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ID PMID Title PublicationDate abstract
29992393 Adverse childhood experience and rheumatic diseases. 2018 Oct It has been suggested that the adaptive stress response may be disrupted by life adverse events such as childhood maltreatment. To investigate if the number of adverse childhood experiences (ACEs) increases susceptibility to systemic lupus erythematosus (SLE), spondyloarthritis (SpA), scleroderma (SSc), and rheumatoid arthritis (RA), we interviewed 315 patients with rheumatic disease (100 SLE; 40 SSc; 60 SpA; 115 RA) and 272 controls, using questions of the ACEs study questionnaire validated to ask about experiences of childhood abuse, negligence, domestic violence, and household dysfunctions. The questionnaire score ranges from zero (best result) to 8 (worst scenario). Patients and controls did not differ regarding the median number of ACEs (3 in both groups, patient IQR = 2.5-5 vs. control IQR = 2-5, p = 0.45). Among the patients, 63.8% (201/315) presented ACE score ≥ 3, compared with 59.9% (163/272) of the controls (p = 0.31). The proportion of patients with at least 3 ACEs did also not differ among those with different rheumatic diseases. Specifically, 64% (64/100) of those with SLE, 60% (24/40) of those with SSc, 60% (36/60) of those with SpA, and 66.9% (77/115) of those with RA reported at least 3 ACEs. There was also no difference between the distribution of ACE scores and number of individuals with ACEs ≥ 3 between patients with different rheumatic diseases and controls. Nevertheless, there was a trend for association between higher ACE score and susceptibility to RA (p = 0.06). In this setting, the occurrence of ACEs was not associated with susceptibility to rheumatic diseases in adulthood.
30054896 The Effectiveness of Intravenous Golimumab Administered Directly After Infliximab in Rheum 2018 Sep PURPOSE: For patients with rheumatoid arthritis (RA) who do not respond or lose response to anti-tumor necrosis factor (TNF) biologics, switching to a different anti-TNF can be an effective means to manage symptoms and disease progression. This study examined the utilization and effectiveness of intravenous golimumab within a real-world population of patients with RA switching directly from infliximab, a potent anti-TNF. METHODS: Patient charts (n = 113) were collected from five US-based rheumatology practices. Patient demographics, treatment characteristics, infliximab and intravenous golimumab utilization data, and Clinical Disease Activity Index (CDAI), Patient Global Assessment (PtGA), Physician Global Assessment (PhGA), and Routine Assessment of Patient Index Data (RAPID3) scores were extracted from charts. The effectiveness of intravenous golimumab was assessed by comparing disease activity status pre- and post-initiation of intravenous golimumab therapy. FINDINGS: Significant decreases in patient disease activity were observed following treatment with intravenous golimumab. Mean CDAI and PhGA scores significantly decreased, and a significantly increased proportion of the population exhibited low disease activity or remission in the post intravenous golimumab period (p < 0.05). Limited changes were observed through the RAPID3 and PtGA. CONCLUSIONS: Findings from this study indicate that intravenous golimumab is effective in managing RA in a population of patients switching directly from infliximab (mean last dose 7.4 mg/kg).
29997113 Apolipoprotein B binds to enolase-1 and aggravates inflammation in rheumatoid arthritis. 2018 Oct OBJECTIVE: Immune cells from patients with rheumatoid arthritis (RA) express more enolase-1 (ENO1) on their surface than those from healthy subjects, and they elicit an enhanced inflammatory response. This study is aimed to identify the ligands of ENO1 that could promote inflammatory loops in vitro and enhance the arthritis severity in vivo. METHODS: ENO1-binding proteins in RA synovial fluid were identified by mass spectromety, and affinity to ENO1 was evaluated by means of a ligand blotting and binding assay, surface plasmon resonance and confocal microscopy. Proinflammatory response by the interaction between ENO1 and apolipoprotein B (apoB) was tested in vitro and in vivo using peripheral blood mononuclear cells and a K/BxN serum transfer arthritis model and low-density lipoproteins receptor (LDLR) knockout mice. RESULTS: ApoB in the synovid fluid of patients with RA was identified as a specific ligand to ENO1 with a higher affinity than plasminogen, a known ENO1 ligand. ApoB binding to ENO1 on monocytes elicited the production of tumour necrosis factor-α, interleukins (IL)-1β and IL-6 through both p38 mitogen-activated protein kinase and NF-κB pathways. In the K/BxN serum transfer arthritis model, administration of apoB increased the production of proinflammatory cytokines and exaggerated arthritis severity. The severity of K/BxN serum transfer arthritis in LDLR knockout mice was comparable with wild-type mice. CONCLUSIONS: A key component of atherogenic lipids, apoB, aggravated arthritis by potentiating the inflammatory response via its interaction with ENO1 expressed on the surface of immune cells. This suggests a novel mechanism by which lipid metabolism regulates chronic inflammation in RA.
30209695 Risk of adverse outcomes in patients with rheumatoid arthritis hospitalized for stroke-a c 2018 Nov Specific data regarding the full range of stroke outcomes among patients with rheumatoid arthritis (RA) are lacking. This study aimed to investigate outcomes in RA patients hospitalized for a stroke. The study retrieved data from the Taiwan Longitudinal Health Insurance Database 2005. We identified 26,336 patients who were hospitalized for stroke treatment. Of these patients, 736 patients with a prior diagnosis of RA before the index hospitalization were selected as the study group. We selected 2208 age-sex-matched patients without RA as the comparison group. We performed conditional logistic regressions to calculate odds ratios (ORs) for in-hospital mortality and secondary diagnoses of pneumonia, urinary tract infections (UTIs), peptic ulcers, acute respiratory failure, and the use of mechanical ventilation to compare RA patients and comparison patients. We also compared the length of stay (LOS) and hospitalization costs between patients with RA and comparison patients. We found that RA patients had a significantly increased risk of peptic ulcer during the stroke hospitalization (OR = 1.52, 95% CI = 1.05-2.20). However, there were no significant differences between patients with RA and comparison patients in terms of in-hospital mortality, pneumonia, UTIs, acute respiratory failure, or the use of mechanical ventilation. Furthermore, the LOS of stroke hospitalization did not differ between the two groups. We concluded that RA patients hospitalized for a stroke do not have a significantly different risk of in-hospital mortality, pneumonia, UTIs, and mechanical ventilator use, but they have a higher risk of peptic ulcers. Additionally, among patients with a subarachnoid/intracerebral hemorrhagic stroke, RA patients were more likely to have received mechanical ventilation than comparison patients (adjusted OR = 1.89, 95% CI = 1.14-3.15).
30010481 Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthri 2018 Aug/Sep This multinational, randomized, double-blind trial, (ClinicalTrials.gov identifier NCT02149121) was designed to demonstrate equivalence in pharmacokinetics and efficacy between CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA). Adults with active RA were treated with CT-P10, United States-sourced RTX (US-RTX; Rituxan®), or European Union-sourced RTX (EU-RTX; MabThera®) at weeks 0 and 2. The co-primary pharmacokinetic endpoints were area under the serum concentration-time curve (AUC) from time zero to last measurable concentration (AUC(0-last)), AUC from time zero to infinity (AUC(0-∞)), and maximum concentration (C(max)) after two infusions. The primary efficacy endpoint was change from baseline to week 24 in Disease Activity Score using 28 joints-C-reactive protein (DAS28-CRP). Pharmacodynamics, immunogenicity, and safety were also assessed. 372 patients were randomly assigned to CT-P10 (n = 161) or RTX (n = 211 [US-RTX, n = 151; EU-RTX, n = 60]). For the co-primary pharmacokinetic endpoints, 90% confidence intervals (CI) for ratios of geometric means (CT-P10/US-RTX, CT-P10/EU-RTX or EU-RTX/US-RTX) all fell within the equivalence margin of 80-125%. Adjusted least squares (LS) mean (standard error) change from baseline in DAS28-CRP at week 24 was -2.13 (0.175) for CT-P10 and -2.09 (0.176) for RTX. The 95% CI (-0.29, 0.21) of the estimated treatment difference between CT-P10 and RTX (-0.04) was entirely within the efficacy equivalence margin of ±0.5. Pharmacodynamics, immunogenicity, and safety profiles were similar for CT-P10 and RTX. The pharmacokinetics of CT-P10, US-RTX, and EU-RTX were equivalent. CT-P10 and RTX were also equivalent in terms of efficacy and displayed similar pharmacodynamic, immunogenicity, and safety profiles up to week 24.
30504870 Identification of differentially methylated cell types in epigenome-wide association studi 2018 Dec An outstanding challenge of epigenome-wide association studies (EWASs) performed in complex tissues is the identification of the specific cell type(s) responsible for the observed differential DNA methylation. Here we present a statistical algorithm called CellDMC ( https://github.com/sjczheng/EpiDISH ), which can identify differentially methylated positions and the specific cell type(s) driving the differential methylation. We validated CellDMC on in silico mixtures of DNA methylation data generated with different technologies, as well as on real mixtures from epigenome-wide association and cancer epigenome studies. CellDMC achieved over 90% sensitivity and specificity in scenarios where current state-of-the-art methods did not identify differential methylation. By applying CellDMC to an EWAS performed in buccal swabs, we identified smoking-associated differentially methylated positions occurring in the epithelial compartment, which we validated in smoking-related lung cancer. CellDMC may be useful in the identification of causal DNA-methylation alterations in disease.
27920363 Detection of imprinting effects for qualitative traits on X chromosome based on nuclear fa 2018 Aug Methods for detecting imprinting effects have been developed primarily for autosomal markers. However, no method is available in the literature to test for imprinting effects on X chromosome. Therefore, it is necessary to suggest methods for detecting such imprinting effects. In this article, the parental-asymmetry test on X chromosome (XPAT) is first developed to test for imprinting for qualitative traits in the presence of association, based on family trios each with both parents and their affected daughter. Then, we propose 1-XPAT to deal with parent-daughter pairs, each with one parent and his/her affected daughter. By simultaneously considering family trios and parent-daughter pairs, C-XPAT (the combined test statistic of XPAT and 1-XPAT) is constructed to test for imprinting. Further, we extend the proposed methods to accommodate complete (with both parents) and incomplete (with one parent) nuclear families having multiple daughters of which at least one is affected. Simulation results demonstrate that the proposed methods control the size well, irrespective of the inbreeding coefficient in females being zero or non-zero. By incorporating incomplete nuclear families, C-XPAT is more powerful than XPAT using only complete nuclear families. For practical use, these proposed methods are applied to analyse the rheumatoid arthritis data and Turner's syndrome data.
29051108 A Bayesian model that jointly considers comparative effectiveness research and patients' p 2018 Jan OBJECTIVES: The objective of the study was to estimate the preferred treatment for early rheumatoid arthritis using a novel Bayesian approach that jointly considers patients' preferences and comparative effectiveness research. STUDY DESIGN AND SETTING: We estimated the preferred treatment using patients' preferences measured in a discrete-choice experiment to apply weights to benefit and harm outcomes from a network meta-analysis and other considerations (dosing, rare adverse events). Using Bayesian analyses, we considered the variability in patients' preferences and the imprecision in both patients' preferences and the treatment effects; all key considerations in the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: We estimated that most patients in our population would prefer triple therapy as initial treatment (78%) or after an inadequate response to methotrexate (62%). The probability of choosing triple therapy as initial treatment was further from 50% (the point of indifference) for more patients, making our prediction more confident, and suggesting a stronger recommendation could be made. After an inadequate response to methotrexate, the choice was more split, suggesting a decision aid may be helpful. CONCLUSION: Using a novel approach, we estimated that many patients with early rheumatoid arthritis may prefer triple therapy to other treatment options, in contrast to existing guidelines. This offers an approach that may help inform Grading of Recommendations Assessment, Development, and Evaluation treatment recommendations.
29882440 The add-on effectiveness and safety of iguratimod in patients with rheumatoid arthritis wh 2019 Jul Objectives: To evaluate the effectiveness of add-on iguratimod (IGU) in patients with rheumatoid arthritis (RA) who showed an inadequate response to tocilizumab (TCZ), especially patients who were intolerant of an effective dose of methotrexate (MTX). Methods: Thirty-one patients with RA (22 women, age 62.4 years, disease duration 13.8 years, prior TCZ duration 35.7 months, 25 intravenous [8 mg/kg/4 weeks] and 6 subcutaneous [162 mg/2 weeks] TCZ treatments, concomitant MTX 8.5 mg/week [35.5%], and prednisolone (PSL) 4.3 mg/day [25.8%]) who showed an inadequate response to TCZ (disease activity score assessing 28 joints with C-reactive protein [DAS28-CRP] 2.9, clinical disease activity index [CDAI] 15.0, 28 secondary inadequate responders) were treated with additional IGU (final dose 41.7 mg/day) and enrolled in this 24-week, multicenter, retrospective study. Results: Twenty-nine patients (93.5%) continued the treatment for 24 weeks (one dropped out for pneumonia and one for digestive symptoms). The TCZ and the concomitant dose and rate of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (MTX, salazosulfapyridine [SASP], and tacrolimus [TAC]) were not significantly changed during this period. Outcome measures improved significantly, as follows: DAS28-CRP from 2.9 to 1.7 (p < .001); CDAI from 15.0 to 6.0 (p < .001); modified Health Assessment Questionnaire (mHAQ) from 0.8 to 0.6 (p < .05); and rheumatoid factor (RF) from 382.1 to 240.3 IU/mL (p < .001). Using the EULAR criteria, 64.5% achieved a moderate response, and 51.6% achieved ACR 20 at 24 weeks. Conclusion: Adding IGU to inadequate responders to TCZ may be a promising and safe complementary treatment option.
30048527 Risk of autoimmune rheumatic diseases in patients with palindromic rheumatism: A nationwid 2018 OBJECTIVE: To estimate the relative risk of autoimmune rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren's syndrome (SS), dermatomyositis (DM) and polymyositis (PM), among patients with palindromic rheumatism (PR) compared with non-PR individuals. METHODS: The study utilized 2003-2013 claims data from the Taiwanese National Health Insurance Research Database. We identified 4,421 cases of PR from 2007 to 2012 and randomly chose 44,210 non-PR individuals who matched (1:10) for age, sex and the year of index date without prior history of RA, SLE, SSc, SS, DM, or PM. After adjusting for age, sex, and the Charlson comorbidity index, we calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard model to quantify the risk of RA, SLE, SS, DM and PM in PR patients compared with that in matched non-PR individuals. RESULTS: Among the 4,421 patients with PR, 569 (12.87%) developed RA, 269 (6.08%) developed SS, 113 (2.56%) developed SLE, 5 (0.11%) developed SSc, 8 (0.18%) developed PM, and 1 (0.02%) developed DM. After adjusting for potential confounders, the patients with PR had an increased risk of RA (HR, 118.76; 95% CI, 89.81-157.04), SS (HR, 59.57; 95% CI, 43.87-80.88), SLE (HR, 51.56; 95% CI, 32.96-80.66) PM (HR, 57.38; 95% CI, 6.90-476.83), and SSc (HR, 13.42; 95% CI, 3.79-47.55) but not of DM (HR, 3.44; 95% CI, 0.34-34.59). CONCLUSION: Patients with PR had an increased risk of developing RA, SS, SLE, PM, and SSc.
30576759 TNF-α inhibitor-induced psoriasis: A decade of experience at the Cleveland Clinic. 2020 Dec BACKGROUND: Tumor necrosis factor-α (TNF-α) inhibitor (TNFI)-induced psoriasis remains poorly understood despite having been described 15 years ago. As TNFIs often provide life-changing patient benefits, understanding effective treatments for TNFI-induced psoriasis is important. OBJECTIVE: We characterized a cohort of patients with TNFI-induced psoriasis whose psoriasis was specifically diagnosed and managed or comanaged by dermatologists at a single tertiary care institution over a 10-year period. METHODS: Retrospective review of patients in whom TNFI-induced psoriasis was diagnosed between 2003 and 2013. RESULTS: A total of 102 patients with TNFI-induced psoriasis were identified. The mean age of onset was 40 years, and there was a female predominance (73.5%). Crohn's disease (in 48% of cases) and rheumatoid arthritis (in 24.5% of cases) were the most common primary conditions. Infliximab (in 52% of cases) was the most common inciting agent. The most common TNFI-induced psoriasis subtypes were plaque-type psoriasis (49.5%), scalp psoriasis (47.5%), and palmoplantar pustulosis (41%). Topical medications alone improved or resolved TNFI-induced psoriasis in 63.5% of patients, and cyclosporine and methotrexate (>10 mg weekly) were often effective if topicals failed. Discontinuation of the inciting TNFI with or without other interventions improved or resolved TNFI-induced psoriasis in 67% of refractory cases, whereas switching TNFIs resulted in persistence or recurrence in 64%. LIMITATIONS: Retrospective nature of the study and the fact that some patients may have developed typical psoriasis unresponsive to TNFIs. CONCLUSION: Our study cohort represents the largest single-institution cohort of patients with TNFI-induced psoriasis diagnosed and managed or comanaged by dermatologists to date. On the basis of our findings, we propose a treatment algorithm for TNFI-induced psoriasis.
30498756 Increased Autophagy Enhances the Resistance to Tumor Necrosis Factor-Alpha Treatment in Rh 2018 Tumor Necrosis Factor-alpha (TNF-α) was reported to increase autophagy in rheumatoid arthritis human fibroblast-like synovial cell (RA-HFLS). We investigated different levels of TNF-α exposed to RA-HFLS by focusing on the relationship of autophagy and apoptosis. RA-HFLS and normal human fibroblast-like synovial cell (HFLS) were stimulated by TNF-α in the presence or the absence of 3-methyladenine (3-MA) or chloroquine (CQ). Cell apoptosis was detected by flow cytometry. Autophagy was determined through the expression levels of LC3, Beclin1, and P62 measured by Western Blot analysis as well as Confocal Laser Scanning Microscopy. The basal autophagy level was significantly higher in RA-HFLS than in HFLS. Autophagy was enhanced both in RA-HFLS and HFLS when they were treated with TNF-α. With the treatment of TNF-α, a slightly higher autophagy level was found in RA-HFLS than in HFLS, without a dose dependent effect. When autophagy was inhibited by 3-MA or CQ, apoptosis increased in both groups. With the stimulation of different doses TNF-α, apoptosis was much higher in HFLS group than in RA-HFLS. Autophagy is a protection mechanism when treated by TNF-α in RA-HFLS.
29664819 Risk Factors for Pneumocystis jirovecii Pneumonia in Patients With Rheumatoid Arthritis an 2018 Oct BACKGROUND/OBJECTIVES: Immunosuppressant medications (ISPs) increase the occurrence of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients. The prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) for PCP is effective but has serious adverse effects and so should be selectively used for patients at high risk. The aims of this study were to clarify the risk factors for PCP in RA patients and to establish the indications for administering TMP/SMX. METHODS: This retrospective cohort study analyzed data from 2640 patients (2010-2014) diagnosed as having RA who had not received a prophylactic administration of TMP/SMX. The risk factors for PCP were evaluated by comparing the clinical parameters between patients with PCP (PCP group, n = 19) and those without (non-PCP group, n = 2621). RESULTS: The PCP group was older (70 vs. 64 years), received higher doses of prednisolone (6.2 vs. 2.4 mg/d) and methotrexate (7.7 vs. 5.2 mg/wk), and had a greater number of ISPs (1.3 vs. 0.8) (p < 0.05). We stratified the PCP risk using a scoring system based on odds ratios (ORs) calculated for these parameters (methotrexate ≥6 mg/wk OR = 4.5, 1 point; age ≥65 years, OR = 3.7, 1 point; ≥2 ISPs, OR = 3.7, 1 point; prednisolone ≥5 mg/d, OR = 12.4, 3 points). The incidence of PCP among patients scoring 0 to 2 points was 0.04%; 3 to 4 points, 2.3%; and 5 points or more, 5.8%. CONCLUSIONS: The prophylactic administration of TMP/SMX for PCP is recommended for RA patients who score at least 5 points with our system.
28850026 Interleukin-35 inhibits angiogenesis through STAT1 signalling in rheumatoid synoviocytes. 2018 Mar OBJECTIVES: We studied the anti-angiogenic effect of interleukin-35 (IL-35) by investigating its effects on signal transmission through the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway in fibroblast-like synoviocytes (FLS). METHODS: Using the collagen-induced arthritis (CIA) model of rheumatoid arthritis (RA), we derived and cultured FLS, stimulated FLS with IL-35 at different concentrations and examined the expression levels of mRNA and protein of both vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), endostatin, TNF-α, and IL-6 using reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting. We used Western blotting to study the effects of IL-35 on the function of the JAK-STAT pathway in FLS. RESULTS: IL-35 treatment inhibited the expression of VEGF, FGF-2, TNF-α and IL-6, and increased the expression of endostatin in FLS. Western blotting showed that IL-35 treatment of CIA-derived FLS resulted in signalling through STAT1, but not through STAT3 or STAT5. CONCLUSIONS: IL-35 signalling through STAT1 and inhibition of the expression of mediators of angiogenesis and inflammation in FLS provide a likely mechanism for anti-angiogenic effects seen in experimental models of RA. Our data suggest that IL-35 and its signalling pathway represent a therapeutic target for the treatment of RA and other angiogenesis-related diseases.
29040451 An omnibus test for differential distribution analysis of microbiome sequencing data. 2018 Feb 15 MOTIVATION: One objective of human microbiome studies is to identify differentially abundant microbes across biological conditions. Previous statistical methods focus on detecting the shift in the abundance and/or prevalence of the microbes and treat the dispersion (spread of the data) as a nuisance. These methods also assume that the dispersion is the same across conditions, an assumption which may not hold in presence of sample heterogeneity. Moreover, the widespread outliers in the microbiome sequencing data make existing parametric models not overly robust. Therefore, a robust and powerful method that allows covariate-dependent dispersion and addresses outliers is still needed for differential abundance analysis. RESULTS: We introduce a novel test for differential distribution analysis of microbiome sequencing data by jointly testing the abundance, prevalence and dispersion. The test is built on a zero-inflated negative binomial regression model and winsorized count data to account for zero-inflation and outliers. Using simulated data and real microbiome sequencing datasets, we show that our test is robust across various biological conditions and overall more powerful than previous methods. AVAILABILITY AND IMPLEMENTATION: R package is available at https://github.com/jchen1981/MicrobiomeDDA. CONTACT: chen.jun2@mayo.edu or zhiwei@njit.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
30529106 Effect of lentivirus-mediated overexpression or silencing of MnSOD on apoptosis of resvera 2019 Feb 5 Fibroblast-like synoviocytes in rheumatoid arthritis (RA-FLSs) play a key role in cartilage destruction. We previously found that resveratrol (Res) could promote FLSs apoptosis in adjuvant arthritis rats, but the underlying mechanism was unclear. According to our latest study, Res can suppress the expression of mitochondrial superoxide dismutase (MnSOD) and RA-FLSs proliferation. It was associated with elevated mitochondrial reactive oxygen species levels. Therefore, we hypothesized that Res-mediated RA-FLSs apoptosis might occur via the MnSOD- mitochondrial reactive oxygen species pathway. RA-FLSs were infected with lentiviruses and screened with puromycin at a concentration of 8 µg/ml. We divided the RA-FLSs into four groups: a control group, a negative control (NC) group, a MnSOD overexpression group, and a MnSOD RNAi group. The four groups of RA-FLSs were tested using confocal laser scanning microscopy, CCK-8 assays, flow cytometry, and western blotting were conducted to determine the involvement of the MnSOD-mitochondrial reactive oxygen species pathway. Compared with the NC group, the MnSOD overexpression group treated with different concentrations of Res (0, 25, 50, 100, or 200 μM) and 5 μM H(2)O(2) showed reduced levels of mitochondrial reactive oxygen species, increased B-cell-lymphoma-2 (Bcl-2), reduced Bcl-2 Associated X protein (Bax), and fewer apoptotic cells. The MnSOD RNAi group showed the opposite results. Thus, we concluded that Res could facilitate RA-FLSs apoptosis by regulating MnSOD expression and mitochondrial reactive oxygen species levels. Our findings show a novel mechanism for the beneficial effects of Res, especially in relation to the MnSOD-mitochondrial reactive oxygen species signaling pathway in RA.
29307092 Health-related quality of life outcomes in patients with rheumatoid arthritis and ankylosi 2018 Feb Treatment with biological disease-modifying anti-rheumatic drugs (bDMARDs) for rheumatoid arthritis (RA) and ankylosing spondylitis (AS) is popular. The aim of this study was to investigate changes in the quality of life (QoL) in patients after receiving, tapering, or stopping bDMARD treatment. Three hundred and thirty patients with RA and 120 patients with AS were enrolled. Data on the patients receiving bDMARDs were obtained by self-completed questionnaires including the short-form 36 (SF-36) and Global Quality of Life (GQL) scale. A relapse was defined as the QoL becoming worse than that before bDMARD treatment. Significant improvement in all domains of the SF-36 and GQL was noted in the patients after receiving bDMARDs. Improvement in SF-36 was significantly greater in RA patients with a shorter disease duration (< 6 years) and milder patient-assessed disease activity and in AS patients with a shorter disease duration and younger age. There were significant decreases in all domains of the SF-36 and GQL in both groups after reducing/discontinuing bDMARD treatment. The patients in both groups with a shorter period of bDMARD treatment (≤ 3 years) had significantly worse SF-36 scores compared to those with a longer period of bDMARD treatment (> 3 years). The relapse rate after reducing/discontinuing treatment was over 90.0% in the RA patients and over 50.0% in the AS patients within 12 months. bDMARDs significantly improved the QoL of the patients with RA and AS. However, interrupting or stopping the treatment protocol worsened the QoL and led to relapses, especially in the patients who used bDMARDs for a shorter period.
29236318 Proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes following 2019 Mar OBJECTIVE: In this study, we investigated the effects of delivering small interfering RNA (siRNA) for efficient STAT3 downregulation on propagation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). METHODS: The FLSs were transfected with three different siRNAs. RNAi-1 was selected for further experiments. The expression levels of both STAT3 messenger RNA (mRNA) and its protein were detected by a real-time polymerase chain reaction and Western blot analysis. The proliferation of FLSs was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The apoptosis of FLSs was examined by flow cytometry. The expression levels of cell apoptotic-related genes Bcl-2, Bax, and caspase-3 were detected by Western blot analysis. RESULTS: RNAi-1 was selected as the RNAi group for its lowest expression levels of STAT3 mRNA. In RNAi group, the proliferation of synoviocytes was much lower and the apoptosis rate was significantly higher. FLSs of RNAi-1 group showed significantly lower expression level of apoptotic-inhibiting gene Bcl-2 and significantly higher expression levels of proapoptotic gene Bax and apoptotic protease caspase-3. CONCLUSION: Transfection with targeted STAT3 recombinant plasmids effectively inhibited the expression of STAT3 mRNA and its protein in RA-FLSs. RNAi-mediated silencing of STAT3 reduced the proliferation and promoted the apoptosis of FLSs.
30268016 Plasma interleukin-38 in patients with rheumatoid arthritis. 2018 Dec Previous studies have indicated that interleukin-38 (IL-38) is involved in rheumatoid arthritis (RA). The present study aims to assess plasma levels of IL-38 in RA and discuss the potential of IL-38 as a biomarker for RA. Protein concentrations of IL-38 were examined by enzyme-linked immunosorbent assay, and the mRNA level of IL-38 was tested by quantitative real-time polymerase chain reaction. Plasma IL-38 was first compared in a training cohort, including 130 RA patients and 53 healthy controls, given the optimal cutoff. Then, we validated the levels of IL-38 in a further cohort of 519 patients, including 250 with RA, 63 systemic lupus erythematosus, 62 primary Sjogren's syndrome, 51 gout, 63 osteoarthritis, and 30 psoriatic arthritis, as well as 60 healthy controls. To further discuss the changes in IL-38 after treatment and the relationship with disease activity, we tested IL-38 expression in RA patients from the training cohort under follow-up. In the training cohort, plasma levels of IL-38 were higher in RA patients compared with healthy controls (681.00 [234.45-826.47] versus 152.04 [70.06-246.80] pg/mL, P < 0.001). The IL-38 mRNA level was elevated in RA patients as compared with healthy controls (P < 0.001). Expression of IL-38 was significantly higher in RA patients compared with that in non-RA patients in the validation cohort (all P < 0.001). Treatment significantly reduced IL-38 expression. IL-38 expression was related to parameters of inflammation both at baseline and in the follow-up studies. The area under the curve (AUC) of the receiver-operating characteristic curve showed that IL-38 may be a potential biomarker for RA. At the optimal cutoff value of 341.90 pg/mL, the sensitivity, specificity, and AUC were 72.30%, 90.60%, and 0.840, respectively, in the training cohort. Similar results were noted in the validation cohort. In conclusion, IL-38 expression correlated with RA disease activity, and plasma IL-38 might be a promising diagnostic biomarker for RA.
30063798 Exercise for rheumatoid arthritis of the hand. 2018 Jul 31 BACKGROUND: Rheumatoid arthritis is an inflammatory polyarthritis that frequently affects the hands and wrists. Hand exercises are prescribed to improve mobility and strength, and thereby hand function. OBJECTIVES: To determine the benefits and harms of hand exercise in adults with rheumatoid arthritis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), MEDLINE, Embase, CINAHL, AMED, Physiotherapy Evidence Database (PEDro), OTseeker, Web of Science, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to July 2017. SELECTION CRITERIA: We considered all randomised or quasi-randomised controlled trials that compared hand exercise with any non-exercise therapy. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as outlined by the Cochrane Musculoskeletal Group. MAIN RESULTS: We included seven studies involving 841 people (aged 20 to 94 years) in the review. Most studies used validated diagnostic criteria and involved home programmes.Very low-quality evidence (due to risk of bias and imprecision) from one study indicated uncertainty about whether exercise improves hand function in the short term (< 3 months). On a 0 to 80 points hand function test (higher scores mean better function), the exercise group (n = 11) scored 76.1 points and control group (n = 13) scored 75 points.Moderate-quality evidence (due to risk of bias) from one study indicated that exercise compared to usual care probably slightly improves hand function (mean difference (MD) 4.5, 95% confidence interval (CI) 1.58 to 7.42; n = 449) in the medium term (3 to 11 months) and in the long term (12 months or beyond) (MD 4.3, 95% CI 0.86 to 7.74; n = 438). The absolute change on a 0-to-100 hand function scale (higher scores mean better function) and number needed to treat for an additional beneficial outcome (NNTB) were 5% (95% CI 2% to 7%); 8 (95% CI 5 to 20) and 4% (95% CI 1% to 8%); 9 (95% CI 6 to 27), respectively. A 4% to 5% improvement indicates a minimal clinical benefit.Very low-quality evidence (due to risk of bias and imprecision) from two studies indicated uncertainty about whether exercise compared to no treatment improved pain (MD -27.98, 95% CI -48.93 to -7.03; n = 124) in the short term. The absolute change on a 0-to-100-millimetre scale (higher scores mean more pain) was -28% (95% CI -49% to -7%) and NNTB 2 (95% CI 2 to 11).Moderate-quality evidence (due to risk of bias) from one study indicated that there is probably little or no difference between exercise and usual care on pain in the medium (MD -2.8, 95% CI - 6.96 to 1.36; n = 445) and long term (MD -3.7, 95% CI -8.1 to 0.7; n = 437). On a 0-to-100 scale, the absolute changes were -3% (95% CI -7% to 2%) and -4% (95% CI -8% to 1%), respectively.Very low-quality evidence (due to risk of bias and imprecision) from three studies (n = 141) indicated uncertainty about whether exercise compared to no treatment improved grip strength in the short term. The standardised mean difference for the left hand was 0.44 (95% CI 0.11 to 0.78), re-expressed as 3.5 kg (95% CI 0.87 to 6.1); and for the right hand 0.46 (95% CI 0.13 to 0.8), re-expressed as 4 kg (95% CI 1.13 to 7).High-quality evidence from one study showed that exercise compared to usual care has little or no benefit on mean grip strength (in kg) of both hands in the medium term (MD 1.4, 95% CI -0.27 to 3.07; n = 400), relative change 11% (95% CI -2% to 13%); and in the long term (MD 1.2, 95% CI -0.62 to 3.02; n = 355), relative change 9% (95% CI -5% to 23%).Very low-quality evidence (due to risk of bias and imprecision) from two studies (n = 120) indicated uncertainty about whether exercise compared to no treatment improved pinch strength (in kg) in the short term. The MD and relative change for the left and right hands were 0.51 (95% CI 0.13 to 0.9) and 44% (95% CI 11% to 78%); and 0.82 (95% CI 0.43 to 1.21) and 68% (95% CI 36% to 101%).High-quality evidence from one study showed that exercise compared to usual care has little or no benefit on mean pinch strength of both hands in the medium (MD 0.3, 95% CI -0.14 to 0.74; n = 396) and long term (MD 0.4, 95% CI -0.08 to 0.88; n = 351). The relative changes were 8% (95% CI -4% to 19%) and 10% (95% CI -2% to 22%).No study evaluated the American College of Rheumatology 50 criteria.Moderate-quality evidence (due to risk of bias) from one study indicated that people who also received exercise with strategies for adherence were probably more adherent than those who received routine care alone in the medium term (risk ratio 1.31, 95% CI 1.15 to 1.48; n = 438) and NNTB 6 (95% CI 4 to 10). In the long term, the risk ratio was 1.09 (95% CI 0.93 to 1.28; n = 422).Moderate-quality evidence (due to risk of bias) from one study (n = 246) indicated no adverse events with exercising. The other six studies did not report adverse events. AUTHORS' CONCLUSIONS: It is uncertain whether exercise improves hand function or pain in the short term. It probably slightly improves function but has little or no difference on pain in the medium and long term. It is uncertain whether exercise improves grip and pinch strength in the short term, and probably has little or no difference in the medium and long term. The ACR50 response is unknown. People who received exercise with adherence strategies were probably more adherent in the medium term than who did not receive exercise, but with little or no difference in the long term. Hand exercise probably does not lead to adverse events. Future research should consider hand and wrist function as their primary outcome, describe exercise following the TIDieR guidelines, and evaluate behavioural strategies.