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ID PMID Title PublicationDate abstract
33878447 Phytochemical add-on therapy to DMARDs therapy in rheumatoid arthritis: In vitro and in vi 2021 Jul The use of biologically active compounds derived from plants i.e. phytochemicals, have been known for ages for their pharmacological activities in the treatment of autoimmune disorders like rheumatoid arthritis (RA). Besides enormous scientific evidence, the therapeutic potential of phytochemicals is often undervalued. The treatment in RA involves the use of synthetic and biological disease modifying anti-rheumatic drugs (DMARDs). However, the long-term treatment in RA is associated with the risk of gastrointestinal, liver, pulmonary and renal toxicities and serious infections including latent tuberculosis, pneumococcus influenza, herpes zoster and hepatitis. These adverse effects sometimes lead to discontinuation of the therapy. A relatively new vision based on the combination of DMARDs with phytochemicals exhibiting anti-inflammatory, anti-arthritic, anti-oxidant, hepatoprotective and nephroprotective properties for the treatment of RA has achieved substantial importance in the last decade. From this perspective, the present review focuses on the combination of DMARDs (primarily MTX) with phytochemicals that have shown synergistic therapeutic effects while decreasing the toxic repercussions of current RA therapy. The review covers recent evidences of such combination studies that have shown promising results both in experimental arthritic models and clinical arthritis. Few of the combinations including resveratrol, sinomenine, coenzyme Q10 exhibited considerable interest because of their efficacy as an adjuvant to the MTX/standard DMARDs therapy in clinical trials. Besides giving an overview of such combination studies the review also critically discusses the limitations with the use of phytochemicals (e.g. solubility, permeability and bioavailability) compromising their clinical application. Additionally, it stresses upon the need of novel delivery systems and pharmaceutical technologies to increase the therapeutic efficacy of the combination therapy. Overall, the review unveils the potential of phytochemicals in combination with DMARDs with increased tolerability and superior efficacy in further refining the future of the RA therapy.
33076814 Can Cytokines be used as an Activation Marker in Rheumatoid Arthritis? 2021 AIMS: The etiopathogenesis of Rheumatoid Arthritis (RA) is not clearly understood. However, the role of the cytokines play an important part in this mechanism. We aimed to bring a new approach to the concept of 'remission' in patients with RA. BACKGROUND: RA is a chronic, autoimmune, inflammatory disease that involves small joints in the form of symmetrical polyarthritis and progresses with exacerbations and remissions. Pain, swelling, tenderness and morning stiffness are typical of the joints involved. Although it is approached as primary joint disease, a wide variety of extra-articular involvements may also occur. It is an interesting pathophysiological process, the exact cause of which is still unknown, with many environmental, genetic and potentially undiscovered possible factors in a chaotic manner. OBJECTIVE: In this cross-sectional study, sedimentation rate (ESR), C- Reactive protein (CRP), Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and IL-10 were measured in three groups which were healthy volunteers, patients with RA in the active period, and patients with RA in remission. Disease activity score-28 (DAS-28) was calculated in active RA and RA in remission. METHODS: This study included 20 healthy volunteers, 20 remission patients with RA and 20 active RA patients. Venous blood samples were collected from patients in both healthy and RA groups. RESULTS: RA group consisted 43 (71.6%) female and 17 (28.4%) male. Control group consisted 11 (55%) female and 9 (45%) male. TNF-R was significantly high only in the active group according to the healthy group (p=0.002). IL-10 was significantly high in active RA, according to RA in remission (p=0.03). DAS-28 was significantly high in active RA, according to RA in remission (p=0.001). In the active RA group, ESR and TNF-R had a positive correlation (r:0.442; p=0.048). In the active RA group, there was also a positive correlation between TNF-R and CRP (r:0.621; p=0,003). Both healthy and active RA group had significant positive correlation between ESR and CRP (r: 0.481; p=0.032 and r: 0,697; p=0,001 respectively). CONCLUSION: TNF-R can be the main pathophysiological factor and a marker showing activation. TNF-R can be very important in revealing the effect of TNF on the disease and the value of this effect in the treatment and ensuring the follow-up of the disease with CRP instead of ESR in activation.
33512428 Associations between serum antibodies to periodontal pathogens and preclinical phases of r 2021 Oct 2 OBJECTIVES: To examine whether serum antibodies against selected periodontal pathogens are associated with early symptoms of RA development in healthy individuals at risk of developing the disease. METHODS: Within an ongoing study cohort of first-degree relatives of patients with RA (RA-FDRs), we selected four groups corresponding to specific preclinical phases of RA development (n = 201). (i) RA-FDR controls without signs and symptoms of arthritis nor RA-related autoimmunity (n = 51); (ii) RA-FDRs with RA-related autoimmunity (n = 51); (iii) RA-FDRs with inflammatory arthralgias without clinical arthritis (n = 51); and (iv) RA-FDRs who have presented at least one swollen joint ('unclassified arthritis') (n = 48). Groups were matched for smoking, age, sex and shared epitope status. The primary outcome was IgG serum levels against five selected periodontal pathogens and one commensal oral species assessed using validated-in-house ELISA assays. Associations between IgG measurements and preclinical phases of RA development were examined using Kruskal-Wallis or Mann-Whitney tests (α = 0.05). RESULTS: None of the IgGs directed against individual periodontal pathogens significantly differed between the four groups of RA-FDRs. Further analyses of cumulated IgG levels into bacterial clusters representative of periodontal infections revealed significantly higher IgG titres against periodontopathogens in anti-citrullinated protein antibodies (ACPA)-positive RA-FDRs (P = 0.015). Current smoking displayed a marked trend towards reduced IgG titres against periodontopathogens. CONCLUSION: Our results do not suggest an association between serum IgG titres against individual periodontal pathogens and specific preclinical phases of RA development. However, associations between cumulative IgG titres against periodontopathogens and the presence of ACPAs suggest a synergistic contribution of periodontopathogens to ACPA development.
34229715 Radiological and clinical outcomes of balloon kyphoplasty for osteoporotic vertebral compr 2021 Jul 6 BACKGROUND: This study was conducted to investigate the outcomes and complications of balloon kyphoplasty (KP) for the treatment of osteoporotic vertebral compression fracture (OVCF) in patients with rheumatoid arthritis (RA) and compare its radiological and clinical effects with OVCF patients without RA. METHODS: Ninety-eight patients in the RA group with 158 fractured vertebrae and 114 patients in the control group with 150 vertebrae were involved in this study. Changes in compression rate, local kyphotic angle, visual analog scale (VAS) and Oswestry disability index (ODI) scores, conditions of bone cement leakage, refracture of the operated vertebrae, and new adjacent vertebral fractures were examined after KP. In addition, patients in the RA group were divided into different groups according to the value of erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and whether they were glucocorticoid users or not to evaluate their influence on the outcomes of KP. RESULTS: KP procedure significantly improved the compression rate, local kyphotic angle, and VAS and ODI scores in both RA and control groups (p<0.05). Changes in compression rate and local kyphotic angle in the RA group were significantly larger than that in the control group (p<0.05), and patients with RA suffered more new adjacent vertebral fractures after KP. The outcomes and complications of KP from different ESR or CRP groups did not show significant differences. The incidence of cement leakage in RA patients with glucocorticoid use was significantly higher than those who did not take glucocorticoids. In addition, RA patients with glucocorticoid use suffered more intradiscal leakage and new adjacent vertebral fractures. CONCLUSIONS: OVCF patients with RA obtained more improvement in compression rate and local kyphotic angle after KP when compared to those without RA, but they suffered more new adjacent vertebral fractures. Intradiscal leakage and new adjacent vertebral fractures occurred more in RA patients with glucocorticoid use. TRIAL REGISTRATION: Retrospectively registered.
34521481 Chronic inflammation-induced senescence impairs immunomodulatory properties of synovial fl 2021 Sep 14 BACKGROUND: Although the immunomodulatory properties of mesenchymal stem cells (MSCs) have been highlighted as a new therapy for autoimmune diseases, including rheumatoid arthritis (RA), the disease-specific characteristics of MSCs derived from elderly RA patients are not well understood. METHODS: We established MSCs derived from synovial fluid (SF) from age-matched early (average duration of the disease: 1.7 years) and long-standing (average duration of the disease: 13.8 years) RA patients (E-/L-SF-MSCs) and then analyzed the MSC characteristics such as stemness, proliferation, cellular senescence, in vitro differentiation, and in vivo immunomodulatory properties. RESULTS: The presence of MSC populations in the SF from RA patients was identified. We found that L-SF-MSCs exhibited impaired proliferation, intensified cellular senescence, reduced immunomodulatory properties, and attenuated anti-arthritic capacity in an RA animal model. In particular, E-SF-MSCs demonstrated cellular senescence progression and attenuated immunomodulatory properties similar to those of L-SF-MSC in an RA joint-mimetic milieu due to hypoxia and pro-inflammatory cytokine exposure. Due to a long-term exposure to the chronic inflammatory milieu, cellular senescence, attenuated immunomodulatory properties, and the loss of anti-arthritic potentials were more often identified in SF-MSCs in a long-term RA than early RA. CONCLUSION: We conclude that a chronic RA inflammatory milieu affects the MSC potential. Therefore, this work addresses the importance of understanding MSC characteristics during disease states prior to their application in patients.
33568387 Modern treatment approach results in low disease activity in 90% of pregnant rheumatoid ar 2021 Jul OBJECTIVES: In patients with rheumatoid arthritis (RA), high disease activity impairs fertility outcomes and increases the risk of adverse pregnancy outcomes. The aim of this study was to determine the feasibility of a modern treatment approach, including treat-to-target (T2T) and the prescription of tumour necrosis factor (TNF) inhibitors, in patients with RA with a wish to conceive or who are pregnant. METHODS: Patients were derived from the Preconception Counseling in Active RA (PreCARA) cohort. Patients with a wish to conceive or who are pregnant were treated according to a modified T2T approach, in which the obvious restrictions of pregnancy were taken into account. Results of the PreCARA study were compared with results of the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study, a historic reference cohort on RA during pregnancy. Patients in the PARA cohort were treated according to the standards of that time (2002-2010). Differences in disease activity over time between the two cohorts were tested using a linear mixed model. RESULTS: 309 patients with RA were included in the PreCARA study, 188 children were born. 47.3% of the patients used a TNF inhibitor at any time during pregnancy. Mean disease activity over time in the PreCARA cohort was lower than in the reference cohort (p<0.001). In the PreCARA cohort, 75.4% of the patients were in low disease activity (LDA) or remission before pregnancy increasing to 90.4% in the third trimester, whereas in the PARA cohort, these percentages were 33.2% and 47.3%, respectively. CONCLUSIONS: This first study on a modern treatment approach in pregnant patients with RA shows that LDA and remission are an attainable goal during pregnancy, with 90.4% of patients achieving this in the third trimester.
34651581 Fibroblast pathology in inflammatory diseases. 2021 Oct 15 Fibroblasts are important cells for the support of homeostatic tissue function. In inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease, fibroblasts take on different roles (a) as inflammatory cells themselves and (b) in recruiting leukocytes, driving angiogenesis, and enabling chronic inflammation in tissues. Recent advances in single-cell profiling techniques have transformed the ability to examine fibroblast states and populations in inflamed tissues, providing evidence of previously underappreciated heterogeneity and disease-associated fibroblast populations. These studies challenge the preconceived notion that fibroblasts are homogeneous and provide new insights into the role of fibroblasts in inflammatory pathology. In addition, new molecular insights into the mechanisms of fibroblast activation reveal powerful cell-intrinsic amplification loops that synergize with primary fibroblast stimuli to result in striking responses. In this Review, we focus on recent developments in our understanding of fibroblast heterogeneity and fibroblast pathology across tissues and diseases in rheumatoid arthritis and inflammatory bowel diseases. We highlight new approaches to, and applications of, single-cell profiling techniques and what they teach us about fibroblast biology. Finally, we address how these insights could lead to the development of novel therapeutic approaches to targeting fibroblasts in disease.
32964675 Obesity-Related Traits and the Development of Rheumatoid Arthritis: Evidence From Genetic 2021 Feb OBJECTIVE: To investigate the association between obesity-related traits and risk of rheumatoid arthritis (RA). METHODS: We conducted genetic correlation analysis and a 2-sample Mendelian randomization (MR) study, using genome-wide genetic data based on >850,000 individuals of European ancestry. Summary statistics were collected from the largest genome-wide association study conducted to date for body mass index (BMI; n = 806,810), waist-to-hip ratio (WHR; n = 697,734), WHR adjusted for BMI (WHRadjBMI; n = 694,649), and RA (n(case) = 14,361, n(control) = 43,923). We conducted cross-trait linkage disequilibrium score regression and ρ-HESS analyses to quantify genetic correlation between pairs of traits (causal overlap). For each obesity-related exposure, we utilized independent, genome-wide significant single-nucleotide polymorphisms (P < 5 × 10(-9) ) as instruments to perform MR analysis (causal relationship). We interrogated the causal relationship both in the general population and in a sex-specific manner and calculated odds ratios (ORs) and 95% confidence intervals (95% CIs). Sensitivity analyses were performed to validate MR model assumptions. RESULTS: Despite a negligible overall genetic correlation between the 3 obesity-related traits and RA, we found significant local genetic correlations at several regions on chromosome 6 (positions 28-29M, 30-35M, and 50-52M), highlighting a shared genetic basis. We further observed an increased risk of RA per SD increment (4.8 kg/m(2) ) in genetically predicted BMI (OR 1.22 [95% CI 1.09-1.37]). The effect was consistent across sensitivity analyses and comparable between sexes (OR 1.22 [95% CI 1.04-1.44] in male subjects and 1.19 [95% CI 1.04-1.36] in female subjects). However, we did not find evidence supporting a causal role of either WHR (OR 0.98 [95% CI 0.84-1.14]) or WHRadjBMI (OR 0.90 [95% CI 0.79-1.04]) in RA. CONCLUSION: Genetically predicted BMI significantly increases RA risk. Future studies are needed to understand the biologic mechanisms underlying this link.
34413382 Plasma fibrinogen, D-dimer, and fibrin degradation product as biomarkers of rheumatoid art 2021 Aug 19 This study aimed to assess the association of coagulation-related indicators such as plasma fibrinogen (FIB), D-dimer, and fibrin degradation product (FDP) in rheumatoid arthritis (RA) with the disease activity. Data from 105 RA patients and 102 age- and gender-matched healthy controls were collected in the retrospective study. Disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) was used to divide RA patients into low activity group (DAS28-CRP ≤ 2.7) and active group (DAS28-CRP > 2.7). Receiver operating characteristic (ROC) curve was applied to determine area under the curve (AUC). The association between plasma FIB, D-dimer, and FDP and DAS28-CRP was evaluated by spearman correlation. Logistical regression analysis was used to identify the independent variables associated with RA disease activity. RA patients showed higher levels of plasma FIB, D-dimer, and FDP than the controls (P < 0.01). Plasma FIB, D-dimer, and FDP were also increased in active groups of RA patients than those in inactive groups (P < 0.001). ROC curve analyses revealed that the AUC of D-dimer was higher than erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF), and that of FDP was higher than RF in RA patients. In addition, the optimal cut-off value of plasma FIB, D-dimer, and FDP for RA diagnosis was 286 mg/dL, 470 μg/L, and 1.45 mg/L, respectively. Spearman analysis showed that plasma FIB, D-dimer, and FDP were positively related with DAS28-CRP (P < 0.001) in RA patients. Logistical regression analysis showed that D-dimer (odds ratio 2.862, 95% confidence interval 1.851-5.426, P < 0.001) was an independent variable associated with RA disease activity. FIB, D-dimer, and FDP were increased in RA patients and positively correlated with the disease activity of RA. D-dimer may act as a novel inflammatory indice for indicating disease activity in RA patients.
34899727 Increased Ratio of CD14(++)CD80(+) Cells/CD14(++)CD163(+) Cells in the Infrapatellar Fat P 2021 OBJECTIVES: This study sought to identify the ratio of M1/M2 cells in the infrapatellar fat pads (IFP) and subcutaneous fat tissues (SC) of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. The clinical features of OA and RA patients treated with or without biological disease-modifying anti-rheumatic drugs (bDMARDs) were also assessed. METHODS: IFP and SC were collected from patients with OA and RA who are undergoing total knee arthroplasty (TKA). CD14-positive cells were then isolated from these samples. Flow cytometry was used to determine the number of CD14(++)CD80(+) cells and CD14(++)CD163(+) cells. The expression levels of lipid transcription factors, such as sterol regulatory element-binding protein 1 (SREBP1) and liver X receptor alpha (LXRA), and inflammatory cytokines were also evaluated. RESULTS: Twenty OA patients and 22 RA patients were enrolled in this study. Ten of the RA patients (45.4%) received bDAMRDs before TKA. On average, a fivefold increase in the number of CD14-positive cells and lower expression levels of SREBP1C and LXRA were observed in OA IFP relative to OA SC; however, these results were not obtained from the RA samples. The median ratio of CD14(++)CD80(+) cells/CD14(++)CD163(+) cells of OA IFP was 0.87 (0.76-1.09, interquartile range), which is higher to that of OA SC with a lower ratio (p = 0.05835). CONCLUSIONS: The quantity and quality of CD14-positive cells differed between IFP and SC in arthropathy patients. To our knowledge, this is the first study to characterize the ratio of M1/M2 cells in the IFP and SC of end-stage OA and RA patients. The increased ratio of CD14(++)CD80(+) cells/CD14(++)CD163(+) cells in the IFP from patients with OA and RA treated with bDMARDs indicated that inflammation was localized in the IFP. As adipose tissue-derived innate immune cells were revealed as one of the targets for regulating inflammation, further analysis of these cells in the IFP may reveal new therapeutic strategies for inflammatory joint diseases.
33186593 Traditional and modern management strategies for rheumatoid arthritis. 2021 Jan Rheumatoid arthritis (RA) is a serious disorder of the joints affecting 1 or 2% of the population aged between 20 and 50 years worldwide. RA is the foremost cause of disability in developing and Western populations. It is an autoimmune disease-causing inflammation and pain involving synovial joints. Pro-inflammatory markers, including cytokines, such as interleukin -1 (IL-1), IL-6, IL-7, IL-8, and tumor necrosis factor-α (TNF-α) are involved in RA. RA treatment involves TNF-α blockade, B cell therapy, IL-1 and IL-6 blockade, and angiogenesis inhibition. Synthetic drugs available for the treatment of RA include disease-modifying anti-rheumatic drugs (DMARD), such as cyclophosphamide, sulfasalazine, methotrexate, nonsteroidal anti-inflammatory drugs (NSAIDs), and intramuscular gold. These agents induce adverse hepatorenal effects, hypertension, and gastric ulcers. We found that patients diagnosed with chronic pain, as in RA, and those refractory to contemporary management are most likely to seek traditional medicine. Approximately 60-90% of patients with arthritis use traditional medicines. Therefore, the efficacy and safety of these traditional medicines need to be established. The treatment for RA entails a comprehensive multidisciplinary strategy to reduce pain and inflammation and to restore the activity of joints. The potential medicinal plants exhibiting anti-arthritic and anti-rheumatic pharmacological activity are reviewed here.
32615835 Patient characteristics affecting knowledge of the possibility of surgical reconstruction 2021 May OBJECTIVES: We aimed to investigate patient characteristics affecting their knowledge of surgical reconstruction for rheumatoid hand and wrist deformities, and to investigate such characteristics affecting their hope of receiving hand surgery if patients with rheumatoid arthritis (RA) knew surgical reconstruction options. METHODS: We carried out a questionnaire survey for all patients with RA who came to our outpatient department of rheumatology. Multivariate logistic regression analysis was performed to examine significant characteristics associated with the knowledge of surgical reconstruction and patients' hope of receiving hand surgery. RESULTS: In total, 687 patients were evaluated in this study and 337 (49%) reported knowledge about surgical reconstruction. A multivariate logistic regression analysis showed that patients with good control of disease activity and with long-lasting hand and wrist deformities were significantly associated with having knowledge of surgical reconstruction. Among the 337 patients with knowledge, only 122 (36%) expressed a hope of receiving hand surgery. The statistical analysis showed that younger age and surgical history were significantly associated with the hope of receiving surgery. CONCLUSION: Surgeons and rheumatologists should enlighten patients about the importance of hand surgery to achieve functional remission in this new era of treatment for patients with RA.
34655606 Short-term effect of meteorological factors on the risk of rheumatoid arthritis hospital a 2022 May 1 Rheumatoid arthritis (RA) is an autoimmune disease, mainly characterized by erosional arthritis. The proportion of adults suffering from RA is about 0.5%-1%. There have been reports on the association of rainfall and traffic-related air pollutants with RA hospitalization rates. However, there have been no studies on the association of diurnal temperature range (DTR) and relative humidity (RH) with RA hospitalization rates. This study aimed to examine the short-term association of DTR, RH and other meteorological factors with the hospital admission rate of RA patients, while excluding the interference of PM(2.5), SO(2), NO(2), CO and O(3) atmospheric pollutants. We collected daily RA occupancy rate and meteorological factor data in Hefei city from 2015 to 2018 and used the generalized additive model (GAM) combined with the distributed lag nonlinear model (DLNM) for time series analysis, and further stratified analysis by gender and age. Single-day and cumulative-day risk estimates of RA admissions were expressed as relative risk (RR) and its 95% confidence interval (95% CI). For the cumulative-day lag model, high RH was statistically significant after cumulative lag 0-8 days, and the effect gradually increases. Stratified analysis shows that females seem to be more susceptible to high or extremely high DTR and RH exposure, and extremely high DTR exposure may increase the risk of RA admission in all populations. In conclusion, this study found that high DTR and high RH exposure increased the risk of hospitalization in RA patients and provided clues to the potential association between other meteorological factors and RA.
32613391 Potential role of mitochondria in synoviocytes. 2021 Feb Synoviocytes are located in the synovium lining layer, which is composed of macrophage-like synoviocytes (MLS) and fibroblast-like synoviocytes (FLS) with different characteristics. Mitochondria, which exist in most cells, are two membrane-covered organelles. In addition to providing the necessary ATP for synoviocytes, mitochondria are involved in the regulation of redox homeostasis and the integration of synoviocytes death signals. In recent years, mitochondrial dysfunction has been found in rheumatoid arthritis (RA) and osteoarthritis (OA). Interestingly, recent studies have started uncovering that mitochondria that were previously reported to play a role in chondrocytes or immune cells, but not known to have pronounced roles in synoviocytes, can actually play crucial roles in the regulation of the pathological properties of the synoviocytes. The purpose of this review is to summarize our current understanding of the key role of mitochondria in synoviocytes, including mitochondrial dysfunction in synoviocytes can induce and aggravate inflammatory responses and changes in mitochondrial structure and function with the involvement of multiple cytokines, signal pathway, and hypoxic state of synovial tissue alter the response of synoviocytes to apoptotic stimulation. Also, mitochondrial abnormalities in synoviocytes promote the synoviocytes invasion and proliferation.
33632596 TGF-β1 +869T/C (rs1982073) gene polymorphism and susceptibility to rheumatoid arthritis: 2021 May Rheumatoid arthritis (RA) is a complex autoimmune disease that affects about 1% of the world's population. The conclusions about the relationship between TGF gene polymorphism and the risk of RA are still inconsistent. Therefore, we performed a meta-analysis to re-evaluate the relationship between TGF-β1 T869C gene polymorphism and the risk of rheumatoid arthritis. METHOD: We performed a systematic electronic search in PubMed, Embase, Elsevier, Web of Science, Cochrane Library, Medline and China National Knowledge Infrastructure database (up to August 2020). In the subgroup analysis, we divide the research into three groups: Asian, European and Mediterranean, The combined OR and 95%CI of the five models (allele model, homozygous model, heterozygous model, dominant model, recessive model) were calculated, respectively. RESULTS: 15 case-control studies (14 articles) were involved in this meta-analysis, including 2103 cases and 2143 healthy controls. In the overall analysis, it showed that there may be an significant association between TGF-β1+869T/C polymorphism and RA sensitivity (allele model, T vs. C: OR=1.444, 95% CI=1.171-1.782, P=0.001; homozygous model, TT vs. CC: OR=1.910, 95% CI=1.322-2.761, P=0.001; heterozygous model, CT vs. CC: OR=1.558, 95% CI=1.179-2.059,P=0.002; dominant model, TT+CT vs. CC: OR= 1.742, 95% CI=1.303-2.329, P=0.001; recessive model, TT vs. CT+CC: OR=1.400, 95% CI= 1.058-1.852, P=0.018).However, the results of ethnic subgroup analysis indicated that rs1982073 was not associated with RA risk in Europeans(allele model, T vs. C: OR=0.993, 95% CI=0.849-1.162, P=0.931, I(2) <0.1%, P>0.1). CONCLUSION: In summary, our meta-analysis showed that the rs1982073 T allele does not increase RA susceptibility in Europeans.
34175381 Hepatotoxic potentials of methotrexate: Understanding the possible toxicological molecular 2021 Jun 30 Methotrexate (MTX) is one of the most effective and widely used drugs in the management of autoimmune and dermatological diseases. Rheumatoid arthritis and psoriasis patients who are under long term MTX-therapy are at high risk of developing a liver injury. Accumulation of intracellular MTX-polyglutamate (MTX-PG), a metabolite of MTX triggers oxidative stress, inflammation, steatosis, fibrosis, and apoptosis in hepatocytes. MTX-PG causes oxidative stress in the liver by inducing lipid peroxidation thereby releasing reactive oxygen species and suppressing antioxidant response elements. MTX-PG induces several pro-inflammatory signaling pathways and cytokines such as tumor necrosis factor-α, nuclear factor kappa B and interleukin 6 (IL-6), IL- β1, IL-12. MTX-PG depletes hepatic folate level and decreases RNA and DNA synthesis leading to hepatocyte death. MTX-PG inhibits 5-aminoimidazole-4-carboxamide ribonucleotide transformylase enzyme and thereby causes accumulation of intracellular adenosine, which causes activation of hepatic stellate cells, extracellular matrix accumulation and hepatic fibrosis. MTX-PG induces hepatocytes apoptosis by activation of caspase 3 via the intrinsic pathway. Clinically, aggravation of underlying fatty liver to non-alcoholic steatohepatitis with fibrosis seems to be an important mechanism of liver injury in MTX-treated RA patients. Therefore, there is a need for monitoring liver injury in RA, psoriatic and cancer patients with NAFLD and fibrosis risk factors during MTX treatment. This review summarizes the possible molecular mechanism of MTX-induced hepatotoxicity. It may pave the way for early detection of liver injury and develop novel strategies for treating MTX mediated hepatotoxicity.
32342712 Tocilizumab, an anti-interleukin-6 receptor antibody, efficiently ameliorates persistent j 2021 Jan OBJECTIVES: To assess the efficacy of tocilizumab (TCZ) in the treatment of persistent arthritis in patients with rheumatoid arthritis (RA). METHODS: The response to TCZ was evaluated in 304 patients with RA. TCZ treatment was completed after no fewer than 168 consecutive days between 28 May 2008 and 31 July 2019. Efficacy was evaluated using the DAS28-ESR and EULAR response criteria. RESULTS: The mean DAS28-ESR decreased from 4.5 at baseline to 2.0 and 1.5, at 2 months and 1 year after treatment initiation, respectively, and was below 1.5 at 10 years. The retention rate within 1 year was 92.3%. TCZ re-administration to 74 patients with relapsed RA after TCZ withdrawal was also effective. The mean DAS28-ESR decreased from 4.4 at baseline to 1.8 and 1.6 at 2 months and 1 year after retreatment initiation, respectively. The mean swollen joint count decreased from 4.1 in initial TCZ administration and 2.8 in re-administration at baseline to 0.8 and 0.4 at 2 months, respectively. In all patients, good or moderate responses were achieved at least once within 12 months in both initial TCZ administration and re-administration. CONCLUSION: TCZ efficiently ameliorated persistent arthritis in RA, regardless of initial administration and re-administration.
34966821 Bibliometric Analysis of the Scientific Literature on Rheumatoid Arthritis-Associated Inte 2021 BACKGROUND: In recent years, the number of studies on rheumatoid arthritis-related interstitial lung disease (RA-ILD) has been increasing, which has led to many publications on this topic. Our purpose is to identify research trends in RA-ILD and analyze the most-cited RA-ILD-related high-quality scientific publications. METHODS: All publications on RA-ILD in the Core Collection database of Web of Science were searched. The publication year, country, institution, total citations, and journal were extracted and analyzed. We used VOSviewer software or an online bibliometric analysis platform for cooccurrence analysis of the keywords, institutions, and countries involved. The 100 most frequently cited RA-ILD publications were analyzed. RESULTS: In total, 596 publications related to RA-ILD were obtained. Over time, the frequency of RA-ILD publications has increased. Globally, the United States provides the most publications on RA-ILD (n = 195). The institution with the highest publication output was the Mayo Clinic (n = 43). The journal "Annals of the Rheumatic Diseases" published most with 93 articles and received 338 citations. A clinical description was the most common research topic in RA-ILD-related publications. CONCLUSIONS: In recent years, there has been an increasing number of studies on RA-ILD, and related publications have increased rapidly. This study is the first bibliometric study of RA-ILD-related publications. It can be used as a guide for clinicians and can help researchers choose research directions of interest in this field.
34854396 MiR-125a-3p inhibits cell proliferation and inflammation responses in fibroblast-like syno 2021 Dec 1 OBJECTIVES: To explore the role and mechanism of miR-125a-3p in rheumatoid arthritis (RA) progression. METHODS: The RA-tissues and fibroblast-like synovial cells in rheumatoid arthritis (RA-FLS) were used in this study. qRT-PCR, western blot and ELISA assay were performed to detect the expression levels of IL-6, IL-β and ΤΝF-α. Dual-luciferase reporter gene assay was used to observe the binding effect of miR-125a-3p and MAST3, and CCK-8 was used to observe the effect of miR-125a-3p on the proliferation of RA-FLS. RESULTS: miR-125a-3p was significantly downregulated in the RA-tissues and RA-FLS, and miR-125a-3p could inhibit the proliferation and reduce the inflammation response of RA-FLS. Besides, MAST3 was found as a target of miR-125a-3p, and increased MAST3 could reverse the effects of miR-125a-3p on RA-FLS including decreased proliferation, reduced inflammation level and the inactivation of Wnt/β-catenin and NF-κB pathways. CONCLUSIONS: This study suggests that miR-125a-3p could inactivate the Wnt/β-catenin and NF-κB pathways to reduce the proliferation and inflammation response of RA-FLS via targeting MAST3.
33458774 Influence of inflammatory and non-inflammatory rheumatic disorders on the clinical and bio 2021 Aug 2 OBJECTIVE: To study the profile of type-2 diabetes (T2D) in patients with RA or OA. METHODS: This observational, multicentre, cross-sectional study included, over a 24-month period, consecutive patients with adult-onset diabetes and RA or OA. We collected demographics, disease activity and severity indices, current treatments for RA and diabetes, history and complications of diabetes. A systematic blood test was performed, assessing inflammatory, immunological and metabolic parameters. The homoeostasis model assessment (HOMA)2-S was used to assess insulin resistance. RESULTS: We included 167 patients with T2D, 118 with RA and 49 with OA. RA and OA patients had severe T2D with suboptimal metabolic control and a biological profile of insulin resistance. Insulin resistance was significantly higher in RA than in OA patients after stratification on age, BMI and CS use [HOMA2-S: 63.5 (35.6) vs 98.4 (69.2), P < 0.001]. HOMA2-S was independently associated with DAS28 [odds ratio (OR): 4.46, 95% CI: 1.17, 17.08]. T2D metabolic control was not related to disease activity and functional impairment, but HbA1c levels were independently associated with bone erosions (OR: 4.43, 95% CI: 1.18, 16.61). Treatment with low-dose CSs was not associated with decreased insulin sensitivity or increased HbA1c levels. Treatment with TNF-α inhibitors was associated with increased insulin sensitivity compared with patients not receiving biologics [101.3 (58.71) vs 60.0 (32.5), P = 0.001]. CONCLUSION: RA patients display severe T2D with inflammation-associated insulin resistance. These findings may have therapeutic implications, with the potential targeting of insulin resistance through the treatment of joint and systemic inflammation.