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ID PMID Title PublicationDate abstract
28442886 Hydroxychloroquine for treatment of rheumatoid arthritis: multifocal electroretinogram and 2017 PURPOSE: To evaluate early changes in multifocal electroretinogram (mfERG) and subclinical aqueous humor flare and cellularity in patients receiving hydroxychloroquine (HCQ) as treatment for rheumatoid arthritis. METHODS: Ten patients receiving treatment with HCQ and no ophthalmic symptoms were enrolled. After complete ocular examination, mfERG and laser flare-cell photometry were performed. Patients were also divided into two subgroups with HCQ cumulative dose (CD) higher or lower than 500 g. Results obtained were compared with a control group of ten healthy subjects and statistical analysis was performed. RESULTS: In patients receiving HCQ treatment, mfERG P1-wave in ring 2 showed a significant reduction in amplitude and a significant increase in latency compared to healthy control subjects, respectively resulting in 1.143 μV vs 1.316 μV (P=0.040) and 38.611 ms vs 36.334 ms (P=0.024). These changes are highly related to CD. Furthermore, when using the laser flare-cell photometry, a significant increase in aqueous humor flare and cellularity was shown in patients with CD higher than 500 g, resulting in a mean value of 14.4 ph/ms compared to 8.1 ph/ms in patients with CD lower than 500 g (P=0.0029). These reports appear highly related to CD (P=0.001). Receiver operating characteristic curve analysis showed mfERG P1-wave amplitude in ring 2 as the most sensitive value in detecting early HCQ-related retinopathy. CONCLUSION: MfERG was shown to be a very sensitive test in detecting early retinal toxicity and should be used for the screening of patients receiving HCQ treatment. Although less sensitive, laser flare-cell photometry can provide further information to evaluate early toxic retinal cell damage.
28392862 Role of LncRNA-AF085935, IL-10 and IL-17 in Rheumatoid Arthritis Patients With Chronic Hep 2017 May BACKGROUND: The current study aimed at testing the effect of corticosteroid therapy on serum levels of interleukin-10 (IL-10) and IL-17 as well as lncRNA-AF085935 in patients of rheumatoid arthritis (RA) associated with hepatitis C virus (HCV) and evaluating the usefulness of using these parameters to predict the therapeutic efficacy of steroids in these patients. METHODS: Thirty healthy control subjects and 65 chronic HCV patients with RA were included in our study. Patients were subjected to clinical examination, abdominal ultrasound, and liver biopsy and received 6-methyl-prednisolone (PDN) 16 mg/day for 48 weeks. Blood samples were collected from all subjects and serum was separated to assess IL-10 and IL-17 by ELISA and HCV RNA and lncRNA-AF085935 by qRT-PCR. RESULTS: Our study revealed that there were significant increases in serum levels of IL-10, IL-17 and lncRNA-AF085935 in RA patients associated with HCV compared with healthy control subjects. Also there were significant increases in serum levels of IL-10 and HCV RNA and a significant decrease in serum level of IL-17 in patients after corticosteroid therapy, while lncRNA-AF085935 is not significantly changed. CONCLUSION: LncRNA-AF085935 might be a useful candidate biomarker for the early detection of RA associated with HCV, providing potential new strategies for early screening and therapy of these patients. IL-17 is a non-invasive prognostic marker to predict the efficacy of corticosteroid therapy in RA patients associated with chronic hepatitis C.
30375543 Anti-Citrullinated Cyclic Peptide Antibody and Functional Disability Are Associated With P 2017 Mar OBJECTIVES: This study aims to determine the predictors of poor sleep quality in rheumatoid arthritis (RA). PATIENTS AND METHODS: This was a monocentric, cross sectional, case-control study which was conducted at the Putrajaya Hospital, Malaysia. We recruited 46 patients with RA (3 males; 43 females; mean age 48.15±14.96) and 46 age and sex-matched healthy controls (3 males; 43 females; mean age 47.11±12.22). RA patients were assessed for their disease activity based on disease activity score in 28 joints, disease damage based on radiographic erosions, and functional status based on Health Assessment Questionnaire Disability Index. The Pittsburgh Sleep Quality Index (PSQI) scores were determined by interviewing all the subjects. Subjects with RA were further subdivided based on their PSQI scores as "good sleepers" with PSQI scores of <5 and "poor sleepers" with PSQI scores of ≥5. RESULTS: The percentage of poor sleepers was significantly higher among RA patients (47.83% versus 9.57%). Median scores of 5 out of 7 components of the PSQI were higher among RA patients compared to controls. Among poor sleepers with RA, a significantly higher proportion tested positive for anti-citrullinated cyclic peptide autoantibodies (p=0.037). Besides, poor sleepers had significantly higher median Health Assessment Questionnaire Disability Index (p=0.017) than good sleepers. However, both Health Assessment Questionnaire Disability Index (p=0.968) and anti-citrullinated cyclic peptide (p=0.431) were insignificant when entered in the equation of a logistic regression model. CONCLUSION: The findings of this study demonstrate a link between functional disability, anti-citrullinated cyclic peptide antibodies, and sleep quality in RA.
28881836 The prevalence of depression in rheumatoid arthritis in China: A systematic review. 2017 Aug 8 This systematic review is to explore the prevalence of depression in patients with rheumatoid arthritis (RA) in China. Articles of prevalence rates for depression in adult RA patients published before October 2015 were identified from PubMed, Embase, The Cochrane Library, CNKI, CBM, VIP, and Wanfang database and other internet databases. Relevant journals and the recommendations of expert panels were also searched manually. Two independent reviewers searched and assessed the literature. Therelevant data were applied with Meta-Analyst 3.13 software, and the forest plot and funnel plot were performed. 21 studies with a total of 4447 patients were selected to be enrolled in this study. The prevalence of depression by analyzing the effect size was 48% [95% CI (41%, 56%)]. The prevalence of minor depression and dysthymic disorder was 30% [95%CI (23%, 38%)], and the moderate or major depression was 18% [95%CI (11%, 29%)], respectively. Subgroup analysis showed that the depression rate of female RA patients was higher than male. The depression rate in the central and western areas were higher than that of the eastern region of China, the prevalence level estimated by the Geriatric Depression Scale (GDS) was higher than estimated by other tools. Sensitivity analysis showed that the pooled effect size had good stability and reliability, To be conclusive, the prevalence rate of depression in RA patients is 48%, which suggesting that medical staff should pay more attention to depression in adult patients with RA.
30207575 Passive Smoking is Responsible for Disease Activity in Female Patients With Rheumatoid Art 2018 Jun OBJECTIVES: This study aims to evaluate the effects of passive smoking on disease activity in female patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: Among a total of 191 female patients with RA (mean age 59.1±12.5 years; range 21 to 87 years) consecutively recruited, 100 female patients (mean age 56.1±13.4 years; range 21 to 87 years) completed the study with mean 17.3 months of follow-up. Patients were classified according to smoking status: current, never, passive, or ex-smoker. Clinical response between never and passive smokers was assessed by disease- activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (DAS28-ESR and DAS28-CRP) and by the European League Against Rheumatism response criteria. RESULTS: Among the 100 female RA patients analyzed, the distribution of smoking status was as follows: current (n=3), never (n=55), passive (n=34), and ex-smokers (n=8). There was no difference of DAS28-ESR and DAS28-CRP between never and passive smokers at baseline. At the time of follow-up, the values of DAS28-ESR and DAS28-CRP in never smokers were significantly decreased than those in passive smokers (p=0.019 and p=0.023, respectively). Patients who never smoked showed a trend to have good or moderate European League Against Rheumatism response without statistical significance, compared to passive smokers (52.7% vs. 32.4%, respectively; p=0.060). CONCLUSION: This preliminary study implicates that passive smoking might be responsible for higher disease activity in female RA patients and never smoking might induce good clinical response in RA.
29900969 High Disease Activity May Increase Fear-Avoidance Beliefs in Rheumatoid Arthritis. 2017 Dec OBJECTIVES: This study aims to compare fear-avoidance (FA) beliefs of rheumatoid arthritis (RA) patients with osteoarthritis (OA) of hand patients and fibromyalgia (FM) patients and evaluate its relationship with RA activity and duration. PATIENTS AND METHODS: The study included 206 patients with RA (34 males, 172 females; mean age 49 years; range 20 to 72 years), 57 patients with FM (57 females; mean age 48 years; range 20 to 71 years), and 50 patients with OA of hand (4 males, 46 females; mean age 43 years; range 43 to 77 years). FA beliefs were assessed with modified Fear-Avoidance Belief Questionnaire (mFABQ). RA patients were dichotomized according to disease activity and disease duration separately; cutoff values were disease activity score 28 of 3.2 and six months of disease activity, respectively. RESULTS: Modified Fear-Avoidance Belief Questionnaire scores were similar in patients with RA, OA of hand, and FM. RA patients in non-remission group had higher mFABQ scores. Moreover, mFABQ scores were similar in RA patients with early and established disease groups. CONCLUSION: Fear-avoidance beliefs of patients with RA were similar with OA of hand patients and FM patients. However, higher disease activity in RA was related with escalated FA beliefs. Further studies focusing on pathophysiology of FA beliefs in patients with RA are warranted for effective pain management of RA.
30375535 Presarcopenia and its Impact on Disability in Female Patients With Rheumatoid Arthritis. 2017 Mar OBJECTIVES: This cross-sectional pilot study aims to investigate presarcopenia in female patients with rheumatoid arthritis (RA) and to evaluate its relationship to the disability assessment. PATIENTS AND METHODS: Forty female patients with RA (mean age 48.29±8.34; range 31 to 66 years) and 40 healthy controls (mean age 46.21±6.90; range 31 to 58 years) matched for age, sex, and body mass index were included. Pain, morning stiffness duration, disease activity score, erythrocyte sedimentation rate, C-reactive protein, and Health Assessment Questionnaire (HAQ) were evaluated. Body compositions were assessed with whole body dual energy X-ray absorptiometry. The appendicular skeletal muscle mass and skeletal muscle mass index (SMI) of RA patients were compared to the controls and possible correlations between SMI, disease characteristics, and HAQ score were investigated. RESULTS: The body mass index values and percentages of obese, overweight, and healthy weight subjects were similar in the patient and control groups. However, appendicular skeletal muscle mass and SMI calculations were significantly lower, and the percentage of presarcopenia was significantly higher in patients with RA (20%) than controls (7%) (p<0.05). Although there was no significant correlation between SMI and other parameters, a significant negative correlation was determined between SMI and HAQ score in patients with RA (p<0.05). CONCLUSION: We demonstrated lower SMI values and higher presarcopenia ratios in patients with RA than healthy controls. Independent from other disease characteristics, the inverse correlation between SMI and HAQ scores may contribute to understanding of the impact of the process on patient disability.
27412602 Update on Pathogenesis of Sjogren's Syndrome. 2017 Sjogren's syndrome is a common autoimmune disease that presents with sicca symptoms and extraglandular features. Sjogren's syndrome is presumably as common as RA; yet it is poorly understood, underdiagnosed and undertreated. From the usual identity as an autoimmune exocrinopathy to its most recent designate as an autoimmune epithelitis - the journey of SS is complex. We herein review some of the most important milestones that have shed light on different aspects of pathogenesis of this enigmatic disease. This includes role of salivary gland epithelial cells, and their interaction with cells of the innate and adaptive immune system. Non-immune factors acting in concert or in parallel with immune factors may also be important. The risk genes identified so far have only weak association, nevertheless advances in genetics have enhanced understanding of disease mechanisms. Role of epigenetic and environmental role factors is also being explored. SS has also some unique features such as congenital heart block and high incidence of lymphoma; disease mechanisms accounting for these manifestations are also reviewed.
28974912 Cardiovascular comorbidities of rheumatoid arthritis in Taiwanese adults: A retrospective 2017 Jul OBJECTIVE: To evaluate the association between rheumatoid arthritis (RA) and cardiovascular comorbidities, including hyperlipidemia, hypertension, and diabetes, in Taiwanese patients based on the data from medical records. MATERIALS AND METHODS: A retrospective study was performed using the computerized medical records from a regional hospital located in southern Taiwan. A total of 2293 patients (age range 30-79 years) with a diagnosis of RA (International Classification of Diseases, Ninth Revision, Clinical Modification code 714.0) treated since the opening of the study hospital in July 2000 until February 2013 were included. The RA cases were frequency matched for age and sex with 9172 patients without RA. The associations of RA with hyperlipidemia, hypertension, and diabetes were evaluated using multiple logistic regression analysis. RESULTS: Significant associations between RA and hyperlipidemia (adjusted odds ratio [OR] = 2.05, 95% confidence interval [CI] = 1.77-2.38, P < 0.001) and hypertension (adjusted OR = 2.76, 95% CI = 2.43-3.14, P < 0.001) were observed. However, diabetes was not significantly associated with RA in either male or female patients. CONCLUSION: Findings from this retrospective medical record study indicated that hyperlipidemia and hypertension were significant cardiovascular comorbidities of RA.
28316886 Identification of dysregulated genes in rheumatoid arthritis based on bioinformatics analy 2017 BACKGROUND: Rheumatoid arthritis (RA) is a chronic auto-inflammatory disorder of joints. The present study aimed to identify the key genes in RA for better understanding the underlying mechanisms of RA. METHODS: The integrated analysis of expression profiling was conducted to identify differentially expressed genes (DEGs) in RA. Moreover, functional annotation, protein-protein interaction (PPI) network and transcription factor (TF) regulatory network construction were applied for exploring the potential biological roles of DEGs in RA. In addition, the expression level of identified candidate DEGs was preliminarily detected in peripheral blood cells of RA patients in the GSE17755 dataset. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to validate the expression levels of identified DEGs in RA. RESULTS: A total of 378 DEGs, including 202 up- and 176 down-regulated genes, were identified in synovial tissues of RA patients compared with healthy controls. DEGs were significantly enriched in axon guidance, RNA transport and MAPK signaling pathway. RBFOX2, LCK and SERBP1 were the hub proteins in the PPI network. In the TF-target gene network, RBFOX2, POU6F1, WIPF1 and PFKFB3 had the high connectivity with TFs. The expression status of 11 candidate DEGs was detected in GSE17755, the expression levels of MAT2A and NSA2 were significantly down-regulated and CD47 had the up-regulated tendency in peripheral blood cells of patients with RA compared with healthy individuals. qRT-PCR results of MAT2A, NSA2, CD47 were compatible with our bioinformatics analyses. DISCUSSION: Our study might provide valuable information for exploring the pathogenesis mechanism of RA and identifying the potential biomarkers for RA diagnosis.
28163961 The adjuvant use of calcium fructoborate and borax with etanercept in patients with rheuma 2017 Jan OBJECTIVE: This study was designed to evaluate the effects calcium fructoborate (CFB) and sodium tetraborate (NTB) as supplements in Iraqi patients with active rheumatoid arthritis (RA) maintained on etanercept. MATERIALS AND METHODS: A double-blind randomized placebo-controlled clinical trial with 60 days treatment period was carried out at Baghdad Teaching Hospital, Medical city, Baghdad, Iraq. Eighty RA patients were randomized into three groups to receive either 220 mg/day CFB, 55 mg/day NTB in capsule dosage form (equivalent to 6 mg elemental Boron), or placebo formula once daily. Only 72 patients completed the study. All patients were clinically evaluated utilizing DAS28-erythrocyte sedimentation rate (ESR), simple disease activity index-C-reactive protein (CRP), and clinical disease activity index scores at baseline, and at the end of the study. Venous blood was obtained at baseline and after 60 days, and utilized for the measurement of ESR, hemoglobin, in addition to evaluation of high-sensitivity CRP (hsCRP), tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and IL-6. RESULTS: After 60 days, both types of boron significantly improve the clinical scores, in association with significant decrease in the serum levels of ESR, hsCRP, IL-1α, IL-6, and TNF-α with remarkable superiority for calcium fructoborate (CFB) over sodium tetraborate (NTB), compared to baseline and placebo-treated group. CONCLUSION: The use of boron, as adjuvant with etanercept, has potentiated therapeutic outcomes in RA patients, and may be a new strategy to improve treatment, and avoid the problems associated with biologics utilized in RA treatment.
29332960 Nutrition and quality of life referring to physical abilities - a comparative analysis of 2017 OBJECTIVES: A comparative analysis of opinions on diet and nutrition of patients suffering from rheumatoid arthritis (RA) and osteoarthritis (OA), and quality of life limited to physical abilities in both study groups. MATERIAL AND METHODS: In the period from August to December 2012 an anonymous questionnaire survey was carried out among the patients of the Institute of Rheumatology. The respondents were asked to define their dietary preferences, dietary supplementation, and the level of physical limitations by completing the Health Assessment Questionnaire (HAQ). The study was carried out with the consent of the Bioethics Committee. RESULTS: A total of 397 questionnaires were obtained. The majority of respondents were women (77%). 62% of RA patients (165 respondents) had been treated for over 10 years as opposed to OA patients (80 respondents), where the largest group (33%) were patients during their first year. There is a significant difference in the disability level of patients in both compared groups. The average HAQ of RA patients was 1.09 and OA patients - 0.46. A change of dietary habits was declared by 32% of RA patients and by 17% of OA patients (p = 0.049) mostly without consulting a specialist - it concerned mainly limiting the consumption of sweets (30% vs. 21%), a meatless diet: 19% vs. 14%, and a non-dairy diet: 9% vs. 14%. CONCLUSIONS: Regardless of their diagnosis, the respondents believe that the way of eating affects their health. There are visible differences between diet and dietary supplementation, depending on the diagnosis of the disease. Differences were also observed in physical limitations of both patient groups - a higher level of disability was noted among RA patients. It is necessary to continue the topic at the level of clinical trials and medical experiments within the scope of the impact of diet as a supportive element in the treatment of rheumatic diseases.
29290847 Predictor of the Simplified Disease Activity Index 50 (SDAI 50) at Month 3 of bDMARD Treat 2017 OBJECTIVES: The Simplified Disease Activity Index (SDAI) 50 has good agreement with European League Against Rheumatism (EULAR) response measures for early Rheumatoid Arthritis (RA). There have been reports on early RA, but not on long-established RA. In this study, we analysed the relationships between various baseline factors and SDAI 50 after three months of treatment with biological disease-modifying antirheumatic drugs (bDMARDs) to determine the prognostic factors for long-established RA. METHODS: Subjects were 260 RA patients who had been treated with bDMARDs for 3 months. The following characteristics were investigated: Patient backgrounds, the erythrocyte sedimentation rate (ESR), C-reactive protein and serum matrix metalloproteinase-3 levels, SDAI scores, and health assessment questionnaire disability index and short form-36 scores. As a primary outcome index, the SDAI response was defined as a 50% reduction in the SDAI score between baseline and 3 months (SDAI 50). RESULTS: Baseline values of disease duration (odds ratio: 0.942, 95% CI: 0.902-0.984), smoking history (odds ratio: 2.272, 1.064-4.850), 28-tender joint count (odds ratio: 0.899, 0.827-0.977), evaluator's global assessment (odds ratio: 1.029, 1.012-1.047) and ESR (odds ratio: 1.015, 1.001-1.030) were determined to be significant factors based on logistic regression analysis. CONCLUSION: Our study demonstrated that RA patients with shorter disease duration, no smoking, and higher RA disease activity are more likely to achieve SDAI 50 through bDMARD treatment.
28831712 Treatment with Biologicals in Rheumatoid Arthritis: An Overview. 2017 Dec Management and therapy of rheumatoid arthritis (RA) has been revolutionized by the development and approval of the first biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumor necrosis factor (TNF) α at the end of the last century. Today, numerous efficacious agents with different modes of action are available and achievement of clinical remission or, at least, low disease activity is the target of therapy. Early therapeutic interventions aiming at a defined goal of therapy (treat to target) are supposed to halt inflammation, improving symptoms and signs, and preserving structural integrity of the joints in RA. Up to now, bDMARDs approved for therapy in RA include agents with five different modes of action: TNF inhibition, T cell co-stimulation blockade, IL-6 receptor inhibition, B cell depletion, and interleukin 1 inhibition. Furthermore, targeted synthetic DMARDs (tsDMARDs) inhibiting Janus kinase (JAK) and biosimilars also are approved for RA. The present review focuses on bDMARDs and tsDMARDS regarding similarities and possible drug-specific advantages in the treatment of RA. Furthermore, compounds not yet approved in RA and biosimilars are discussed. Following the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) recommendations, specific treatment of the disease will be discussed with respect to safety and efficacy. In particular, we discuss the question of favoring specific bDMARDs or tsDMARDs in the two settings of insufficient response to methotrexate and to the first bDMARD, respectively.
28243967 Evaluation of Usability and Acceptance of a New Autoinjector Intended for Methotrexate Sub 2017 Jun INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, for which the introduction of injectable treatments has had a major impact on quality of life directly related to the disease. The purpose of this descriptive study was to evaluate the usability of a new autoinjector, intended for methotrexate self-administration, based on the device's design and instructions for use (IFU). METHODS: This multicenter trial included three user groups: a group of patients with established RA subdivided into two groups according to their hand disability, and a group of caregivers or nurses. Each subject performed three simulated injections with a water-filled device on a foam pad. The first injection was made just after reading the IFU without further instructions (first phase). The second phase consisted of two injections made after explanations provided upon request of the subject in an optimum environment and in a "worst-case" home environment. The usability of the autoinjector was assessed by a questionnaire (success: ≥75% of positive responses) and by a score card reflecting injection performances (success: execution of ≥75% of handling steps). RESULTS: Forty-two subjects were enrolled in the study. During the first phase, the great majority of subjects succeeded in the usability questionnaire (90.5%) and in the injection performance (95.2%) with no major differences between the user groups. In the Second phase, all subjects from all three user groups succeeded in the usability questionnaire and had a positive rate of device handling, regardless of the environment and of the user group. No safety concerns were raised during the study. CONCLUSIONS: This study found a very high level of usability and subject acceptance of the autoinjector, intended for methotrexate self-administration, regardless of the hand disability and environmental conditions. FUNDING: Nordic Group. TRIAL REGISTRATION: EudraCT reference number: 2014-A0141245.
28588495 A Brief History of IL-1 and IL-1 Ra in Rheumatology. 2017 The history of what, in 1979, was called interleukin-1 (IL-1), orchestrator of leukocyte inter-communication, began many years before then, initially by the observation of fever induction via the endogenous pyrogen (EP) (1974) and then in rheumatology on the role in tissue destruction in rheumatoid diseases via the induction of collagenase and PGE(2) in human synovial cells by a mononuclear cell factor (MCF) (1977). Since then, the family has exploded to presently 11 members as well as many membrane-bound and soluble receptor forms. The discovery of a natural Interleukin-1 receptor antagonist (IL-1Ra) in human biological fluids has highlighted the importance of IL-1 and IL-1Ra in human diseases. Evidence delineating its role in autoinflammatory syndromes and the elucidation of the macromolecular complex referred to as "inflammasome" have been instrumental to our understanding of the link with IL-1. At present, the IL-1blockade as therapeutic approach is crucial for many hereditary autoinflammatory diseases, as well as for adult-onset Still's disease, crystal-induced arthropathies, certain skin diseases including neutrophil-triggered skin diseases, Behçet's disease and deficiency of IL-1Ra and other rare fever syndromes. Its role is only marginally important in rheumatoid arthritis and is still under debate with regard to osteoarthritis, type 2 diabetes mellitus, cardiovascular diseases and cancer. This brief historical review focuses on some aspects of IL-1, mainly IL-1β and IL-Ra, in rheumatology. There are many excellent reviews focusing on the IL-1 family in general or with regard to specific diseases or biological discoveries.
28966618 SIRT1/Adenosine Monophosphate-Activated Protein Kinase α Signaling Enhances Macrophage Po 2017 Macrophages are crucially involved in the pathogenesis of rheumatoid arthritis (RA). Macrophages of the M1 phenotype act as pro-inflammatory mediators in synovium, whereas those of the M2 phenotype suppress inflammation and promote tissue repair. SIRT1 is a class 3 histone deacetylase with anti-inflammatory characteristics. However, the role played by SIRT1 in macrophage polarization has not been defined in RA. We investigated whether SIRT1 exerts anti-inflammatory effects by modulating M1/M2 polarization in macrophages from RA patients. In this study, SIRT1 activation promoted the phosphorylation of an adenosine monophosphate-activated protein kinase (AMPK) α/acetyl-CoA carboxylase in macrophages exposed to interleukin (IL)-4, and that this resulted in the expressions of M2 genes, including MDC, FcεRII, MrC1, and IL-10, at high levels. Furthermore, these expressions were inhibited by sirtinol (an inhibitor of SIRT1) and compound C (an inhibitor of AMPK). Moreover, SIRT1 activation downregulated LPS/interferon γ-mediated NF-κB activity by inhibiting p65 acetylation and the expression of M1 genes, such as CCL2, iNOS, IL-12 p35, and IL-12 p40. Macrophages from SIRT1 transgenic (Tg)-mice exhibited enhanced polarization of M2 phenotype macrophages and reduced polarization of M1 phenotype macrophages. In line with these observations, SIRT1-Tg mice showed less histological signs of arthritis, that is, lower TNFα and IL-1β expressions and less severe arthritis in the knee joints, compared to wild-type mice. Taken together, the study shows activation of SIRT1/AMPKα signaling exerts anti-inflammatory activities by regulating M1/M2 polarization, and thereby reduces inflammatory responses in RA. Furthermore, it suggests that SIRT1 signaling be viewed as a therapeutic target in RA.
28488206 The Patient Global Assessment of Disease Activity in Rheumatoid Arthritis: Identification 2017 Jun INTRODUCTION: The patient global assessment of disease activity is a crucial component of various measures of disease activity in rheumatoid arthritis (RA). Our objective was to identify underlying latent traits driving the patient global assessment using a quantitative, multivariable data reduction approach. METHODS: This was a prospective cross-sectional study of consecutive patients with RA. The patient sample was stratified to include 50 patients with patient-provider discordance (i.e., at least 25-mm absolute difference between the patient and provider global assessments) and 20 patients with patient-provider concordance (i.e., less than 25-mm absolute difference between the patient and provider global assessments). Data were collected from the most recent rheumatology visit, including patient characteristics, current RA medications, and comorbidities. Participants completed several validated patient-reported outcome measures. The data were evaluated using factor analysis, and then linear regression was used to determine the variability in the patient global assessment explained by the factor scores. RESULTS: The study included 70 patients with mean age of 61 years, 73% female, and with mean disease duration of 8 years. The means (SD) for the patient and provider global assessments were 44.6 (22.7) and 20.1 (17.7), respectively. Factor analysis yielded eight factors that represented measurements of pain, fatigue, depression or anxiety symptoms, prior diagnosis of depression or anxiety, advanced age and degenerative arthritis, inability to participate, fibromyalgia (clinical diagnosis and Widespread Pain Index), and undetermined. Linear regression analysis showed that fibromyalgia explained the greatest proportion of the variance in the patient global assessment followed by the other factors. CONCLUSION: Latent factors underlying the patient global assessment include pain, depression and anxiety, inability to participate, fibromyalgia, advanced age, and degenerative arthritis.
28571739 Amelioration of adjuvant-induced arthritis in CCDC134-overexpressing transgenic mice. 2017 Aug 19 CCDC134 might be an immune cytokine and plays important and complex roles in the process in vivo. It was proved to illustrate its potent antitumor effects by augmenting CD8(+) T-cell-mediated immunity, but its role in the development of rheumatoid arthritis (RA) remains unclear. In this study, we demonstrated that development of adjuvant-induced arthritis and pro-inflammatory responses were more ameliorated in CCDC134-overexpressing transgenic mice than those in WT mice. The underlying mechanism of CCDC134-induced effects involved inhibition of T helper (Th) 1 and Th17 cell differentiation. These findings indicate that overexpression of CCDC134 exerts potent anti-inflammatory effects through selective modulation of pathogenic Th1 and Th17 cells, and might provide insights into the role of CCDC134 as a unique therapeutic agent for the treatment of rheumatoid arthritis.
29184553 Tumor Necrosis Factor-Alpha Targeting Can Protect against Arthritis with Low Sensitization 2017 Tumor necrosis factor-alpha (TNF-α) blockade is an effective treatment for rheumatoid arthritis (RA) and other inflammatory diseases, but in patients, it is associated with reduced resistance to the infectious agents Mycobacterium tuberculosis and Listeria monocytogenes, among others. Our goal was to model infection and arthritis in mice and to compare etanercept, a currently used anti-TNF-α inhibitor, to an anti-TNF-α vaccine. We developed a murine surrogate of the TNF-α kinoid and produced an anti-murine TNF-α vaccine (TNFKi) composed of keyhole limpet hemocyanin conjugated to TNF-α, which resulted in anti-TNF-α antibody production in mice. We also used etanercept (a soluble receptor of TNF commonly used to treat RA) as a control of TNF neutralization. In a mouse model of collagen-induced arthritis, TNFKi protected against inflammation similar to etanercept. In a mouse model of acute L. monocytogenes infection, all TNFKi-treated mice showed cleared bacterial infection and survived, whereas etanercept-treated mice showed large liver granulomas and quickly died. Moreover, TNFKi mice infected with the virulent H37Rv M. tuberculosis showed resistance to infection, in contrast with etanercept-treated mice or controls. Depending on the TNF-α blockade strategy, treating arthritis with a TNF-α inhibitor could result in a different profile of infection suceptibility. Our TNFKi vaccine allowed for a better remaining host defense than did etanercept.