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ID PMID Title PublicationDate abstract
34505214 Sustainable positive effects of Ramadan intermittent fasting in rheumatoid arthritis. 2022 Feb The short-term positive effects of intermittent fasting during the month of Ramadan on rheumatic inflammatory diseases have been previously evaluated. The objective of this study was to assess the sustainability of these effects on rheumatoid arthritis (RA) activity. This prospective study included 35 patients with RA, who observed fasting during Ramadan 2019. The disease activity was assessed and compared between three time points: T1 (6 months before the beginning of Ramadan), T2 (during the month between the 7th day of fasting and the 7th day after Ramadan), and T3 (averagely 3.4 months after fasting). The disease activity score 28 (DAS28) was used to evaluate the disease activity. After a significant decrease of all disease activity parameters between T1 and T2, a gradual increase of clinical and biological outcomes was seen between T2 and T3. Except for CRP, which was significantly higher at T3 (p = 0.02), the changes of the other disease activity parameters were not statistically significant. By reference to baseline data (T1), the decrease of ESR, DAS28 CRP, and DAS28 ESR induced after Ramadan fast was maintained until T3, with statistically significant differences. We can therefore conclude that this study has been conducted at the beginning of the fading-out of the effects of Ramadan fast, and that the duration of 3 months may be the recommended interval between fasting periods to maintain the positive effects of intermittent fasting on RA activity. Key Points • Intermittent fasting can induce a rapid improvement of rheumatoid arthritis activity. • The positive effects of this model of fasting can last up to 3 months. • The recommended interval between fasting periods may be estimated at 3 months.
34221300 An Efficient CNN for Hand X-Ray Classification of Rheumatoid Arthritis. 2021 Hand Radiography (RA) is one of the prime tests for checking the progress of rheumatoid joint inflammation in human bone joints. Recognizing the specific phase of RA is a difficult assignment, as human abilities regularly curb the techniques for it. Convolutional neural network (CNN) is the center for hand recognition for recognizing complex examples. The human cerebrum capacities work in a high-level way, so CNN has been planned depending on organic neural-related organizations in humans for imitating its unpredictable capacities. This article accordingly presents the convolutional neural network (CNN) which has the ability to naturally gain proficiency with the qualities and anticipate the class of hand radiographs from an expansive informational collection. The reproduction of the CNN halfway layers, which depict the elements of the organization, is likewise appeared. For arrangement of the model, a dataset of 290 radiography images is utilized. The result indicates that hand X-rays are rated with an accuracy of 94.46% by the proposed methodology. Our experiments show that the network sensitivity is observed to be 0.95 and the specificity is observed to be 0.82.
33162271 Risk Factors Contributing to Early Implant Fracture in Silicone Metacarpophalangeal Joint 2021 Mar PURPOSE: To identify the risk factors associated with early implant fracture of silicone metacarpophalangeal (MCP) joint arthroplasty using the volar hinge silicone implant for patients with rheumatoid arthritis. METHODS: We retrospectively reviewed 113 fingers of 31 hands that underwent MCP joint arthroplasty between 2008 and 2014, with a minimum follow-up of 3 years,. An implant fracture within 3 years after surgery was regarded as an early implant fracture. Patient records were reviewed for potential risk factors of age, affected fingers, ulnar drift angle, and range of motion of the MCP joint before surgery and 1 year after surgery. Candidate risk factors were compared at the level of the digit and at the patient level. RESULTS: With fracture of the implants as the end point, Kaplan-Meier estimated survival rate was 74.3% at 3 years and 67.9% at 5 years. Early implant fracture was detected in 29 fingers. Bivariate analyses showed significant associations between early implant fracture and MCP joint arc of motion before surgery, MCP joint flexion range 1 year after surgery, and MCP joint arc of motion 1 year after surgery. Multiple logistic regression analysis showed that increased MCP joint flexion range 1 year after surgery was an independent risk factor for early implant fracture. CONCLUSIONS: Increasing MCP joint flexion range was associated with increased fractures of the implants. We propose that the MCP joint flexion range should be restricted to less than 60° in postoperative rehabilitation; it is necessary to educate the patient to permanently avoid excessive flexion of the MCP joint. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
33605085 Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis. 2021 Aug OBJECTIVE: Collectin 11 (CL-11) is a soluble C-type lectin, a mediator of innate immunity. Its role in autoimmune disorders is unknown. We undertook this study to determine the role of CL-11 in a mouse model of rheumatoid arthritis (RA). METHODS: A murine collagen-induced arthritis (CIA) model was used and combined two approaches, including gene deletion of Colec11 and treatment with recombinant CL-11 (rCL-11). Joint inflammation and tissue destruction, circulating levels of inflammatory cytokines, and adaptive immune responses were assessed in mice with CIA. Splenic CD11c+ cells were used to examine the influence of CL-11 on antigen-presenting cell (APC) function. Serum CL-11 levels in RA patients were also examined. RESULTS: Colec11(-/-) mice developed more severe arthritis than wild-type mice, as determined by disease incidence, clinical arthritis scores, and histopathology (P < 0.05). Disease severity was associated with significantly enhanced APC activation, Th1/Th17 responses, pathogenic IgG2a production and joint inflammation, as well as elevated circulating levels of inflammatory cytokines. In vitro analysis of CD11c+ cells revealed that CL-11 is critical for suppression of APC activation and function. Pharmacologic treatment of mice with rCL-11 reduced the severity of CIA in mice. Analysis of human blood samples revealed that serum CL-11 levels were lower in RA patients (n = 51) compared to healthy controls (n = 53). Reduction in serum CL-11 was inversely associated with the Disease Activity Score in 28 joints, erythrocyte sedimentation rate, and C-reactive protein level (P < 0.05). CONCLUSION: Our findings demonstrate a novel role of CL-11 in protection against RA, suggesting that the underlying mechanism involves suppression of APC activation and subsequent T cell responses.
33495387 Multidisciplinary team intervention to reduce the nocebo effect when switching from the or 2021 Jan OBJECTIVES: To evaluate an intervention to reduce the nocebo effect (NE) when switching from the originator infliximab (OI) to the infliximab biosimilar SB2 in chronic inflammatory rheumatic disease (CIRD). METHODS: An intervention was built with healthcare professionals (HPs) and a patient representative, based on a systematic review of interventions reducing the NE in musculoskeletal diseases and semi-directed questioning of five patients. Our strategy consisted of training HPs, switch information given by the nurses, a consistent vocabulary. All CIRD patients switched from OI to SB2 were included for the intervention. The primary outcome was the SB2 retention rate (RR) at 34 weeks. Secondary outcomes were the SB2 RR at 12 months, discontinuation rates due to a possible NE and comparison with a historical cohort of CIRD patients receiving the OI and 6 published European cohorts. RESULTS: 45 patients were included from March 2018 (rheumatoid arthritis, n=17, spondylarthritis, n=28). After 34 weeks, the SB2 RR was 91.2%, similar to the historical cohort RR (p=0.41) but higher than the 3 European cohort RRs (p<0.05). At 12 months, the SB2 RR was 84.5% vs 88.4% for the historical cohort (p=0.52). SB2 discontinuation due to a possible NE was 6.6% after 12 months. CONCLUSIONS: A tailored communication with a prominent role of nurses reduced the NE in non-medical switches from the OI to SB2 as compared to published results. The RR was similar to the historical cohort RR. The methodology used to construct this intervention may help improve the outcomes of switches with upcoming biosimilars.
33944642 JAK inhibitors, psoriatic arthritis, and axial spondyloarthritis: a critical review of cli 2021 Jul INTRODUCTION: Psoriatic arthritis (PsA) and spondyloarthritis (SpA) are inflammatory arthritides associated with progressive damage, deformity and morbidity. Janus kinase (JAK) inhibitors block JAKs, cytoplasmic protein tyrosine kinases important in signal transduction and immune processes that are currently being studied as synthetic disease modifying anti-rheumatic drugs (tsDMARDs) in psoriatic arthritis and spondyloarthritis. AREAS COVERED: This review evaluates published phase 2 and 3 clinical trial data for JAK kinase inhibitors for psoriatic arthritis and spondyloarthritis. A literature search using PubMed was conducted using the following keywords: 'psoriatic arthritis', 'ankylosing spondylitis', 'axial spondyloarthritis', 'non-radiographic axial spondyloarthritis', 'tofacitinib', 'baricitinib', 'filgotinib' and 'upadacitinib'. Mechanism of action, phase 2 and 3 clinical trial data, including efficacy and safety, are discussed. EXPERT OPINION: JAK inhibitors are important orally administered agents conferring different degrees of selectivity toward JAK1, JAK2, and JAK3 which may have implications on efficacy and safety in PsA and SpA. Phase 2 and 3 clinical trials in PsA for tofacitinib and upadacitinib and phase 2 for filgotinib confirmed efficacy comparable to biologic DMARDs. In SpA, phase 2 and 2/3 studies confirmed significant efficacy of tofacitinib, filgotinib and upadacitinib compared to placebo. Safety was comparable to clinical trial, long-term extension, and registry data for rheumatoid arthritis.
33879788 Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-i 2021 Apr 20 In healthy joints, synovial fibroblasts (SFs) provide the microenvironment required to mediate homeostasis, but these cells adopt a pathological function in rheumatoid arthritis (RA). Carbohydrates (glycans) on cell surfaces are fundamental regulators of the interactions between stromal and immune cells, but little is known about the role of the SF glycome in joint inflammation. Here we study stromal guided pathophysiology by mapping SFs glycosylation pathways. Combining transcriptomic and glycomic analysis, we show that transformation of fibroblasts into pro-inflammatory cells is associated with glycan remodeling, a process that involves TNF-dependent inhibition of the glycosyltransferase ST6Gal1 and α2-6 sialylation. SF sialylation correlates with distinct functional subsets in murine experimental arthritis and remission stages in human RA. We propose that pro-inflammatory cytokines remodel the SF-glycome, converting the synovium into an under-sialylated and highly pro-inflammatory microenvironment. These results highlight the importance of glycosylation in stromal immunology and joint inflammation.
34486098 Adaptation of a Shared Decision-Making Tool for Early Rheumatoid Arthritis Treatment Decis 2022 Mar BACKGROUND: Patient decision aids (PtDAs) enable shared decision-making between patients and healthcare providers. Adaptations to PtDAs for use with populations facing inequities in healthcare can improve the relevancy of information presented, incorporate appropriate cultural context, and address health literacy concerns. Our objective was to adapt the Early RA (rheumatoid arthritis) PtDA for use with Canadian Indigenous patients. METHODS: The Early RA PtDA was modified through an iterative process using data obtained from semi-structured interviews of two sequential cohorts of Indigenous patients with RA. Interview data were analyzed using thematic analysis. RESULTS: Seven participants provided initial feedback on the existing PtDA. The modifications they suggested were made and shared with another nine participants to confirm acceptability and provide further feedback. The first cohort suggested revisions to clarify medical and cost coverage information, include Indigenous traditional healing practice options, simplify text, and include Indigenous images and colors aligned with Canadian Indigenous community representation. Additional revisions were suggested by the second cohort to increase the legibility of the text, insert more Indigenous imagery, address formulary coverage for non-status First Nations patients, and include information about lifestyle factors in managing RA. CONCLUSION: Incorporating Indigenous-specific adaptations in the design of PtDAs may increase use and relevancy to support engagement in treatment decisions, thereby supporting health-equity oriented health service interventions. Indigenous patient-specific evidence and translation of key words into the end-users' Indigenous languages should be included for implementation of the PtDA.
34755662 [Effects of Sidaxue, a Miao ethnomedicine recipe, on apoptosis and pyrolysis of human fibr 2021 Oct 20 OBJECTIVE: To investigate the effects of Sidaxue (SX), a recipe in Miao ethnomedicine, on apoptosis and pyrolysis of human fibroblast-like synovial cells in rheumatoid arthritis (RA-FLS). METHODS: The target proteins related with RA and those involved in cell apoptosis and pyroptosis were searched in different online databases, and Venny software was used to obtain apoptosis- and pyroptosis-related proteins in RA. RA-apoptosis-pyroptosis protein interaction (PPI) network was constructed to identity the key target proteins related with apoptosis and pyroptosis in RA. Autodock vina software was used to perform molecular docking to verify the binding ability of the main active ingredients in SX with the apoptosis- and pyroptosis-related proteins. In the cell experiment, MH7A cells were treated with 5 mg/L TGT (positive control) or 5, 10, 20, and 40 mg/L SX, and the changes in cell migration and invasion abilities and expressions of apoptosis- and pyroptosis-related proteins were examined using wound healing assay, Transwell assay, ELISA and Western blotting. RESULTS: We identified 9 RA-related apoptotic target proteins, 15 RA-related pyroptosis target proteins, and 4 overlapping target proteins related with RA, apoptosis and pyroptosis. The main active ingredients in SX had a high affinity with the target proteins including TNF-α, Fas, and Bax. In MH7A cells, SX treatment concentration-dependently increased the cell inhibition rate at 24, 48 and 72 h (P < 0.05), and significantly lowered the cell migration ability at 6, 12 and 24 h (P < 0.05); treatment with 20 and 40 mg/L SX for 24 h obviously suppressed MH7A cell invasion (P < 0.05). SX treatment (20 and 40 mg/L) and TGT treatment both significantly lowered the expression levels of TNF-α, IL-1β, and IL-18 in the cells (P < 0.05). The Bax/Bcl-2 ratio and Fas and FasL expressions were increased significantly in cells treated with 20 and 40 mg/L SX (P < 0.05), and caspase-1 expression was decreased significantly in cells treated with 5 and 40 mg/L SX (P < 0.05). CONCLUSION: SX can induce apoptosis and pyroptosison in RA-FLSs possibly by down-regulating the expressions of TNF-α, IL-1β and IL-18, up-regulating the expressions of Bax, Fas, and FasL, and inhibiting Bcl-2 and caspase-1 protein expressions.
34134125 Chinese registry of rheumatoid arthritis: IV. Correlation and consistency of rheumatoid ar 2021 Jun 20 BACKGROUND: Disease activity indices (DAIs) including disease activity score 28 (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) have been widely used in clinical practice and research studies of rheumatoid arthritis (RA). The objective of our study was to evaluate the correlation and concordance among different DAIs in Chinese patients with RA. METHODS: A cross-sectional study, including patients enrolled in the Chinese registry of rheumatoid arthritis from November 2016 to August 2018, was conducted. The correlations were evaluated using Spearman correlation coefficient and concordance with Bland-Altman plots, quadratic weighted kappa, and discordance rates in the crosstab. For other indices, the optimal cutoff points corresponding to SDAI remission were explored through receiver operating characteristic curve analysis. RESULTS: A total of 30,501 patients were included, of whom 80.46% were women. Most individuals were with moderate disease activity or high disease activity. High correlations among DAS28-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP), SDAI and CDAI were observed. Similarly, the weighted kappa value among the indices was high. In Bland-Altman plots, a positive difference between DAS28-ESR and DAS28-CRP was observed, with an absolute difference of >1.2 in 3079 (10.09%) patients. In crosstab, approximately 30% of the patients were classified into different groups. Concordance values between SDAI remission and the optimal cutoff points of DAS28-ESR, DAS28-CRP, and CDAI were 3.06, 2.37, and 3.20, respectively. CONCLUSIONS: Although DAIs had high correlations and weighted kappa values, the discordance between DAIs was significant in Chinese patients with RA. The four DAIs are not interchangeable.
33748831 Doppler ultrasound predicts successful discontinuation of biological DMARDs in rheumatoid 2021 Dec 1 OBJECTIVE: To assess the ability of ultrasound to predict successful tapering and successful discontinuation of biological DMARDs (bDMARDs) at the 2-year follow-up in RA patients in sustained remission. METHODS: Patients in sustained remission (DAS28-CRP ≤ 2.6) and with no radiographic progression the previous year tapered bDMARDs according to a standardized regime. A total of 119 of these patients were included in this ultrasound substudy. At baseline, clinical assessment, MRI, X-ray and ultrasound of 24 joints were performed. Ultrasound-detected synovitis was defined and scored 0-3 using the OMERACT scoring system at the joint level for both grey-scale and Doppler activity. Sum scores for each ultrasound modality were calculated for 24 joints at the patient level. The final state of treatment was assessed after 2 years. The predictive value of ultrasound measures for successful tapering and discontinuation at the 2-year follow-up was assessed via logistic regression analyses. RESULTS: Negative IgM-RF [odds ratio (OR) = 0.29, 95% CI: 0.10-0.85; P = 0.024] and lower Doppler sum score of 24 joints (OR = 0.44, 95% CI: 0.15, 0.87; P = 0.014) were independent predictors for successful discontinuation of bDMARDs at the 2-year follow-up. The predictive value of the Doppler sum score was independent of MRI findings. Previous numbers of bDMARDs were predictive of successful tapering (OR = 0.58, 95% CI: 0.35, 0.91; P = 0.018), whereas ultrasound was not. Clinical parameters were not predictive of successful tapering/discontinuation. CONCLUSION: Doppler sum score was an independent predictor for successful discontinuation of bDMARDs at the 2-year follow-up-the odds for achieving successful discontinuation decreased by 56% per one-unit increase in Doppler sum score. Ultrasound could not predict successful tapering.
33444321 Diminished cytokine-induced Jak/STAT signaling is associated with rheumatoid arthritis and 2021 Rheumatoid arthritis (RA) is a systemic and incurable autoimmune disease characterized by chronic inflammation in synovial lining of joints. To identify the signaling pathways involved in RA, its disease activity, and treatment response, we adapted a systems immunology approach to simultaneously quantify 42 signaling nodes in 21 immune cell subsets (e.g., IFNα→p-STAT5 in B cells) in peripheral blood mononuclear cells (PBMC) from 194 patients with longstanding RA (including 98 patients before and after treatment), and 41 healthy controls (HC). We found multiple differences between patients with RA compared to HC, predominantly in cytokine-induced Jak/STAT signaling in many immune cell subsets, suggesting pathways that may be associated with susceptibility to RA. We also found that high RA disease activity, compared to low disease activity, was associated with decreased (e.g., IFNα→p-STAT5, IL-10→p-STAT1) or increased (e.g., IL-6→STAT3) response to stimuli in multiple cell subsets. Finally, we compared signaling in patients with established, refractory RA before and six months after initiation of methotrexate (MTX) or TNF inhibitors (TNFi). We noted significant changes from pre-treatment to post-treatment in IFNα→p-STAT5 signaling and IL-10→p-STAT1 signaling in multiple cell subsets; these changes brought the aberrant RA signaling profiles toward those of HC. This large, comprehensive functional signaling pathway study provides novel insights into the pathogenesis of RA and shows the potential of quantification of cytokine-induced signaling as a biomarker of disease activity or treatment response.
34237693 A systematic review and meta-analysis of observational studies on the association between 2021 Jul OBJECTIVE: The aim of this study was to investigate the linear and nonlinear dose-response associations of animal-based dietary protein intake and risk of developing rheumatoid arthritis (RA). METHODS: A systematic search of MEDLINE, Scopus and Embase was conducted up to October 2020. Observational studies that report risk estimates of RA for animal-based protein consumption were included. We calculated pooled relative risks (RRs) by using a random-effects model. Linear and non-linear dose-response analyses were performed to examine the dose-response relations between animal-based protein consumption and RA. RESULTS: Seven cohort studies (n = 457,554) with 3545 incident cases and six case-control studies with 3994 cases and 5252 controls were identified. Highest compared with the lowest category of fish consumption was inversely associated with risk of RA (RR: 0.89; 95% CI, 0.80 to 0.99; I(2) = 0%, n = 10). Also, a 100 g/day increment in fish intake was associated with a 15% decreased risk of RA. Dose-response analysis showed a modest U-shaped association between fish consumption and incidence of RA, with the lowest risk at a fish intake of 20-30 g/day (P(non-linearity) = 0.04). We found no significant association between consumption of red meat, poultry or dairy and the risk of RA. CONCLUSION: The present study revealed a significant reverse association between fish consumption and risk of RA. While we observed no association between red meat, dairy or poultry consumption and risk of RA. Further well-designed prospective studies are needed to support our findings.
34358861 Triptolide decreases rheumatoid arthritis fibroblast-like synoviocyte proliferation, invas 2021 Oct OBJECTIVE: Our previous study observed that long non-coding RNA (lncRNA) RP11-83J16.1 promoted rheumatoid arthritis (RA)-fibroblast-like synoviocyte (RA-FLS) proliferation, invasion and inflammation, which was downregulated by triptolide treatment. Therefore, the present study aimed to further investigate the mechanism and interaction between triptolide and lncRNA RP11-83J16.1 in RA treatment in vitro and in vivo. METHODS: RA-FLS was isolated and treated by different concentration of triptolide and lncRNA RP11-83J16.1 overexpression plasmid. Furthermore, collagen-induced arthritis (CIA) rat model was constructed followed by triptolide and lncRNA RP11-83J16.1 overexpression plasmid treatment. RESULTS: Triptolide inhibited RA-FLS viability and lncRNA RP11-83J16.1 expression in a dose-dependent manner. Afterward, triptolide treatment inhibited RA-FLS proliferation, invasion, levels of inflammatory markers (TNF-α, IL-1β, IL-6, MMP-3, and MMP-9), inactivated lncRNA RP11-83J16.1, URI1 and β-catenin signaling, but promoted apoptosis. However, lncRNA RP11-83J16.1 overexpression weakened the effects of triptolide on regulating RA-FLS cell behaviors, URI1 signaling and β-catenin signaling. In CIA model, triptolide decreased arthritis score, hyperproliferation of synovial cells, inflammation infiltration of synovial tissue, inflammatory markers (TNF-α, IL-1β, IL-6, MMP-3, and MMP-9), inactivated lncRNA RP11-83J16.1, URI1 and β-catenin signaling, but increased cell apoptosis rate of synovial tissue. Nevertheless, lncRNA RP11-83J16.1 curtailed the treatment effect of triptolide in CIA model. CONCLUSION: Triptolide decreases RA-FLS proliferation, invasion, inflammation and presents a therapeutic effect in CIA model via inactivating lncRNA RP11-83J16.1 mediated URI1 and β-catenin signaling.
34412722 Adherence to the dietary approaches to stop hypertension dietary pattern and rheumatoid ar 2021 Dec OBJECTIVE: To examine the hypothesis that rheumatoid arthritis (RA) patients are less likely than healthy individuals to adhere to the dietary approaches to stop hypertension (DASH) dietary pattern. DESIGN: A multi-centre cross-sectional study involving a total of 300 eligible Iranian adults (aged >19 years; 93·0 % female) recruited during 2019-2020. Participants' actual dietary intakes were measured via self-administered 3-d dietary records. The DASH score was computed based on the energy-adjusted intakes of eight major dietary components usually emphasised (i.e. fruits, vegetables, nuts and legumes, low-fat dairy products and whole grains) or minimised (i.e. sweets, red or processed meats and sodium) in the DASH diet. The higher the DASH score of subjects, the greater their adherence to the DASH pattern. SETTING: The outpatient clinics of major general hospitals in Shiraz, Iran. PARTICIPANTS: 100 incident cases with definite RA according to the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA and 200 apparently healthy controls frequency-matched by gender and age. RESULTS: After adjusting for several potential covariates in the binary logistic regression analysis, RA cases were less likely than controls to have high adherence to the DASH pattern (OR = 0·08; 95 % CI 0·03, 0·20; P = 0·001). CONCLUSIONS: Our findings in a sample of Iranian adults revealed that RA patients are less likely than healthy individuals to adhere to the DASH dietary pattern. However, the potential causal association of greater adherence to the DASH pattern and lower risk of RA needs to be confirmed by prospective studies of high methodological quality.
33589546 Similarity of Response to Biologics Between Elderly-onset Rheumatoid Arthritis (EORA) and 2021 Nov OBJECTIVE: Increasing numbers of patients are developing rheumatoid arthritis (RA) at an older age, and optimal treatment of patients with elderly-onset RA (EORA) is attracting greater attention. This study aimed to analyze the efficacy and safety of biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in EORA and non-EORA elderly patients. METHODS: A cohort of patients with RA treated with b/tsDMARDs were retrospectively analyzed. Only patients aged ≥ 60 years were included. Among them, patients who developed RA aged ≥ 60 years were categorized as EORA, whereas those aged < 60 years were categorized as non-EORA elderly. Disease activity was compared between the EORA and non-EORA elderly groups. RESULTS: In total, 1040 patients were categorized as EORA and 710 as non-EORA elderly. There were no significant differences in characteristics at baseline between the 2 groups. The proportion of patients with low and high disease activity was comparable at Weeks 2, 22, and 54 between the EORA and the non-EORA elderly group. There were no significant differences in the reasons for the discontinuation of b/tsDMARDs between the 2 groups. Elderly RA onset did not affect changes in Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index, nor did it affect the reasons for b/tsDMARD discontinuation between the 2 groups. The trajectory analysis on CDAI responses to b/tsDMARDs for 54 weeks identified 3 response patterns. The proportion of patients categorized into each group and CDAI response trajectories to b/tsDMARDs were very similar between EORA and non-EORA elderly patients. CONCLUSION: CDAI response patterns to b/tsDMARDs and HR of adverse events were similar between EORA and non-EORA elderly patients.
34866331 Gene polymorphisms of SIRT1 in patients with rheumatoid arthritis. 2022 Feb AIM: Previous studies have shown that silent information regulator 1 (SIRT1) expression is elevated in rheumatoid arthritis (RA) patients. However, whether gene polymorphisms in SIRT1 gene associated with RA in a Chinese Han population remains to be discussed. METHOD: In this case-control study, 529 RA patients and 700 healthy controls were selected, and association of 11 SIRT1 gene polymorphisms (rs12415800, rs3740051, rs932658, rs3740053, rs7895833, rs10509291, rs33957861, rs7069102, rs2273773, rs3818292, rs1467568) with RA susceptibility was evaluated. RESULTS: Frequency of GA+GG genotype of rs3740051 in RA patients was significantly lower than that in healthy controls (P = .037). Frequencies of GC and GC+GG genotypes of rs7069102 were significantly lower than those in healthy controls (P = .036, P = .047). Frequencies of GA and GA+GG genotypes of rs1467568 were lower in RA patients as compared to those in healthy controls (P = .011, P = .013). For rs2273773, RA patients who carried the T allele had higher number of tender joints than patients who carried the C allele (P = .033). Other polymorphisms did not associate with RA risk. CONCLUSION: The findings suggest that rs3740051, rs7069102 and rs1467568 variants in SIRT1 gene are related to RA susceptibility in a Chinese Han population.
34147915 Celastrol inhibits rheumatoid arthritis through the ROS-NF-κB-NLRP3 inflammasome axis. 2021 Sep Emerging evidence indicates that NOD-like receptor protein 3 (NLRP3) inflammasome-induced inflammation plays a critical role in the pathogenesis of rheumatoid arthritis (RA). Celastrol (Cel) is a quinone-methylated triterpenoid extracted from Tripterygium wilfordii that is used to treat RA. However, researchers have not determined whether Cel exerts anti-RA effects by regulating the activation of the NLRP3 inflammasome. In the present study, complete Freund's adjuvant (CFA)- induced rats and human mononuclear macrophages (THP-1 cells) were used to explore the anti-RA effects of Cel and its underlying mechanism. Joint swelling, the arthritis index score, inflammatory cell infiltration, and synovial hyperplasia in CFA-induced rats were correspondingly reduced after Cel treatment. The secretion of interleukin (IL)-1β and IL-18 in the serum of CFA-induced rats and supernatants of THP-1 cells exposed to Cel was significantly decreased. These inhibitory effects occurred because Cel blocked the nuclear factor-kappa B (NF-κB) signaling pathway and inhibited the activation of the NLRP3 inflammasome. Furthermore, Cel inhibited reactive oxygen species (ROS) production induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). We speculated that Cel relieves RA symptoms and inhibits inflammation by inhibiting the ROS-NF-κB-NLRP3 axis.
33001576 Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis. 2021 Mar OBJECTIVE: Eicosanoids modulate inflammation via complex networks involving different pathways and downstream mediators, including oxylipins. Although altered eicosanoids are linked to rheumatoid arthritis (RA), suggesting that metabolization is enhanced, the role of oxylipins in disease stratification remains unexplored. This study was undertaken to characterize oxylipin networks during the earliest stages of RA and evaluate their associations with clinical features and treatment outcomes. METHODS: In total, 60 patients with early RA (according to the American College of Rheumatology/European League Against Rheumatism 2010 criteria), 11 individuals with clinically suspect arthralgia (CSA), and 28 healthy control subjects were recruited. Serum samples were collected at the time of onset. In the early RA group, 50 patients who had not been exposed to disease-modifying antirheumatic drug (DMARD) or glucocorticoid treatment at the time of recruitment were prospectively followed up at 6 and 12 months after having received conventional synthetic DMARDs. A total of 75 oxylipins, mostly derived from arachidonic, eicosapentanoic, and linoleic acids, were identified in the serum by liquid chromatography tandem mass spectrometry. RESULTS: Univariate analyses demonstrated differences in expression patterns of 14 oxylipins across the RA, CSA, and healthy control groups, with each exhibiting a different trajectory. Network analyses revealed a strong grouping pattern of oxylipins in RA patients, whereas in individuals with CSA, a fuzzy network of oxylipins with higher degree and closeness was found. Partial least-squares discriminant analyses yielded variable important projection scores of >1 for 22 oxylipins, which allowed the identification of 2 clusters. Cluster usage differed among the groups (P = 0.003), and showed associations with disease severity and low rates of remission at 6 and 12 months in RA patients who were initially treatment-naive. Pathway enrichment analyses revealed different precursors and pathways between the groups, highlighting the relevance of the arachidonic acid pathway in individuals with CSA and the lipooxygenase pathway in patients with early RA. In applying distinct oxylipin signatures, subsets of seropositive and seronegative RA could be identified. CONCLUSION: Oxylipin networks differ across stages during the earliest phases of RA. These distinct oxylipin networks could potentially elucidate pathways with clinical relevance for disease progression, clinical heterogeneity, and treatment response.
32548773 Renal disorders in rheumatologic diseases: the spectrum is changing (part 2. Arthridides). 2021 Aug This review is devoted to rheumatologic diseases mainly characterized by different types of arthritis. They may involve also different organs, including the kidney, but renal disease is more frequently caused by the nephrotoxicity of drugs to relieve pain or to interfere with the pathophysiology of the underlying disease. Rheumatoid arthritis is the prototype of arthropathies. This autoimmune disease mainly attacks joints, tendons and ligaments but can also involve internal organs including the kidney. Psoriatic arthritis is a complex disease in which psoriasis, a chronic inflammatory disease, is associated with the development of peripheral arthritis or spondylitis. The disease or its treatment may lead to kidney complications. Gout is a form of inflammatory arthritis which is characterized by an increase in the serum uric acid deposits in and around the joints of the extremities, the so called tophi. The disease is often associated with a metabolic syndrome with diabetes, obesity, hypertension, and cardiovascular disease. Kidney injury is frequent. It may be caused by kidney stones, urinary tract obstruction, tubulointerstitial and vascular lesions leading to CKD and renal failure.