Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
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30109509 | Inflammatory dietary pattern and risk of developing rheumatoid arthritis in women. | 2019 Jan | Our objective was to investigate whether a dietary pattern derived using inflammatory biomarkers is associated with rheumatoid arthritis (RA) risk. We prospectively followed 79,988 women in the Nurses' Health Study (NHS, 1984-2014) and 93,572 women in the NHSII (1991-2013); incident RA was confirmed by medical records. Food frequency questionnaires (FFQ) were completed at baseline and approximately every 4 years. Inflammatory dietary pattern was assessed from FFQ data using the Empirical Dietary Inflammatory Pattern (EDIP), including 18 anti-/pro-inflammatory food/beverage groups weighted by correlations with plasma inflammatory biomarkers (interleukin-6, C-reactive protein, and tumor necrosis factor-α receptor 2). We investigated associations between EDIP and RA using Cox regression. We identified 1185 incident RA cases over 4,425,434 person-years. EDIP was not associated with overall RA risk (p trend = 0.21 across EDIP quartiles). Among women ≤ 55 years, increasing EDIP was associated with increased overall RA risk; HRs (95% CIs) across EDIP quartiles were 1.00 (reference), 1.14 (0.86-1.51), 1.35 (1.03-1.77), and 1.38 (1.05-1.83; p for trend = 0.01). Adjusting for BMI attenuated this association. Increasing EDIP was associated with increased seropositive RA risk among women ≤ 55 years (p for trend = 0.04). There was no association between EDIP and RA among women > 55 years (EDIP-age interaction, p = 0.03). An inflammatory dietary pattern was associated with increased seropositive RA risk with onset ≤ 55 years old, and this association may be partially mediated through BMI. | |
30205984 | Osteoporosis Self-Assessment Tool As a Screening Tool for Predicting Osteoporosis in Elder | 2019 Jul | Osteoporosis Self-Assessment Tool for Asians (OSTA) is an indicator for assessing osteoporosis in postmenopausal women. The aim of this study was to investigate the value of OSTA index on predicting osteoporosis in elderly Chinese patients with established rheumatoid arthritis (RA). A total of 320 patients with RA and 158 normal individuals were recruited from January 2015 to October 2017. Bone mineral density (BMD) at the femur and lumbar spine was measured by dual-energy X-ray absorptiometry. RA group and control group were divided into low risk (values≥-1), medium risk (values between -4 and -1), and high risk (values ≤-4) group according to the value of OSTA index. One-way analysis of variance showed that BMD at all detected regions among the 3 groups were obviously different (p < 0.0001). Incidences of osteoporosis among different OSTA groups were 21.76% (47/216), 56.41% (44/78), and 80.77% (21/26), separately (x(2) = 67.389, p < 0.0001). In RA group including premenspausal or postmenspausal female subgroup, prevalences of osteoporosis among different OSTA groups were different (p < 0.05-0.0001). We also found a positive linear correlation between OSTA index and BMD (p < 0.0001) both in RA and in control groups. Logistic regression revealed OSTA index (odds ratio = 0.734, p < 0.0001, 95% confidence interval: 0.657-0.819) was a protective factor for occurrence of RA-induced osteoporosis. OSTA had the highest discriminatory power, with an estimated Area Under Curve (AUC) of 0.750 (95% confidence interval 0.694-0.807, p < 0.0001), sensitivity of 76.9% and specificity of 66.5%. Our findings indicated that OSTA index was closely associated with BMD in RA patients, the degree of correlation was much stronger than age or BMI. OSTA index was a predictor for osteoporosis in RA, but it might have little relationship with disease status in RA. | |
29361739 | Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Lig | 2018 Jan 21 | Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50-60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles encode a conserved sequence of amino acids, referred to as the shared epitope (SE) structure. By analyzing the structure of a HLA-DR molecule in complex with Epstein-Barr virus (EBV), the SE motif is suggested to play a vital role in the interaction of MHC II with the viral glycoprotein (gp) 42, an essential entry factor for EBV. EBV has been repeatedly linked to RA by several lines of evidence and, based on several findings, we suggest that EBV is able to induce the onset of RA in predisposed SE-positive individuals, by promoting entry of B-cells through direct contact between SE and gp42 in the entry complex. | |
30418124 | Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin se | 2019 May | OBJECTIVES: In patients with rheumatoid arthritis (RA), insulin resistance (IR), a component of the metabolic syndrome, is closely linked to the systemic inflammation induced by proinflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-6. In the present study, we aimed to assess if an intravenous administration of the anti-IL-6 receptor tocilizumab may yield a rapid improvement of IR in RA. METHODS: 50 consecutive non-diabetic patients with RA refractory to methotrexate, undergoing periodic treatment with tocilizumab, were studied. Besides disease activity, serum insulin, insulin/glucose ratio, insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) indexes were assessed immediately before and 1 hour after the end of an intravenous administration of tocilizumab (given in saline solution over 60 minutes). RESULTS: When comparing baseline data (immediately before) and 1 hour after finishing tocilizumab administration, we observed a dramatic decrease of the serum insulin levels and insulin/glucose ratio. Also, a statistically significant reduction of IR (HOMA-IR: mean± standard deviation immediately before: 2.62±2.03 vs. 1.65±1.15 1 hour after the end of the infusion (p<0.01) and a statistically significant increase of insulin sensitivity (QUICKI immediately before 0.34±0.03 vs. 0.37±0.04 1 hour after the end of tocilizumab infusion (p<0.01) was observed. CONCLUSIONS: The intravenous administration of tocilizumab yields a rapid beneficial effect on IR and insulin sensitivity in non-diabetic RA patients. These findings support the potential beneficial effect of the IL-6 blockade on the mechanisms associated with the development of metabolic syndrome and cardiovascular disease in patients with RA. | |
30338649 | Incidence and risk factors for reactivation from resolved hepatitis B virus in rheumatoid | 2019 Apr | AIM: To identify the incidence and risk factors for hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients with resolved HBV receiving biological disease-modifying antirheumatic drugs (bDMARDs). METHOD: Rheumatoid arthritis patients in whom bDMARD therapy was initiated in our departments from April 2009 to July 2016 were reviewed. The patients diagnosed with resolved HBV and whose HBV-DNA levels had been repeatedly measured were enrolled. The endpoint was HBV reactivation (a positive conversion of HBV-DNA or unquantifiable cases with positivity <20 IU/mL). Nucleic acid analogues (NAAs) were administered when the HBV-DNA levels increased beyond 20 IU/mL. The associations between HBV reactivation and the clinical findings were retrospectively analyzed. RESULTS: One hundred and fifty-two RA patients with resolved HBV were enrolled; 133 (88%) patients had antibodies against HBV surface antigen (anti-HBs). The medicines that were administered included: abatacept (n = 29), golimumab (n = 26), etanercept (n = 25), tocilizumab (n = 25), adalimumab (n = 19), infliximab (n = 17) and certolizumab pegol (n = 11). During the observation period (15 [interquartile range 4.0-34] months), 7 (4.6%) patients developed HBV reactivation. In 5 of these patients, the HBV-DNA levels became negative or remained at <20 IU/mL (+) without NAA therapy. HBV-DNA levels of >20 IU/mL were observed in 2 patients but the HBV-DNA levels became negative after NAA treatment. Patients who were negative for anti-HBs showed a significantly higher incidence of HBV reactivation (P = 0.013). CONCLUSION: HBV reactivation occurred in 4.6% of RA patients with resolved HBV during the treatment with bDMARDs and the absence of anti-HBs may be a risk factor for the reactivation of resolved HBV. | |
29121263 | High prevalence of diabetes in patients with rheumatoid arthritis: results from a question | 2018 Feb 1 | OBJECTIVES: To investigate the prevalence of diabetes in patients with RA and the impact of diabetes on self-reported outcomes and health care. METHODS: RA patients between the ages of 18 and 79 years were randomly selected from a nationwide statutory health insurance fund and were surveyed about rheumatological care and disease burden. Comorbid diabetes (E10-14) was analysed regarding age, sex, BMI and socioeconomic status. Disease burden, comorbidity and prescriptions were compared in RA patients with and without diabetes. Predictors of rheumatological care were identified by multivariate regression. RESULTS: Of the 2535 RA patients, 498 (20%) had diabetes. Diabetes was more frequent in males, in older patients, in patients with a higher BMI and in those with a lower socioeconomic status. All disease outcomes were poorer in RA-diabetes patients and were mainly attributable to a higher BMI. RA-diabetes patients received less DMARDs (40% vs 48%) and had more hospital stays (41% vs 30%) than patients without diabetes (all P < 0.05). Rates of cardiovascular disease (35% vs 15%), depression (39% vs 26%) and renal failure (23% vs 8%) were higher in RA-diabetes patients (all P < 0.0001). They were less frequently treated by rheumatology specialists: 57% vs 67%; odds ratio = 0.64 (95% CI: 0.45, 0.92), after controlling for confounders. CONCLUSION: The prevalence of diabetes in patients with RA is high and is associated with known sociodemographic factors. More than 40% of patients with RA and diabetes were not under rheumatological care even though they reported a high disease burden, were frequently hospitalized and often presented with further comorbidities. | |
30504676 | Minimum Infliximab Dosage for Keeping Serum Infliximab Levels Greater than 1 µg/mL amon | 2018 | Infliximab shows drastic efficacy for controlling inflammation in rheumatoid arthritis (RA), though the ideal dose of infliximab to keep suppressing inflammation has not yet been identified. Recently, it has been evidenced that the minimum trough serum infliximab levels required for suppressing inflammation are greater than 1 µg/mL. This cross-sectional study was designed to identify the minimum dosage of infliximab for maintaining serum infliximab levels greater than 1 µg/mL. Thirty seven RA patients were enrolled in this study and they were divided into two groups (high-infliximab vs. low-infliximab) in reference to Remi-check Q(®), a kit for examining serum infliximab levels above/below 1 µg/mL by LC. Infliximab dosage (p=0.06) and dosage interval (p=0.05) had trends to have differences between groups. A formula calculated by infliximab dosage divided by dosage interval and body weight (mg/weeks/kg) was shown to have significantly higher levels among high-infliximab group (p=0.04). Based on whether serum infliximab levels above/below 1 µg/mL and values led by the equation, infliximab dosage/infliximab interval/body weight (mg/weeks/kg), a receiver operating characteristic curve (ROC) was depicted with area under the ROC curve 0.750 and the cut-off point for the serum infliximab levels greater than 1 µg/mL was identified as infliximab dosage/infliximab interval/body weight ≧0.750 with the sensitivity 0.393 and the specificity 1.000. In conclusion, we identified that the minimum infliximab dosage to maintain serum infliximab levels greater than 1 µg/mL was infliximab dose/dosage interval/body weight (mg/weeks/kg)≥0.750. | |
28967235 | Addressing rural and remote access disparities for patients with inflammatory arthritis th | 2018 Mar | OBJECTIVE: The aim of the present study was to evaluate whether rheumatoid arthritis (RA) patients followed longitudinally using video-conferencing and inter-professional care support have comparable disease control to those followed in traditional in-person rheumatology clinics. METHODS: This was a randomized controlled trial for 85 RA patients allocated to either traditional in-person rheumatology follow-up or video-conferenced follow-up with urban-based rheumatologists and rural in-person physical therapist examiners. Follow-up was every 3Â months for 9Â months. Outcome measures included disease activity metrics (disease activity in 28 joints with CRP measure score [DAS28-CRP], and RA disease activity index [RADAI]), modified health assessment questionnaire (mHAQ), quality of life (EuroQOL five dimensions questionnaire [EQ5D]) and patient satisfaction (nine-item visit-specific satisfaction questionnaire [VSQ9]). RESULTS: Of 85 participants, 54 were randomized to the video-conferencing team model and 31 to the traditional clinic (control group). Dropout rates were high, with only 31 (57%) from the video-conferencing and 23 (74%) from the control group completing the study. The mean age for study participants was 56Â years; 20% were male. Mean RA disease duration was 13.9Â years. There were no significant between-group differences in DAS28-CRP, RADAI, mHAQ or EQ5D scores at baseline or over the study period. Satisfaction rates were high in both groups. CONCLUSIONS: We found no evidence of a difference in effectiveness between inter-professional video-conferencing and traditional rheumatology clinic for both the provision of effective follow-up care and patient satisfaction for established RA patients. High dropout rates reinforce the need for consultation with patients' needs and preferences in developing models of care. While use of video-conferencing/telehealth technologies may be a distinct advantage for some patients, there may be loss of travel-related auxiliary benefits for others. | |
29696436 | Prevalence of cardiovascular disease and major risk factors in patients with rheumatoid ar | 2018 Sep | To compare the prevalence of cardiovascular disease (CVD) and major CVD risk factors among rheumatoid arthritis (RA) patients enrolled in a large US and multinational registry. We compared CVD and CVD risk factor prevalence from 11 countries enrolled in the CORRONA US and CORRONA International registries; patients from the 10 ex-US participating countries were grouped by region (Eastern Europe, Latin America, and India). Unadjusted summary data were presented for demographics and disease characteristics; comparisons for prevalence of CVD risk factors and CVD were age/gender standardized to the age/gender distribution of the US enrolled patients. Overall, 25,987 patients were included in this analysis. Compared to patients from the ex-US regions, US participants had longer disease duration and lower disease activity, yet were more likely to receive a biologic agent. Additionally, CORRONA US participants had the highest body mass index (BMI). Enrolled patients in India had the lowest BMI, were more rarely smokers, and had a low prevalence of hyperlipidemia, hypertension, and prior CVD compared to the US and other ex-US regions. Participants from Eastern Europe had a higher prevalence of hypertension and hyperlipidemia and highest prevalence of all manifestations of CVD. Differences in the prevalence of both CVD and major CVD risk factors were observed across the four regions investigated. Observed differences may be influenced by variations in both non-modifiable/modifiable characteristics of patient populations, and may contribute to heterogeneity on the observed safety of investigational and approved therapies in studies involving RA patients from different origins. | |
28485187 | Tumour necrosis factor-α/etanercept complexes in serum predict long-term efficacy of etan | 2018 Jan | OBJECTIVE: To study whether serum levels of tumour necrosis factor-α (TNF-α), free or bound to etanercept, in biological-naïve adults with rheumatoid arthritis (RA) could predict the long-term efficacy of etanercept, measured as drug survival. METHOD: We identified 145 biological-naïve patients with RA starting treatment with etanercept at the Department of Rheumatology, Skåne University Hospital (1999-2008), of whom 16 had seronegative and 129 seropositive RA. TNF-α in serum was quantified using enzyme-linked immunosorbent assay in samples from the onset of treatment and at 6 week follow-up. Drug survival time was used to evaluate the long-term efficacy of etanercept. RESULTS: Levels of TNF-α were significantly increased at follow-up compared to at the start. At the 6 week follow-up, circulating TNF-α mainly comprised TNF-α in complex with etanercept. Longer drug survival time correlated with increased TNF-α at 6 week follow-up in the patients with seronegative RA, but not in the seropositive patients. CONCLUSION: We demonstrated that levels of circulating TNF-α increased in almost all individuals after initiation of treatment with etanercept and that this increase mainly comprised TNF-α in complex with etanercept. More importantly, this increase may predict drug survival in adults with seronegative, but not seropositive, RA and suggests that measuring TNF-α/etanercept complexes in serum may be relevant in patients with seronegative RA. | |
29751535 | Therapeutic Potential of Sclareol in Experimental Models of Rheumatoid Arthritis. | 2018 May 3 | Previous studies have shown that the natural diterpene compound, sclareol, potentially inhibits inflammation, but it has not yet been determined whether sclareol can alleviate inflammation associated with rheumatoid arthritis (RA). Here, we utilized human synovial cell line, SW982, and an experimental murine model of rheumatoid arthritis, collagen-induced arthritis (CIA), to evaluate the therapeutic effects of sclareol in RA. Arthritic DBA/1J mice were dosed with 5 and 10 mg/kg sclareol intraperitoneally every other day over 21 days. Arthritic severity was evaluated by levels of anti-collagen II (anti-CII) antibody, inflammatory cytokines, and histopathologic examination of knee joint tissues. Our results reveal that the serum anti-CII antibody, cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-17, as well as Th17 and Th1 cell population in inguinal lymph nodes, were significantly lower in sclareol-treated mice compared to the control group. Also, the sclareol treatment groups showed reduced swelling in the paws and lower histological arthritic scores, indicating that sclareol potentially mitigates collagen-induced arthritis. Furthermore, IL-1β-stimulated SW982 cells secreted less inflammatory cytokines (TNF-α and IL-6), which is associated with the downregulation of p38-mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and NF-κB pathways. Overall, we demonstrate that sclareol could relieve arthritic severities by modulating excessive inflammation and our study merits the pharmaceutical development of sclareol as a therapeutic treatment for inflammation associated with RA. | |
29616452 | Flavonoid quercetin-methotrexate combination inhibits inflammatory mediators and matrix me | 2018 Oct | Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovial tissues in joints, leading to progressive destruction of cartilage and joints. The disease-modifying anti-rheumatic drugs currently in use have side-effects. Thus, there is an urgent need for safe anti-inflammatory therapies for RA. This study aimed to evaluate the therapeutic effect of the flavonoid quercetin on arthritis in mice immunized with type II collagen (CII). An arthritis model was established in C57/BL6 mice by intradermal administration of chicken CII mixed with Freund's complete adjuvant. Quercetin (30 mg/kg orally) and methotrexate (0.75 mg intraperitoneally twice a week) were administered to investigate their protective effects against collagen-induced arthritis (CIA). Levels of tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and the matrix metalloproteinases (MMP), 3, and 9 were detected to assess the anti-inflammatory effect of quercetin. The mRNA expression of MMP3, MMP9, CCL2, and TNF-α was also measured by quantitative real-time PCR. Quercetin significantly alleviated joint inflammation by reducing the levels of circulating cytokines and MMPs. There was a significant decrease in the expression of TNFα and MMP genes in the ankle joints of arthritic mice. A significant reduction in the levels of knee-joint inflammatory mediators were observed with combined quercetin and methotrexate treatment. Thus, quercetin has the potential to prevent joint inflammation and could be used as an adjunct therapy for RA patients who have an inadequate response to anti-rheumatic monotherapy. | |
29463520 | Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib | 2018 Jul | OBJECTIVES: Lipid profiles are altered by active disease in patients with rheumatoid arthritis (RA) and may be further modified by treatment with Janus kinase inhibitors and other disease-modifying antirheumatic drugs. METHODS: Lipid data were analysed from phase II and III studies of 4 mg (n=997) and 2 mg (n=479) oral baricitinib administered once daily in patients with moderate-to-severe active RA. Lipoprotein particle size and number and GlycA were evaluated with nuclear magnetic resonance in one phase III study. The effect of statin therapy on lipid levels was evaluated in patients on statins at baseline and in patients who initiated statins during the study. RESULTS: Treatment with baricitinib was associated with increased levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides, but no significant change in LDL-C:HDL-C ratio. Lipid levels plateaued after 12 weeks of treatment. Baricitinib treatment increased large LDL and decreased small, dense LDL particle numbers and GlycA. Lipid changes from baseline were not significantly different between baseline statin users and non-users. In patients who initiated statin therapy during the study, LDL-C, triglycerides (baricitinib 4 mg only) and apolipoprotein B decreased to pre-baricitinib levels; HDL-C and apolipoprotein A-I levels remained elevated. CONCLUSIONS: Baricitinib was associated with increased LDL-C, HDL-C and triglyceride levels, but did not alter the LDL-C:HDL-C ratio. Evaluation of cardiovascular event rates during long-term treatment is warranted to further characterise these findings and their possible clinical implications. TRIAL REGISTRATION NUMBER: NCT00902486, NCT01469013, NCT01185353, NCT01721044, NCT01721057, NCT01711359, NCT01710358, NCT01885078. | |
30581068 | Interleukin-13: A promising therapeutic target for autoimmune disease. | 2019 Feb | Interleukin-13 (IL-13) was previously thought to be a redundant presence of IL-4, but in recent years its role in immunity, inflammation, fibrosis, and allergic diseases has become increasingly prominent. IL-13 can regulate several subtypes of T helper (Th) cells and affect their transformation, including Th1, Th2, T17, etc., thus it may play an important role in immune system. Previous studies have revealed that IL-13 is implicated in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), ulcerative colitis (UC), type 1 diabetes (T1D), sjogren's syndrome (SS), etc. In this review, we will briefly discuss the biological features of IL-13 and summarize recent advances in the role of IL-13 in the development and pathogenesis of autoimmune diseases. This information may provide new perspectives and suggestions for the selection of therapeutic targets for autoimmune diseases. | |
30562687 | Preparation, characterization and application of anti-human OX40 ligand (OX40L) monoclonal | 2019 Feb | OX40L (CD252, TNFSF4), a type II transmembrane protein which like other tumor necrosis factor ligands, involved in the costimulation and differentiation of T cells, functions as a positive signal in immune response. To investigate the biological function of soluble OX40L (sOX40L), three functional anti-OX40L monoclonal antibodies (mAbs) 3D2, 3F7 and 2H3 were obtained by hybridoma technology. Besides, specificity of the mAbs was further demonstrated by ELISA, Western blot and Immunofluorescence experiments. We also developed a novel enzyme-linked immunosorbent assay (ELISA) based on two anti-human OX40L antibodies 3D2 and 3F7 with different epitopes. Using the ELISA system, we found that sOX40L in the sera of healthy donors increases in an age-dependent manner and that enhanced sOX40L expression in some autoimmune diseases especially in rheumatoid arthritis (RA) patients, suggesting the potential diagnostic significance of sOX40L in the autoimmune diseases. Together, these data demonstrate that the existence of circulating sOX40L in human sera might play an important role in immunoregulation. | |
29997111 | Glucocorticoid receptor in stromal cells is essential for glucocorticoid-mediated suppress | 2018 Nov | BACKGROUND: Glucocorticoid (GC) therapy is frequently used to treat rheumatoid arthritis due to potent anti-inflammatory actions of GCs. Direct actions of GCs on immune cells were suggested to suppress inflammation. OBJECTIVES: Define the role of the glucocorticoid receptor (GR) in stromal cells for suppression of inflammatory arthritis. METHODS: Bone marrow chimeric mice lacking the GR in the hematopoietic or stromal compartment, respectively, and mice with impaired GR dimerisation (GR(dim)) were analysed for their response to dexamethasone (DEX, 1 mg/kg) treatment in serum transfer-induced arthritis (STIA). Joint swelling, cell infiltration (histology), cytokines, cell composition (flow cytometry) and gene expression were analysed and RNASeq of wild type and GR(dim) primary murine fibroblast-like synoviocytes (FLS) was performed. RESULTS: GR deficiency in immune cells did not impair GC-mediated suppression of STIA. In contrast, mice with GR-deficient or GR dimerisation-impaired stromal cells were resistant to GC treatment, despite efficient suppression of cytokines. Intriguingly, in mice with impaired GR function in the stromal compartment, GCs failed to stimulate non-classical, non-activated macrophages (Ly6C(neg), MHCII(neg)) and associated anti-inflammatory markers CD163, CD36, AnxA1, MerTK and Axl. Mice with GR deficiency in FLS were partially resistant to GC-induced suppression of STIA. Accordingly, RNASeq analysis of DEX-treated GR(dim) FLS revealed a distinct gene signature indicating enhanced activity and a failure to reduce macrophage inflammatory protein (Mip)-1α and Mip-1β. CONCLUSION: We report a novel anti-inflammatory mechanism of GC action that involves GR dimerisation-dependent gene regulation in non-immune stromal cells, presumably FLS. FLS control non-classical, anti-inflammatory polarisation of macrophages that contributes to suppression of inflammation in arthritis. | |
30285829 | CYLD suppression enhances the pro-inflammatory effects and hyperproliferation of rheumatoi | 2018 Oct 3 | BACKGROUND: Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) actively drive joint inflammation and degradation by producing inflammatory cytokines and matrix-degrading molecules, making them key factors in the pathogenesis of RA. Cylindromatosis (CYLD) is a tumor suppressor that downregulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation by deubiquitinating NF-κB essential modulator and tumor necrosis factor receptor-associated factors 2 and 6. In this study, we aimed to determine CYLD expression in the synovium of patients with RA, analyze its correlation with NF-κB activation and clinical disease activity, further investigate CYLD expression in RA-FLSs, and explore CYLD's roles and mechanisms in the pro-inflammatory effects, proliferation, apoptosis, and cell cycles of RA-FLSs. METHODS: We obtained synovia from 50 patients with active RA and 20 with osteoarthritis (OA) and then cultured FLSs from the samples. We determined CYLD expression in the synovia of RA patients and in FLSs via reverse transcription polymerase chain reaction (RT-PCR). CYLD was depleted by lentiviral CYLD short hairpin ribonucleic acid. We used RT-PCR and enzyme-linked immunosorbent assay to analyze the expression of pro-inflammatory cytokines, matrix metalloproteinases (MMPs), and receptor activator of nuclear factor kappa-B ligand (RANKL). We detected cell proliferation using Cell Counting Kit-8 and examined cell apoptosis and cell cycle using flow cytometry. RESULTS: We obtained the following results: 1. In synovia from patients with RA, CYLD expression was significantly downregulated while NF-κB expression was distinctly upregulated, compared with synovia from patients with OA. Thus, there is a significant inverse correlation between CYLD and NF-κB in synovia affected by RA. 2. CYLD expression significantly decreased in RA-FLSs compared with OA-FLSs. 3. CYLD suppression enhanced the production of pro-inflammatory cytokines, MMPs, and RANKL by activating NF-κB in RA-FLSs. 4. CYLD suppression enhanced proliferation, reduced apoptosis, and increased cell division of RA-FLSs and aggravated the activity of NF-κB in RA-FLSs. CONCLUSIONS: Via its regulation of NF-κB activation, CYLD may be involved in the pathogenesis of synovial inflammation in RA as well as in the pro-inflammatory effects and hyperproliferation of RA-FLSs. CYLD may therefore provide a potential target for the treatment of RA. | |
30657075 | Staying in the labor force among patients with rheumatoid arthritis and associated factors | 2018 Jul 11 | BACKGROUND: Rheumatoid arthritis primarily affects the working-age population and may cause key functional and work limitations. As the disease progresses, individuals become increasingly unable to conduct daily activities, which has a substantial personal and socioeconomic impact. Fairly recent prior studies showed that patients with RA stop working 20 years earlier than age-matched controls. Factors related to sociodemographic, clinical, care and disease profiles might affect the loss of work capacity. The purpose of this study was to assess the factors associated with the prevalence of working patients with rheumatoid arthritis in the municipality of Blumenau. METHODS: A cross-sectional, population-based study was conducted between July 2014 and January 2015, with 296 individuals aged 20Â years or older, male and female, living in Blumenau, Santa Catarina state, Brazil, and diagnosed with rheumatoid arthritis according to the 1987 American College of Rheumatology criteria. The prevalence of working patients with RA was assessed by employment status self-reporting during the interview. The chi-squared test, Wald test and Poisson regression analysis were used to test the possible associations between the independent variables and outcome. RESULTS: The prevalence of working patients with rheumatoid arthritis was 44.3%. Patients aged 20 to 59Â years had a 90% higher prevalence of outcome than subjects aged 60Â years or older. The prevalence of working patients was 132% and 73% higher among individuals with low income and high functional disability, measured using the Health Assessment Questionnaire (HAQ), respectively. CONCLUSION: The prevalence of working RA patients was highest among adult patients with low income and high functional disability. The first variable is directly related to the individual characteristic, the second reflects the socioeconomic context of the patient, and the third reflects the degree of disability caused by the disease, which may be modifiable by health professionals. | |
29761884 | Inhibitory effects of tubeimoside I on synoviocytes and collagen-induced arthritis in rats | 2018 Nov | Advancements in rheumatoid arthritis (RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential medicines with relative safety and efficacy continues and natural compounds have been considered as alternatives or complementary agents to gain immense attractions. Tubeimoside I (TBMS I), a main triterpenoid saponin isolated from Bolbostemma paniculatum, has been reported to possess antiviral and anticancer effects. However, its effect on RA remains unknown. Here, we investigated the therapeutic effect of TBMS I in collagen-induced arthritis (CIA) rats and explored its underlying mechanism. Our results showed that TBMS I treatment efficaciously ameliorated inflammation and joint destruction of rats with CIA. In vitro studies revealed that TBMS I suppressed the production of pro-inflammatory cytokines including IL-1β, IL-6, IL-8 and TNFα, and downregulated the expression of MMP-9. In addition, TBMS I attenuated the destructive phenotypes of FLS of CIA rats including inhibiting proliferation and reducing migration rate. Further mechanistic analysis demonstrated that TBMS I suppressed TNFα-induced activations of NF-κB and MAPKs (p38 and JNK) leading to the downregulation of pro-inflammatory cytokines, which was beneficial to the anti-proliferative and anti-migratory activities of FLS cells. Taken together, TBMS I has a great potential to be developed into a novel therapeutic agent for the treatment of RA. | |
30328025 | Contribution of the bone and cartilage/soft tissue components of the joint damage to the l | 2019 Mar | The study aims to analyze the association between the bone and cartilage/periarticular components of the radiographic joint damage and disability over the course of disease, in a cohort of rheumatoid arthritis (RA) patients from a day-to-day clinical practice. The secondary aim is to study the role of demographic and disease-related variables in this association. We performed a retrospective longitudinal study including 736 RA patients. Disability was assessed with the health assessment questionnaire (HAQ), and radiographic joint damage of hands and wrists with the Sharp van-der-Heijde score (total (SHS), erosion (ES), and narrowing/(sub)luxation (NSLS) components]. Generalized estimating equations models, adjusted by disease activity, demographic and disease-related variables, were used to test the relationship between SHS and medium-term (median value of the HAQs performed in the following year after each radiograph) and long-term (set of HAQ measures performed during follow-up, at least 1Â year apart from the first x-ray) disability. Interaction terms between the SHS and demographic and disease-related variables were introduced in the models. To account for multiple testing, Bonferroni correction was applied. NSLS was independently associated with medium-term disability, even after Bonferroni correction. We observed significant and positive interactions between NSLS and age at x-ray, and with the ES. SHS showed no association with long-term disability. The cartilage/soft tissue component of the radiographic joint damage seems to exert a much more important role in medium-term disability than the erosive component. This association could be modulated by the age at the x-ray and by the magnitude of the erosive damage. |