of sinusitis and other respiratory tract diseases and risk of rheumatoid arthritis. 2022 Feb OBJECTIVE: To investigate the association between timing of respiratory tract diseases and risk of rheumatoid arthritis (RA). METHODS: This case-control study using the Mass General Brigham Biobank matched incident RA cases, confirmed by ACR/EULAR criteria, with at least seven years preceding electronic health record (EHR) data to three controls on age, sex, and EHR history from RA diagnosis (index date). We ascertained timing (>0-5 years/>5-10 years/>10 years) of the first documented respiratory tract disease prior to index date using diagnosis codes. We estimated odds ratios (OR) with 95% confidence intervals (CI) for RA for each respiratory exposure using logistic regression models, adjusting for potential confounders. We also conducted a stratified analysis by serostatus and smoking. RESULTS: We identified 625 incident RA cases (median 56 years, 75% female, 57% seropositive) and 1,875 controls. Acute sinusitis was associated with RA only in the >5 to 10 years before RA (OR 3.90, 95% CI:1.90,8.01). In contrast, pneumonia was associated with RA only in the >0 to 5 years before RA (OR 1.73, 95% CI:1.00,3.00), and chronic respiratory tract diseases only >10 years before RA (OR 1.43, 95% CI:1.00,2.05). All respiratory tract diseases tended to show a stronger association with seronegative RA than seropositive RA, although the interaction was statistically significant only for chronic sinusitis (p=0.04). Respiratory diseases showed a nonsignificantly stronger association among smokers than nonsmokers. CONCLUSION: Sinusitis and other respiratory diseases are associated with increased risk of RA, especially 5 years before RA onset. RA may begin many years before clinical onset.
35183936 Drug survival of biologics and novel immunomodulators for rheumatoid arthritis, axial spon 2022 Apr OBJECTIVE: Drug survival is an important proxy measure for effectiveness of treatments for inflammatory diseases such as rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis. The objective of this study was to examine the real-life drug survival of biologics and novel small-molecule therapies across various disease entities such as RA, AxSpA, PsA, and psoriasis. METHODS: We performed a nationwide cohort study using the prospective nationwide registries DANBIO and DERMBIO, comprising all patients treated with biologics or novel small-molecule therapies for RA, AxSpA, PsA, and psoriasis between January 2015 through May 2021 (DANBIO) and November 2009 to November 2019 (DERMBIO). Drug survival was visualized using Kaplan-Meier curves, and Cox proportional hazards models were used to calculate adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs) for risk of discontinuing therapy. FINDINGS: The study comprised a total of 12,089 patients (17,903 treatment series), including 5,104 RA patients (7,867 series), 2,157 AxSpA patients (3,016 series3), 2,551 PsA patients (3,313 series), and 2,577 psoriasis patients (3,707 series). In confounder-adjusted models drug survival in RA was highest for rituximab followed by baricitinib, etanercept and tocilizumab respectively. For AxSpA, drug survival was high for golimumab compared to all other drugs, followed by secukinumab and etanercept and lowest for infliximab. For PsA, tofacitinib and infliximab had the lowest drug survival compared to all other drugs. All other drugs performed almost equally well with a tendency of a somewhat higher drug survival for golimumab, followed by secukinumab and ixekizumab. For psoriasis, drug survival was generally highest for guselkumab. INTERPRETATION: Differing treatment responses to drugs with various modes of action across RA, AxSpA, PsA and psoriasis emphasize that although these diseases have many overlaps in their pathogenesis, there is a need for an individualized treatment approach that considers the underlying disease, patient profile, and treatment history. FUNDING: None.
34057820 Identification of Distinct Disease Activity Trajectories in Methotrexate-Naive Patients Wi 2022 Jan OBJECTIVE: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). To better understand tofacitinib treatment responses, we used group-based trajectory modeling to investigate distinct disease activity trajectories and associated baseline variables in patients with active RA. METHODS: This post hoc analysis used data from a phase III study of methotrexate-naive patients receiving tofacitinib 5 mg twice daily. Changes in the 4-variable Disease Activity Score in 28 joints, using the erythrocyte sedimentation rate (DAS28-ESR) from baseline to month 24 were used in group-based trajectory modeling to identify distinct disease activity trajectories. Patient and disease characteristics, changes in radiographic progression and patient-reported outcomes, and safety up to month 24 were compared among trajectory groups. RESULTS: From 346 methotrexate-naive patients, 5 disease trajectory groups, defined by DAS28-ESR scores, were identified, which progressed from high disease activity (HDA) to remission (group 1, n = 28), to low disease activity (LDA) rapidly (group 2, n = 107), to moderate disease activity (group 3, n = 98), to LDA gradually (group 4, n = 46), or remained in HDA (group 5, n = 67), at month 24. At baseline, groups 1 and 2 generally had lower disease activity and more favorable patient-reported outcomes, compared with other groups. Improvements in radiographic progression and patient-reported outcomes over 24 months were generally consistent with DAS28-ESR-predicted disease activity trajectories. Adverse event rates were generally comparable across groups. CONCLUSION: Distinct phenotypic subgroups identified heterogeneity in patients with RA normally analyzed as a single population. Trajectory modeling may enable separation of clinically meaningful subsets of patients with RA, and may help optimize treatment outcomes.
35288390 Effectiveness and safety of bee venom pharmacopuncture for rheumatoid arthritis: a systema 2022 Mar 14 INTRODUCTION: Rheumatoid arthritis (RA) is the common autoimmune disease with low quality of life. The representative treatment is medication and medication usage has improved through update of clinical guidelines, however, there are still limitations. Bee venom (BV) has been reported to have meaningful therapeutic effects and the possibility of alternative options for RA through several types of studies, but there is no well-organised and recent published systematic review (SR). METHODS: We will search randomised controlled trials about the BV on RA from the inception to 31 May 2022 in various databases, manual research and contacting authors. Electronic databases will include MEDLINE, EMBASE, Cochrane library, China National Knowledge Infrastructure, CiNii, J-STAGE, KoreaMed, Korean Medical Database, Korean Studies Information Service System, National Digital Science Library, Korea Institute of Science and Technology Information and Oriental Medicine Advanced Searching Integrated System. With screening and reviewing process, we will identify the eligible studies and extract the needed data. The primary outcome will be the disease activity scores indicating the improvement of RA symptoms (American College of Rheumatology response criteria 20, 50, 70), functions (Health Assessment Questionnaire, Disease Activity Score of 28 joints), joint (Western Ontario and McMaster universities osteoarthritis index), pain (Visual Analogue Scale, Numerical Rating Scale) and effective rate. The secondary outcomes will be the RA-related blood test levels and adverse events. We will perform a meta-analysis by Review Manager software, the assessment of risk of bias by Cochrane Collaboration 'risk of bias' and the determination of quality of evidence by Grades of Recommendation, Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: Our SR will suggest the clinical evidence of the use of BV for RA to patient, clinicians and policymakers. We will publish our results in a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42021238058.
32961027 Sunlight Exposure, Sun-Protective Behavior, and Anti-Citrullinated Protein Antibody Positi 2022 Feb OBJECTIVE: To examine associations between sunlight exposure and anti-citrullinated protein antibodies (ACPAs) using general population data in Quebec, Canada. METHODS: A random sample of 7,600 individuals (including 786 subjects who were ACPA positive and 201 self-reported rheumatoid arthritis [RA] cases) from the CARTaGENE cohort was studied cross-sectionally. All subjects were nested in 4 census metropolitan areas, and mixed-effects logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) for ACPA positivity related to sunlight exposure, adjusting for sun-block use, industrial fine particulate matter (PM(2.5) ) exposures, smoking, age, sex, French Canadian ancestry, and family income. We also performed sensitivity analyses excluding subjects with RA, defining ACPA positivity by higher titers, and stratifying by age and sex. RESULTS: The adjusted ORs and 95% CIs did not suggest conclusive associations between ACPA and sunlight exposure or sun-block use, but robust positive relationships were observed between industrial PM(2.5) emissions and ACPA (OR 1.19 per μg/m(3) [95% CI 1.03-1.36] in primary analyses). CONCLUSION: We did not see clear links between ACPA and sunlight exposure or sun-block use, but we did note positive associations with industrial PM(2.5) . Future studies of sunlight and RA (or ACPA) should take air pollution exposures into account.
35479077 Epigenetic Regulation of Immune and Inflammatory Responses in Rheumatoid Arthritis. 2022 PURPOSE: Rheumatoid arthritis (RA) is a disease associated with multiple factors. Epigenetics can affect gene expression without altering the DNA sequence. In this study, we aimed to comprehensively analyze epigenetic regulation in RA. METHODS: Using the Gene Expression Omnibus database, we identified a methylation chip, RNA-sequencing, and miRNA microarray for RA. First, we searched for DNA methylation, genes, and miRNAs associated with RA using differential analysis. Second, we determined the regulatory networks for RA-specific methylation, miRNA, and m6A using cross-analysis. Based on these three regulatory networks, we built a comprehensive epigenetic regulatory network and identified hub genes. RESULTS: Using a differential analysis, we identified 16,852 differentially methylated sites, 4877 differentially expressed genes, and 32 differentially expressed miRNAs. The methylation-expression regulatory network was mainly associated with the PI3K-Akt and T-cell receptor signaling pathways. The miRNA expression regulatory network was mainly related to the MAPK and chemokine signaling pathways. M6A regulatory network was mainly associated with the MAPK signaling pathway. Additionally, five hub genes were identified in the epigenetic regulatory network: CHD3, SETD1B, FBXL19, SMARCA4, and SETD1A. Functional analysis revealed that these five genes were associated with immune cells and inflammatory responses. CONCLUSION: We constructed a comprehensive epigenetic network associated with RA and identified core regulatory genes. This study provides a new direction for future research on the epigenetic mechanisms of RA.
35416831 Functionality assessment in patients with rheumatic diseases undergoing treatment in the P 2022 OBJECTIVE: To evaluate the therapeutic response (functionality) and its associated factors in patients on biological drugs on the Public Health System for treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. METHODS: An open prospective cohort was carried out from 2011 to 2019, in Belo Horizonte (MG). Functionality was assessed using the Health Assessment Questionnaire Disability-Index at baseline, and after 6 and 12 months of follow-up. Factors associated with poor functionality were identified through logistic regression. RESULTS: The median Health Assessment Questionnaire Disability-Index at baseline was 1.5 (interquartile range of 0.8-1.9), with poor functionality observed in patients with rheumatoid arthritis. Improved functionality was seen at 6 months of treatment for the three diseases. The predictors of poor functionality at 6 months for psoriatic arthritis and ankylosing spondylitis were female sex, low education levels, and high disease activity; and for rheumatoid arthritis and psoriatic arthritis were female sex, advanced age, and high disease activity. In 12 months, the three diseases had predictors of worse functionality: female sex, low education, and high disease activity. CONCLUSION: There was a significant improvement in functionality during the follow-up, with better response at 6 months of treatment. Poor functionality was observed in older, female patients, with low education and high disease activity.
35440905 Patient-based benefit-risk assessment of medicines: development, refinement, and validatio 2022 Apr 1 INTRODUCTION: Poor indexing and inconsistent use of terms and keywords may prevent efficient retrieval of studies on the patient-based benefit-risk assessment (BRA) of medicines. We aimed to develop and validate an objectively derived content search strategy containing generic search terms that can be adapted for any search for evidence on patient-based BRA of medicines for any therapeutic area. METHODS: We used a robust multistep process to develop and validate the content search strategy: (1) we developed a bank of search terms derived from screening studies on patient-based BRA of medicines in various therapeutic areas, (2) we refined the proposed content search strategy through an iterative process of testing sensitivity and precision of search terms, and (3) we validated the final search strategy in PubMed by firstly using multiple sclerosis as a case condition and secondly computing its relative performance versus a published systematic review on patient-based BRA of medicines in rheumatoid arthritis. RESULTS: We conceptualized a final search strategy to retrieve studies on patient-based BRA containing generic search terms grouped into two domains, namely the patient and the BRA of medicines (sensitivity 84%, specificity 99.4%, precision 20.7%). The relative performance of the content search strategy was 85.7% compared with a search from a published systematic review of patient preferences in the treatment of rheumatoid arthritis. We also developed a more extended filter, with a relative performance of 93.3% when compared with a search from a published systematic review of patient preferences in lung cancer.
34806241 AGER gene variant as a risk factor for juvenile idiopathic arthritis. 2022 Feb BACKGROUND: The AGER gene encodes a cell surface multiligand receptor of advanced glycation end-products that is also capable of binding other molecules and is involved in numerous pathways related to inflammation, apoptosis, immunity and so on. In the present study, we aimed to investigate whether the AGER rs1035798 (G>A) intronic polymorphism, showing an association with multiple sclerosis and rheumatoid arthritis in adults, is related to juvenile idiopathic arthritis (JIA). METHODS: Caucasian children from the Belarusian population were enrolled in the study. In total, there were 201 cases with JIA, 37 with juvenile systemic lupus erythematosus, 222 children with the articular syndrome of non-autoimmune etiology (positive control for JIA) and 365 negative controls (children without any autoimmune or inflammatory diseases). Genomic DNA samples from the patients and controls were genotyped by a real-time polymerase chain reaction. RESULTS: A marked association of the homozygous AA rs1035798 genotype with JIA (p = 5 × 10(-4) ) was found. Allele A was also associated with JIA (p = 0.0058), as well as with the articular syndrome of non-autoimmune etiology (p = 0.0264). The highest frequencies of the AA genotype were found in the subgroups of JIA patients with polyarthritis or severe oligoarthritis. The AA genotype patients also had the smallest mean age of the JIA onset. CONCLUSIONS: Our results demonstrate that the AGER rs1035798 AA genotype is a risk factor for JIA in Belarusian children. They also suggest a link between the AGER AA genotype and the risk of JIA early onset and severity. However, the functional relevance of the rs1035798 polymorphism is still unclear.
34279701 Oral health-related quality of life in patients with early rheumatoid arthritis is associa 2022 Jan OBJECTIVES: To evaluate oral health-related quality of life (OHRQoL) in early rheumatoid arthritis (ERA) patients and individuals at risk of rheumatoid arthritis (RA) compared to healthy controls, and to explore possible associated factors. MATERIALS AND METHODS: Fifty ERA patients, 50 at-risk individuals, and 50 age and gender matched healthy controls were recruited. OHRQoL (Oral Health Impact Profile-14 (OHIP-14)); number of decayed, missing, and filled teeth (DMFT); denture use; periodontal inflamed surface area (PISA); xerostomia (xerostomia inventory (XI)); and possible TMD (-pain) diagnoses were recorded. The groups were compared on these variables. Subsequently, backward multiple regression analyses were performed for the ERA and at-risk groups, with OHRQoL as the dependent variable and gender, age, DMFT, denture use, PISA, XI, non-painful TMD, and TMD pain as independent variables. RESULTS: At-risk individuals had higher XI scores (U = 789.5, z = -3.181, p = 0.001, r = -0.32) and higher prevalence of TMD pain (p = 0.046, OR = 4.57; 95% CI 0.92-22.73) than healthy controls and higher OHIP-14 scores than the ERA group (U = 894.5, z = -2.418, p = 0.016, r = -0.24), while no difference in OHIP-14 was found between the control group and both other groups. For ERA patients, OHRQoL was associated with PISA and TMD pain (R(2) = 0.498, p < 0.001). For at-risk individuals, OHRQoL was associated with XI score (R(2) = 0.410, p < 0.001). CONCLUSIONS: Alertness of health professionals to TMD pain and periodontal inflammation in ERA patients and to xerostomia and TMD pain in at-risk individuals is recommended. CLINICAL RELEVANCE: The results of this study address orofacial aspects that require attention of health professionals in the timeframe around RA onset. TRIAL REGISTRATION: Dutch National Trial Register (NTR, NTR6362).
35478104 Clinical Importance of Body Composition in Improving Bone Mineral Density of Femoral Neck 2022 May BACKGROUND/AIM: To investigate factors associated with increased bone mineral density (BMD) of the neck of femur in rheumatoid arthritis or collagen diseases receiving denosumab, focusing on body composition calculated by bioelectrical impedance analysis (n=90, 78 females). PATIENTS AND METHODS: We defined Δfemur as BMD (12 months minus baseline), using dual-energy X-ray absorptiometry after denosumab therapy. Factors associated with Δfemur were retrospectively investigated. RESULTS: Low skeletal muscle index (SMI) was observed in 6 males and 32 females. There was a significant difference in phase angle (PhA) of the left leg (LL) between the Δfemur ≥0 (n=70) and Δfemur <0 (n=20) groups (p=0.040) but not in SMI (p=0.310). Multiple regression analysis indicated that PhA of LL was significantly related to Δfemur (p=0.0398). CONCLUSION: PhA appears to be a clinically significant indicator of improvement of Δfemur in patients receiving denosumab.