Browse

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

ID PMID Title PublicationDate abstract
34788483 Blood MALT1, Th1, and Th17 cells are dysregulated, inter-correlated, and correlated with d 2022 Jan OBJECTIVE: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) participates in inflammatory and autoimmune diseases via activating various signaling pathways and promoting the differentiation of T-helper (Th) 1 and Th17 cells; however, it is rarely reported in rheumatoid arthritis (RA). This study aimed to assess the correlation of MALT1 with Th1 and Th17 cells and evaluate its potential as a biomarker for evaluating disease activity and treatment outcomes in RA patients. METHODS: This study enrolled 139 RA patients and 45 health controls (HCs); then, blood MALT1, Th1, and Th17 cells were determined. For RA patients only, blood MALT1 at week (W) 6 and W12 after treatment was also detected. Additionally, clinical response and remission of RA patients were assessed at W12. RESULTS: MALT1 (p < 0.001), Th1 (p = 0.011), and Th17 (p < 0.001) cells were all increased in RA patients than HCs; meanwhile, increased MALT1 was associated with elevated Th1 (p = 0.003) and Th17 (p < 0.001) cells in RA patients. Besides, MALT1, Th1, and Th17 cells were positively correlated with parts of disease activity indexes in RA patients (all p < 0.050). In addition, MALT1 was gradually declined from W0 to W12 (p < 0.001) in RA patients. Specifically, MALT1 at W6 and W12 was lower in response patients than no response patients (both p < 0.010), also in remission patients than no remission patients (both p < 0.050). CONCLUSION: MALT1, Th1, and Th17 cells are dysregulated, inter-correlated, and correlated with disease activity in RA patients; meanwhile, the decline of MALT1 expression can partly reflect RA treatment response and remission.
33620516 The accuracy of administrative health data for identifying patients with rheumatoid arthri 2021 Apr The use of administrative health datasets is increasingly important for research on disease trends and outcome. The Western Australian (WA) Rheumatic Disease Epidemiological Registry contains longitudinal health data for over 10,000 patients with rheumatoid arthritis (RA). Accurate coding for RA is essential to the validity of this dataset. Investigate the diagnostic accuracy of International Classification of Diseases (ICD)-based discharge codes for RA at WA's largest tertiary hospital. Medical records for a sample of randomly selected patients with ICD-10 codes (M05.00-M06.99) in the hospital discharge database between 2008 and 2020 were retrospectively reviewed. Rheumatologist-reported diagnoses and ACR/EULAR classification criteria were used as reference standards to determine accuracy measures. Medical chart review was completed for 87 patients (mean (± SD) age 64.7 ± 17.2 years), 67.8% female). A total of 80 (91.9%) patients had specialist confirmed RA diagnosis, while seven patients (8%) had alternate clinical diagnoses. Among 87 patients, 69 patients (79.3%) were fulfilled ACR/EULAR classification criteria. The agreement between the reference standards was moderate (Kappa 0.41). Based on rheumatologist-reported diagnoses and ACR/EULAR classification criteria, primary diagnostic codes for RA alone had a sensitivity of (90% vs 89.8%), and PPV (90.9% vs 63.6%), respectively. A combination of a diagnostic RA code with biologic infusion codes in two or more codes increased the PPV to 97.9%. Hospital discharge diagnostic codes in WA identify RA patients with a high degree of accuracy. Combining a primary diagnostic code for RA with biological infusion codes can further increase the PPV.
34006673 [Recent Perspectives for Targeted Therapies]. 2021 May It is well known that targeted therapies have led to a paradigm shift in the treatment of autoimmune/inflammatory diseases such as rheumatoid arthritis. Biologics use intravenous or subcutaneous injection because of their size (90-150 kDa) and target multiple cytokines such as TNF and IL-6, as well as cell surface functioning molecules such as CD28 and CD20. Orally available low-molecular weight products target intracellular signaling molecules, including JAK, BTK, and S1P1. Biologics and JAK inhibitors are novel and have new modes of action that effectively close the unmet medical needs of multiple autoimmune/inflammatory diseases. Furthermore, such targeted therapies have the potential to bring about a paradigm shift in the treatment of immune/inflammatory diseases of the central nervous system.
34360655 Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Acti 2021 Jul 23 Low-dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, "Ozone peroxides" are able to replace H(2)O(2) in its specific function of regulation, restore redox signaling, and improve the antioxidant capacity. Two different mechanisms have to be understood. Firstly, there is the direct mechanism, used in topical treatments, mostly via radical reactions. In systemic treatments, the indirect, ionic mechanism is to be discussed: "ozone peroxide" will be directly reduced by the glutathione system, informing the nuclear factors to start the regulation. The GSH/GSSG balance outlines the ozone dose and concentration limiting factor. Antioxidants are regulated, and in the case of inflammatory diseases up-regulated; cytokines are modulated, here downregulated. Rheumatoid arthritis RA as a model for chronic inflammation: RA, in preclinical and clinical trials, reflects the pharmacology of ozone in a typical manner: SOD (superoxide dismutase), CAT (catalase) and finally GSH (reduced glutathione) increase, followed by a significant reduction of oxidative stress. Inflammatory cytokines are downregulated. Accordingly, the clinical status improves. The pharmacological background investigated in a remarkable number of cell experiments, preclinical and clinical trials is well documented and published in internationally peer reviewed journals. This should encourage clinicians to set up clinical trials with chronic inflammatory diseases integrating medical ozone as a complement.
33517445 Post-GWAS functional studies reveal an RA-associated CD40-induced NF-kB signal transductio 2021 May 28 Currently, it remains difficult to identify which single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are functional and how various functional SNPs (fSNPs) interact and contribute to disease susceptibility. GWAS have identified a CD40 locus that is associated with rheumatoid arthritis (RA). We previously used two techniques developed in our laboratory, single nucleotide polymorphism-next-generation sequencing (SNP-seq) and flanking restriction enhanced DNA pulldown-mass spectrometry (FREP-MS), to determine that the RA risk gene RBPJ regulates CD40 expression via a fSNP at the RA-associated CD40 locus. In the present work, by applying the same approach, we report the identification of six proteins that regulate RBPJ expression via binding to two fSNPs on the RA-associated RBPJ locus. Using these findings, together with the published data, we constructed an RA-associated signal transduction and transcriptional regulation network (STTRN) that functionally connects multiple RA-associated risk genes via transcriptional regulation networks (TRNs) linked by CD40-induced nuclear factor kappa B (NF-kB) signaling. Remarkably, this STTRN provides insight into the potential mechanism of action for the histone deacetylase inhibitor givinostat, an approved therapy for systemic juvenile idiopathic arthritis. Thus, the generation of disease-associated STTRNs based on post-GWAS functional studies is demonstrated as a novel and effective approach to apply GWAS for mechanistic studies and target identification.
33963659 Comparing cost of intravenous infusion and subcutaneous biologics in COVID-19 pandemic car 2021 Sep OBJECTIVES: One important group of people at higher risk from the SARS-CoV-2(COVID-19) pandemic are those with autoimmune conditions including rheumatoid arthritis/inflammatory bowel disease. To minimise infection risk, many people have been switched from intravenous to subcutaneous biologics including biosimilars. DESIGN: The survey was designed to understand comparative economic issues related to the intravenous infusion vs subcutaneous biologic administration routes for infliximab. The survey focused on direct cost drivers/indirect cost drivers. Acquisition costs of medicines were not included due to data not being available publicly. Wider policy implications linked to the pandemic were also explored. SETTING/PARTICIPANTS: Semistructured single telephone interviews were carried out with twenty key stakeholders across the National Health Service(NHS) from 35 clinical/42 pharmacy/28 commissioning roles. The interviews were undertaken virtually during April 2020. From interview (n = 20) results, a simple cost analysis was developed plus a qualitative analysis of reports on wider policy/patient impacts. RESULTS: Key findings included evidence of significant variation in local infusion tariffs UK wide, with interviewees reporting that not all actual costs incurred are captured in published tariff costs. A cost analysis showed administration costs 50% lower in the subcutaneous compared to infusion routes, with most patients administering subcutaneous medicines themselves. Other indirect benefits to this route included less pressure on infusion unit waiting times/reduced risk of COVID-19 infection plus reduced patient 'out of pocket' costs. However, this was to some extent offset by increased pressure on home-care and community/primary care services. CONCLUSIONS: Switching from infusion to subcutaneous routes is currently driven by the COVID-19 pandemic in many services. A case for biologics (infusion vs subcutaneous) must be made on accurate real-world economic analysis. In an analysis of direct/indirect costs, excluding medicine acquisition costs, subcutaneous administration appears to be the more cost saving option for many patients even without the benefit of industry funded home-care. What's known One important group of people at high risk in COVID-19 pandemic are those with autoimmune conditions, including those with rheumatoid arthritis and inflammatory bowel disease. Depending on the complexity of their condition, some of the patients in this group may be receiving intravenous biologic infusion therapy which under normal circumstances is administered within a hospital or day hospital setting. The National Institute for Health and Care Excellence has published new guidance to ensure that patients having intravenous treatment are assessed for possible switching to the same treatment in subcutaneous form. What's new A cost analysis showed that administration costs for subcutananous routes are 50% lower than for infusion routes, with most patients administering subcutaneous medicines themselves. Other indirect benefits to this route included less pressure on infusion unit waiting times and reduced risk of COVID-19 infection, along with reduced patient costs. Cost savings were partly offset by increased pressure on home-care and community/primary care services.
34740842 B cell depletion treatment decreases Th17 cells in patients with rheumatoid arthritis. 2021 Dec INTRODUCTION: We aimed to evaluate for any possible effects of treatment with rituximab (RTX) on the peripheral Th17 and Treg subpopulations in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: We analyzed 16 patients with RA initiating RTX treatment, 11 patients with RA initiating abatacept treatment, 11 patients with RA treated with other medications, 8 patients with other autoimmune rheumatic diseases initiating RTX, and 14 healthy volunteers. Th17 cells (CD4(+)IL23R(+)IL17A(+)) and Treg cells (CD4(+)CD25(hi)FoxP3(+)) were evaluated flow-cytometrically. RESULTS: Th17 cells from patients treated with RTX decreased significantly at weeks 8 and 16 (mean ± SEΜ: 3.01% ± 0.54℅ CD4(+) cells at week 0 vs. 1.53% ± 0.24℅ at week 8 vs 1.10% ± 0.20℅ at week 16, p = 0.0004). Reductions of Th17 cells were evident in clinical responders (DAS28 score ≤ 3.2), ACPA (+) and RF (-) patients; circulating Tregs remained stable. Th17 and Tregs were not affected by ABA treatment or by changes in disease activity. Tregs, but not Th17 cells, decreased following treatment with RTX in patients with other autoimmune diseases (0.75% ± 0.16% at week 0 vs. 0.43% ± 0.16% at week 8, p = 0.033). CONCLUSION: RTX-induced B cell depletion results in a significant reduction of circulating Th17 cell percentages, whereas it has no effect on Tregs of patients with RA. This reduction of Th17 cells was evident particularly in responders to RTX treatment, ACPA+ and RF (-) patients with RA.
33527195 Systemic pharmacological investigation of the Feng Shi Gu Tong capsule in the treatment of 2021 Jun Feng Shi Gu Tong (FSGT) capsule is a commonly used Chinese Traditional Patent Medicine in clinical practice, which has been proven to be effective for the treatment of active rheumatoid arthritis (RA). However, due to its complex composition, the precise molecular mechanism of the FSGT capsule in the treatment of RA is still indistinct. Therefore, the method of systemic pharmacology was used to obtain candidate compounds through absorption, distribution, metabolism, elimination (ADME) parameters, and supplementation of references. Network construction and analysis were also included to reveal the potential mechanism of FSGT capsule in treating RA. A total of 119 compounds were obtained in FSGT capsule, and a total of 107 compounds with targets were included in the study. These compounds acted on 267 targets in total. In addition, there were 317 targets related to RA disease. All constructed networks included four major networks and four minor networks. In addition, the clusters of RA disease protein-protein interaction (PPI) network and FSGT capsule-RA disease targets network revealed that the biological process involved in these clusters including immune response and apoptosis, etc. The pathways enriched by the direct targets of FSGT capsule acted on RA also highly overlapped with the pathways enriched by the RA PPI network, such as the TNF signaling pathway. Our research has managed to predict and explain the pharmacological effects and the molecular mechanisms of the FSGT capsule in RA, and provided a realistic exploration method for studying the potentially active ingredients of traditional Chinese medicines simultaneously.
34485516 miR-143-3p Inhibits the Differentiation of Osteoclast Induced by Synovial Fibroblast and M 2021 Osteoclast, which mediates overactive bone resorption, is one of the key factors for bone destruction in rheumatoid arthritis (RA). Existing studies have shown that abnormal miR-143-3p expression was observed in both RA patients and arthritis animals, which can participate in osteoclast differentiation, and mitogen-activated protein kinase (MAPK) signaling pathway was closely related to osteoclast differentiation. The primary objective of the current study was to determine the role of miR-143-3p in the progression of osteoclast differentiation and its relationship with MAPK signaling pathways. The results showed that miR-143-3p inhibited osteoclast differentiation and decreased the levels of M-CSF and RANKL during osteoclast differentiation. miR-143-3p inhibited the expression of MAPK signaling proteins, which is ERK1/2 in the early stage and JNK in the later stage of osteoclast differentiation. It was also observed that MAPK inhibitors upregulated miR-143-3p expression in osteoclast differentiation. Taken together, our results suggested that miR-143-3p could inhibit the differentiation of osteoclast, which was related to inhibiting MAPK signaling pathways. This may provide a novel strategy for curing RA.
33772350 Rheumatoid arthritis in Colombia: a clinical profile and prevalence from a national regist 2021 Sep BACKGROUND: There is a need to describe the demographic and clinical characteristics of people diagnosed with rheumatoid arthritis who are attended within the Colombian health system. This characterization allows prioritizing populations with specific risks, programming the use of health services, and planning the costs necessary to guarantee equitable care. OBJECTIVE: To assess the demographic and clinical characteristics of a cohort of patients with rheumatoid arthritis using national data collected by the High-Cost Disease Fund (CAC in Spanish). METHODS: A cross-sectional study from a secondary source. Data was gathered from a national administrative registry. A descriptive analysis was performed on sociodemographic and clinical characteristics. Age-standardized prevalence was estimated at national level and by geographical regions. Remission rates were also estimated for Colombian departments and regions. RESULTS: By 2019, 81,386 patients with rheumatoid arthritis were reported in Colombia. The relation female-male was 5.2:1. The median age was 59 years (IQR: 50-67). Prevalence was higher in people aged 50-69 years. The most frequent comorbidities were high blood pressure (31.15%) and osteoporosis (19.46%). Age-standardized prevalence of rheumatoid arthritis was 0.24 per 100 population (95% CI: 0.23-0.24). In cases with complete information, 57.57% of departments had remission rates up to 30%. CONCLUSION: Rheumatoid arthritis in Colombia was more frequent in females aged ≥50 year. Age-standardized prevalence was lower than reported by other studies performed in Colombia but similar to the estimated internationally for the country. Key Points • More than 80,000 rheumatoid arthritis patients were reported to this national registry in Colombia in 2019, finding an age-standardized prevalence of 0.24 per 100 population. • Hypertension was the most common comorbidity reported in people with rheumatoid arthritis. This finding is similar to the reports by similar studies such as the COMORA. • A major strength of this study is the large sample size since data come from a nationwide registry of people with rheumatoid arthritis, supported by the National Ministry of Health. Additionally, this registry has a rigorous data monitoring process that guarantees the internal validity of data and provides valuable information for decision-making based on local evidence. • Prevalence of rheumatoid arthritis was higher in females between 50 and 65 years. Age-standardized prevalence was lower than previously reported in Colombia, but similar to the world estimations.
33296090 Tripterygium wilfordii: An inspiring resource for rheumatoid arthritis treatment. 2021 May Tripterygium wilfordii Hook F (TwHF)-based therapy is among the most efficient and crucial therapeutics for the treatment of rheumatoid arthritis (RA), which indicates that TwHF is a potential source of novel anti-RA drugs. However, accumulating studies have observed that TwHF-based therapy induces multi-organ toxicity, which prevents the wide use of this herb in clinical practice, although several recent studies have attempted to reduce the toxicity of TwHF. Notably, our research group developed a "Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the Treatment of Rheumatoid Arthritis" (No. T/CACM 1337-2020) approved by the China Association of Chinese Medicine to standardize the clinical application of TwHF-based therapy and thus avoid adverse effects. Although great strides have been made toward the characterization of TwHF-based therapy and revealing its underlying pharmacological and toxicological mechanisms, several crucial gaps in knowledge remain as potential barriers to enhance its therapeutic effects on the premise of safety assurance. This review offers a global view of TwHF, ranging from its chemical constituents, quality control, clinical observations, and underlying pharmacological mechanisms to toxic manifestations and mechanisms. We focus on the important and emerging aspects of this field and highlight the major challenges and strategies for using novel techniques and approaches to gain new insights into unresolved questions. We hope that this review will improve the understanding of TwHF application and draw increasing interdisciplinary attention from clinicians that practice both Chinese and Western medicine, basic researchers, and computer scientists.
34868079 A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis 2021 BACKGROUND: The etiology of rheumatoid arthritis (RA) remains poorly understood. Early and accurate diagnosis still difficult to achieve. Inflammatory related molecules released into the circulation such cytokines and exosome-derived microRNAs (exomiRNAs) could be good candidates for early diagnosis of autoimmune diseases. We sought to discover a serum biomarker panel for the early detection of RA based on exomiRNAs and inflammatory markers. METHODS: A 179 miRNAs-microarray panel was analyzed in a pilot study (4 early RA and 4 controls). Validation of deregulated exomiRNAs was performed in a larger cohort (24 patients with early RA and 24 controls). miRNet software was used to predict exomiRNA gene-targets interactions. Potentially altered pathways were analyzed by Reactome pathway database search. STRING database was used to predict protein-protein interaction networks. Enzyme-linked immunosorbent assay was used to measure serum levels of sTWEAK and sCD163. Signature biomarker candidates were statistical analyzed. RESULTS: We detected 11 differentially expressed exomiRNAs in early RA pilot study. Validation analysis revealed that 6/11 exomiRNAs showed strong agreement with the pilot microarray data (exomiR-144-3p, -25-3p, -15a-5p, -451a, -107 and -185-5p). sTWEAK and sCD163 biomarkers were significantly elevated in the serum of patients with early RA. Receiver operating characteristic (ROC) analysis showed that the best panel to diagnose early RA contained exomiR-451a, exomiR-25-3p and sTWEAK, and could correctly classify 95.6% of patients, with an area under the ROC curve of 0.983 and with 100% specificity and 85.7% sensitivity. The YWHAB gene was identified as a common target of the putative miRNA-regulated pathways. CONCLUSION: A novel serum biomarker panel composed of exomiR-451a, exomiR-25-3p and serum levels of sTWEAK may have use in the early clinical diagnosis of RA. A new predicted exomiRNA-target gene YHWAB has been identified and may have a relevant role in the development of RA.
34721412 Molecular Changes in the Adipose Tissue Induced by Rheumatoid Arthritis: Effects of Diseas 2021 Disease severity, progression and response to therapy might be worse in obese rheumatoid arthritis (RA) patients, but paradoxically, obesity also might protect from radiographic joint damage. Thus, the intricate relationship between obesity and RA needs urgent clarification. The aim of this study was to assess the influence of obesity on the onset and development of RA and to determine whether arthritis could modify the adipose tissue biology and whether conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) can modulate these alterations. Two strategies were followed: (1) clinical profiling of two cohorts of RA: non-obese and obese patients; and (2) mechanistic studies carried out in both a collagen-induced arthritis (CIA) in an obese mouse model and 3T3-L1 adipocytes treated with cDMARDs (leflunomide, methotrexate, and hydroxychloroquine). In our cohort of RA patients with low-moderate disease activity, the presence of obesity was not related to a higher activity of the disease; actually, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) was reduced in the obese RA patients. However, the induction of arthritis promoted transcriptomic changes in the adipose tissue under obesity condition in the obese CIA model. Treatment with hydroxychloroquine reduced weight and insulin resistance, accompanied by beneficial metabolic effects in the adipose tissue. These molecular changes in adipose tissue were also observed after methotrexate administration. In sum, arthritis might affect directly the inflammatory burden and metabolic alterations associated with obesity in adipose tissue. Clinicians should be cautious measuring the activity of the disease in obesity and managing the best therapeutic options for the metabolic comorbidities of these patients, where the combination of hydroxychloroquine and methotrexate should be considered to improve adipose tissue dysfunction in obese RA.
34372936 The efficacy of low dose short-term prednisone therapy for remission induction in newly di 2021 Aug 9 BACKGROUND: The ACR/EULAR recommendations endorse the use of glucocorticoids (GCs) for rheumatoid arthritis (RA) patients' flares and as a bridge to a DMARD. However, the recommendation of low dose short-term monotherapy with (GCs) remains open to the discretion of the clinician. The aim of this study was to assess whether a short-term use of low dose prednisone monotherapy was effective in inducing remission in newly diagnosed RA patients. METHODS: A retrospective analysis of patients newly diagnosed with RA at a Community Health Center in North Dakota was performed based on the ACR/EULAR RA classification criteria. Demographic and clinical data were abstracted from patients' medical charts. Patients treated with (< 10 mg/day) of prednisone up to 6 months were included. Response to prednisone was analyzed according to pre- and post-treatment DAS28-ESR score and EULAR response criteria. RESULTS: Data on 201 patients were analyzed. The mean prednisone dose was 8 mg/day (range: 5-10; SD = 1.2) and the mean treatment duration was 42.2 days (12-177; 16.9). Disease severity significantly improved from baseline to follow-up for: tender joint count (8.6 ± 4.8 vs. 1.5 ± 3.3; P < 0.001), swollen joint count (6.2 ± 5.0 vs. 1.4 ± 3.0; P < 0.001), and visual analog pain score (4.8 ± 2.6 vs. 2.1 ± 2.5; P < 0.001). DAS28-ESR disease severity significantly improved from baseline to follow-up: (5.1 ± 1.2 vs. 2.7 ± 1.3; P < 0.001). Per EULAR response criteria, 69.7% of patients showed good response to treatment and 20.4% showed moderate response. 54.2% of patients reached remission. CONCLUSION: Short-term use of low dose prednisone monotherapy induced disease remission and improved clinical severity of RA in the majority of newly diagnosed patients.
33933432 Erythrocyte reduced/oxidized glutathione and serum thiol/disulfide homeostasis in patients 2021 Aug BACKGROUND: Chronic inflammation and oxidative stress are the most known mechanisms in Rheumatoid Arthritis (RA) pathophysiology, which is still not fully elucidated. In this study, we evaluated oxidative status by determining intracellular reduced/oxidized glutathione (GSH/GSSG) homeostasis and serum thiol/disulfide (SH/SS) homeostasis in RA patients. METHODS: A total of 152 RA patient and 89 healthy controls were included in the study. RA patients were subdivided according to disease activity score-28 (DAS-28) as active RA and remission RA. Intracellular GSH/GSSG and serum SH/SS homeostasis parameters were analyzed. RESULTS: Median (1st-3rd quartile values) SS/SH and GSSG/GSH percent ratio levels were significantly higher in RA patients (6.94 (6.02-8.54) and 69.8 (44.05-85.29); respectively) compared to controls (4.62 (4.15-5.46) and 34.9 (22.43-62.2); respectively) (p < 0.05 for all). SS/SH and GSSG/GSH percent ratio levels were significantly higher in active RA patients when compared to remission RA patients and controls (p < 0.05 for all). SS/SH and GSSG/GSH percent ratios were significantly increased in remission RA group compared to controls (p < 0.05 for all). DAS28 scores were positively correlated with SS/SH and GSSG/GSH percent ratios (rho = 0.259 and 0.296; respectively). CONCLUSIONS: These findings suggest that active intracellular and extracellular thiol group oxidation process might play a role in RA pathogenesis and further work in these areas may be warranted to show potential value of evaluating intracellular GSSG/GSH and serum SH/SS balances together in disease monitoring.
33040226 Fatigue is cross-sectionally not associated with objective assessments of inflammation, bu 2021 May OBJECTIVE: The associations between fatigue and disease activity in patients with rheumatoid arthritis (RA) have not been defined. The present objectives were to explore in RA patients the cross-sectional and longitudinal relation of fatigue with subjective as well as objective assessments of disease activity. METHODS: RA patients were consecutively included when initiating biologic disease-modifying anti-rheumatic drugs (DMARDs) and assessed at baseline, 1, 2, 3, 6, and 12 months with investigation of fatigue, patient-reported outcome measures (PROMs; joint pain and patient's global disease activity, MHAQ, pain catastrophizing, Mental Health score), clinical examinations (examiner's global disease activity, 28 tender and swollen joint counts), and laboratory variables (ESR, CRP, calprotectin). Ultrasound examinations (semi-quantitative scoring (0-3)) with grey scale and power Doppler were performed of 36 joints and 4 tendons. Statistics included one-way analysis of variance, Pearson's correlations, and multiple linear and logistic regression analysis. RESULTS: A total of 208 RA patients (mean (SD) age 53.2 (13.2) years, disease duration 9.8 (8.5) years) were included. Fatigue levels diminished during follow-up (mean (SD) baseline/12 months; 4.8 (2.8)/3.0 (2.5) (p < 0.001)). Substantial correlations were cross-sectionally found between fatigue and PROMs (median (IQR) r=0.61 (0.52-0.71)) but not with the objective inflammatory assessments. During follow-up, baseline fatigue was associated with PROMs (p < 0.001) but not with objective inflammatory assessments. However, change of fatigue was associated with change in all variables. Higher baseline fatigue levels were associated with lower clinical composite score remission rates. CONCLUSION: Fatigue was cross-sectionally associated to subjective but not to objective disease assessments. However, change of fatigue during treatment was associated to all assessments of disease activity. TRIAL REGISTRATION NUMBER: Anzctr.org.au identifier ACTRN12610000284066, Norwegian Regional Committee for Medical and Health Research Ethics South East reference number 2009/1254 Key Points • In this longitudinal study of patients with established RA, fatigue was associated with patient reported outcome measures at each visit, but not with objective assessments of inflammation including calprotectin and comprehensive ultrasound examinations. • Changes in fatigue during biological treatment were associated with changes in patient reported outcome measures, clinical, laboratory and ultrasound assessments. • Baseline fatigue was associated with all patient reported outcome measures, but not objective assessments of inflammation at all the prospective visits. • Higher baseline fatigue levels were associated with lower remission rates as assessed by clinical composite scores.
34076348 Systematic review and meta-analysis on prevalence of metabolic syndrome in psoriatic arthr 2021 Sep BACKGROUND: Psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis (PsO) are associated with systemic inflammation and increased cardiovascular mortality and morbidity. Metabolic syndrome (MetS) is associated with systemic inflammation, and conditions associated with MetS, such as obesity, are associated with difficulty in attaining minimal disease activity (MDA) in individuals with inflammatory arthritis. This systematic review aims to determine whether there is an increased prevalence of MetS in PsA populations compared with PsO and RA populations. METHODS: A systematic review was conducted to assess the prevalence of MetS in PsA, PsO, and RA populations following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The quality of the studies reviewed was assessed using the Joanna Briggs Institute Checklist for Prevalence Studies. RESULTS: The pooled prevalence of MetS in PsA populations was 0.46 ± 0.06 (95% CI 0.40-0.51). In comparison, the prevalence of MetS in PsO and RA populations was 0.34 ± 0.03 (95% CI 0.32-0.37) and 0.31 ± 0.04 (95% CI 0.27-0.35), respectively. Patients with PsA were 1.62 ± 0.036 (95% CI 1.50-1.74) and 1.66 ± 0.038 (95% CI 1.54-1.79) times more likely to have MetS compared with PsO and RA populations. CONCLUSION: The prevalence of MetS is significantly increased in PsA populations compared with PsO and RA populations. Further studies should be performed using a standardized definition of MetS in PsA, RA, and PsO populations to determine whether addressing the metabolic components in MetS offers any therapeutic benefits and in terms of attaining MDA and improving cardiovascular health.
33950227 How important is JAK1 selectivity? 2021 May 5 CME: This supplement is CME Accredited. To receive a CME certificate of participation, you should:  Read all the papers in the supplement Register or log in at www.paradigmmc.com/962 to complete and submit the post activity assessment. You must answer 70% of the questions correctly to earn credit. You will have unlimited opportunities to successfully complete the assessment. You will receive a maximum of 7.0 AMA PRA Category 1 Credits(TM) upon successful completion of the assessment.
34006152 Methotrexate and cardiovascular risk in rheumatic diseases:A comprehensive review. 2021 Sep Introduction: Management of inflammatory rheumatic diseases has evolved based on improved treatment strategies and better management of comorbidities, specifically cardiovascular risk. Methotrexate is one of the first-line treatments in the management of inflammatory rheumatic diseases, but its cardiovascular effects are poorly understood. The purpose of this review is to assess the cardiovascular impact of methotrexate in inflammatory rheumatic disease.Areas covered: Current knowledge about the mechanism of action of methotrexate on cardiovascular tissue is presented. A review of the literature in the Medline, Cochrane and Embase databases was performed. Current data about the cardiovascular effects of methotrexate in rheumatoid arthritis, psoriatic arthritis, and psoriasis are presented.Expert opinion: Mechanism of action of methotrexate is based on the antagonism of purines. It reduces systemic inflammation and oxidative stress and improves the major cardiovascular risk factors. Methotrexate improves cardiovascular risk in rheumatoid arthritis, psoriasis and psoriatic arthritis, but the mechanisms involved are partially identified. Data are controversial regarding its effects on endothelial function and atherosclerosis. Conversely, in the general population and in patients with HIV infection, methotrexate does not modify cardiovascular outcomes. Thus, methotrexate only improves cardiovascular risk by reducing systemic inflammation, and should not be used to prevent cardiovascular events.
35069529 Overload of the Temporomandibular Joints Accumulates γδ T Cells in a Mouse Model of Rheu 2021 Recently, it has been reported that γδ T cells are associated with the pathology of rheumatoid arthritis (RA). However, there are many uncertainties about their relationship. In this study, we investigated the morphological and histological properties of peripheral as well as temporomandibular joints (TMJ) in a mouse model of rheumatoid arthritis with and without exposure to mechanical strain on the TMJ. Collagen antibody-induced arthritis (CAIA) was induced by administering collagen type II antibody and lipopolysaccharide to male DBA/1JNCrlj mice at 9-12 weeks of age, and mechanical stress (MS) was applied to the mandibular condyle. After 14 days, 3D morphological evaluation by micro-CT, histological staining (Hematoxylin Eosin, Safranin O, and Tartrate-Resistant Acid Phosphatase staining), and immunohistochemical staining (ADAMTS-5 antibody, CD3 antibody, CD45 antibody, RORγt antibody, γδ T cell receptor antibody) were performed. The lower jawbone was collected. The mandibular condyle showed a rough change in the surface of the mandibular condyle based on three-dimensional analysis by micro-CT imaging. Histological examination revealed bone and cartilage destruction, such as a decrease in chondrocyte layer width and an increase in the number of osteoclasts in the mandibular condyle. Then, immune-histological staining revealed accumulation of T and γδ T cells in the subchondral bone. The temporomandibular joint is less sensitive to the onset of RA, but it has been suggested that it is exacerbated by mechanical stimulation. Additionally, the involvement of γδ T cells was suggested as the etiology of rheumatoid arthritis.