Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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30535993 | Risk factors for progression and prognosis of rheumatoid arthritis-associated interstitial | 2019 Apr | BACKGROUND: Factors associated with progression and survivals in rheumatoid arthritis-associated interstitial lung disease (RA-ILD) have not been described in a large center China cohort. METHODS: Seven-hundred and ninety-one consecutive RA patients who completed lung HRCT were considered as potential participants in this retrospective cohort study. Determinants of ILD progression were identified through multivariable logistic analysis. Cox hazards analysis was used to determine significant variables associated with survival. RESULTS: Of 307 patients diagnosed with RA-ILD, 266 were finally included. The 3-year survival rate of RA-ILD patients was 81.24%, and the 5-year survival rate was 69.71%. A total of 82 deaths occurred during follow-up, of which 56 died of respiratory failure due to ILD progression and/or pneumonia while 14 with malignancies (8 with lung cancer). Logistic regression analysis showed that anti-CCP antibody high titer positive (OR: 4.03, 95% CI: 1.04-15.69) and DLCO% < 45% (OR: 8.31, 95% CI: 2.17-31.75) were independent risk factors for the ILD progression. Cox hazards analysis revealed that advanced age (> 60 years old) of RA-ILD diagnosis (HR: 2.32, 95% CI: 1.27-4.25) and extensive lung involvement on HRCT (HR: 2.19, 95% CI: 1.24-3.87) were associated with worse survival. Treatment with cyclophosphamide (HR: 0.43, 95% CI: 0.26-0.69) was associated with better survival. CONCLUSIONS: In RA-ILD patients, anti-CCP antibody high titer positive and DLCO% < 45% are risk factors for ILD progression. Advanced age and extensive lung involvement on HRCT, rather than the baseline UIP pattern, independently predict mortality after controlling for potentially influential variables. Furthermore, cyclophosphamide treatment helps to improve the prognosis in real-world experience. | |
32186015 | Classifying rheumatoid arthritis by Traditional Chinese Medicine Zheng: a multi-center cro | 2019 Jun | OBJECTIVE: To assess the relationship between disease symptoms and traditional Chinese medicine (TCM) syndrome (Zheng) in rheumatoid arthritis (RA) patients. METHODS: RA Patients were recruited in Guang'anmen Hospital, China Academy of Chinese Medical Sciences and in the Second Affiliated Hospital of Zhejiang Chinese Medical University, and diagnosed with a particular RA Zheng from their symptoms. Demographic characteristics, self-reported symptoms, and blood samples were collected from patients. All data were input into EpiData and analyzed using SPSS software. RESULTS: The study included 302 RA patients (age range: 18-86 years). All patients were Chinese, and 85.1% were women. Cold and fatigue triggers were reported by 8.6% of patients, followed by triggers such as childbirth (4.3%), cold (3.0%), dampness (2.0%), menopause (1.3%), and psychentonia (0.7%). The most prevalent Zheng was dampness and heat blockage (Shire Yuzu in Chinese, SRYZ), diagnosed in 39.4% of patients (119), followed by phlegm and stagnation blockage (Tanyu Bizu, TYBZ) in 21.5%, liver and kidney deficiency (Ganshen Buzu, GSBZ) in 18.5%, dual deficiency of Qi and blood (Qixue Liangxu, QXLX) in 9.6%, cold and dampness blockage (Hanshi Bizu, HSBZ) in 6%, and wind and dampness blockage (Fengshi Bizu, FSBZ) in 5%. Increased length of time since RA diagnosis was associated with the GSBZ group. Patients diagnosed with the SRYZ Zheng had the highest disease activity score. Patients diagnosed with the QXLX Zheng had the lowest blood platelet counts; patients diagnosed with the QXLX and HSBZ Zhengs had lower C-reactive protein levels and lower health assessment questionnaire scores. Patients diagnosed with the GSBZ and QXLX Zhengs had the highest health assessment questionnaire scores. CONCLUSION: The specific Zheng was related to RA characteristics. The findings suggest that eliminating dampness, cooling the patient, and promoting blood circulation may assist in treating severe RA. | |
31128293 | Delivery of siRNA using folate receptor-targeted pH-sensitive polymeric nanoparticles for | 2019 Aug | Systemic delivery of siRNA to target tissues is difficult to achieve owing to its limited cellular uptake and poor serum stability. Herein, polymeric nanoparticles were developed for systemic administration of siRNA to inflamed tissues. The polymeric nanoparticles were composed of PK3 as a pH-sensitive polymer, folate-polyethyleneglycol-poly(lactide-co-glycolide) as a targeting ligand, and a DOTAP/siRNA core. The polymeric nanoparticles had a mean particle size of 142.6 ± 0.61 nm and a zeta potential of 3.6 ± 0.43 mV. In vitro studies indicated pH-dependent siRNA release from polymeric nanoparticles, with accelerated release at pH 5.0. Cellular uptake was efficient and gene silencing was confirmed by Western blot. In vivo, polymeric nanoparticles were shown to have inflammation-targeting activity and potent therapeutic effects in an adjuvant-induced arthritis rat model. These results suggest that pH-sensitive and folate receptor-targeted nanoparticles are a promising drug carrier for siRNA delivery for rheumatoid arthritis. | |
29747994 | A systematic review of viral exposures as a risk for rheumatoid arthritis. | 2019 Feb | OBJECTIVE: Different viral exposures have been implicated in the etiology of rheumatoid arthritis (RA). Evidence relating to the association between putative viral exposures and the development of RA was reviewed. METHODS: A systematic literature search was conducted using MEDLINE-OVID, EMBASE-OVID, PUBMED and Cochrane library databases. Articles were included if they were case-controls, cross-sectional or cohort studies and were published in English. Case-series were included if there was a lack of other study designs. RESULTS: Of 6724 citations, 48 were included in meta-analysis. Studies had poor quality. PBV19 infection was increased in RA compared to controls [N = 12, odds ratio (OR) 1.77 (95% CI: 1.11; 2.80) p = 0.02 for PVB19 IgG]. IgG anti-EBNA antibodies were not increased in RA (N = 17, p = 0.75), but anti-VCA [N = 18, OR 1.5 (95% CI: 1.07; 2.10), p = 0.02] and anti-EA antibodies [N = 11, OR 2.74 (95% CI: 1.27; 5.94), p = 0.01] were increased in RA. CMV was not associated with RA (N = 13, p = 0.42), nor was HBV (N = 5, p = 0.09). HCV was associated with RA in 7 case-control studies [OR 2.82 (95% CI: 1.35; 5.90), p = 0.006] and one cohort study [hazard ratio (HR) 2.03 (95% CI: 1.27, 3.22), p < 0.01]. Persistent arthritis was increased after Chikungunya fever [N = 2, OR 90 (95% CI: 15.2, 134.3), p = 0.047]. CONCLUSIONS: Studies of RA after viral exposures have poor quality. There is a risk of RA after Parvo B19, HCV and possibly EBV infection. CMV and HBV infections are not associated with RA. CHIKV is associated with the persistent inflammatory arthritis. | |
31242937 | Hand exercise for women with rheumatoid arthritis and decreased hand function: an explorat | 2019 Jun 26 | BACKGROUND: People with hand-related rheumatoid arthritis (RA) experience problems performing activities of daily living (ADL). Compensatory strategies to improve ADL ability have shown effective. Similarly, hand exercise has shown effect on pain, grip strength, and self-reported ability. A combination has shown positive effects based on self-report, but self-report and observation provide distinct information about ADL. The purpose of this study was to examine whether hand exercise as add on to compensatory intervention (CIP) will improve observed ADL ability in RA. METHODS: Women (n = 55) with hand-related RA were randomized to CIP(EXERCISE) (intervention) or CIP only (control). CIP is focused on joint protection, assistive devices, and alternative ways of performing AD. The hand-exercise program addressed range of motion and muscle strength. Primary outcome was change in observed ADL motor ability measured by the Assessment of Motor and Process Skills (AMPS). Baseline measures were repeated after 8 weeks. RESULTS: Improvements in ADL motor ability in CIP(EXERCISE) (mean change = 0.24 logits; 95% CI = 0.09 to 0.39) and CIP(CONTROL) (mean change =0.20 logits; 95% CI = 0.05 to 0.35) were statistically significant, with no differences between groups (mean difference = 0.04 logits; 95% CI = - 0.16 to 0.25). Thirteen (46.4%) participants in the CIP(EXERCISE) and 12 (44.4%) in the CIP(CONTROL) obtained clinically relevant improvements (≥ 0.30 logits) in ADL motor ability; this group difference was not significant (z = 0.15; p = 0.88). CONCLUSION: Adding hand exercise to a compensatory intervention did not yield additional benefits in women with hand-related RA. The study was approved by the ethics committee 14th of April 2014 (H-3-2014-025) and registered at ClinicalTrials.gov 16th of May 2014 (NCT02140866). | |
31834475 | ACPA-positive versus ACPA-negative rheumatoid arthritis: two distinct erosive disease enti | 2020 Apr | The objective of this study is to assess the prevalence, localization, and severity of bone erosions on radiography (RX) and ultrasonography (US) according to ACPA status in patients with rheumatoid arthritis (RA). 78 patients with ACPA-positive (ACPA+) RA and 30 patients with ACPA-negative (ACPA-) RA fulfilling the ACR 1987 and/or ACR/EULAR 2010 criteria were consecutively included. On RX, a modified Sharp erosion score (SHSe) was evaluated by two blinded readers and one adjudicator for discordant cases (number of eroded joints ≤ three). On US, erosions were scored on six bilateral joints (MCP2, 3, 5; MTP2, 3, 5) with a four-point scale to calculate the total US score for erosions (USSe). The mean total SHSe and USSe were 3.7 and 4.4 times higher in the ACPA+ group than in the ACPA- group, respectively (P < 0.001). On both RX and US, the most discriminating joint between the two groups was MTP5, especially in cases with bilateral erosion. Based on multivariate analyses, ACPA + status was associated with erosive RA on RX according to the EULAR 2013 definition criteria [OR 4.4 (95% CI 1.2-16.4)], and on US according to the following two definitions: the presence of at least two eroded joint facets [OR 3.7 (95% CI 1.4-9.9)] or at least one grade 2 joint facet erosion [OR 9.0 (95% CI 2.8-28.4)]. Compared to ACPA- RA, ACPA + RA is associated independently with more severe erosive disease on RX and US. Both US and RX bilateral erosions in MTP5 joints are highly discriminant for ACPA + RA patients (97.8% in US and 100% in RX). | |
30753680 | Expression of STAT3-regulated genes in circulating CD4+ T cells discriminates rheumatoid a | 2019 Jul 1 | OBJECTIVES: Dysregulated signal transduction and activator of transcription-3 (STAT3) signalling in CD4+ T cells has been proposed as an early pathophysiological event in RA. We sought further evidence for this observation, and to determine its clinical relevance. METHODS: Microarray technology was used to measure gene expression in purified peripheral blood CD4+ T cells from treatment-naïve RA patients and disease controls newly recruited from an early arthritis clinic. Analysis focused on 12 previously proposed transcripts, and concurrent STAT3 pathway activation was determined in the same cells by flow cytometry. A pooled analysis of previous and current gene expression findings incorporated detailed clinical parameters and employed multivariate analysis. RESULTS: In an independent cohort of 161 patients, expression of 11 of 12 proposed signature genes differed significantly between RA patients and controls, robustly validating the earlier findings. Differential regulation was most pronounced for the STAT3 target genes PIM1, BCL3 and SOCS3 (>1.3-fold difference; P < 0.005), each of whose expression correlated strongly with paired intracellular phospho-STAT3. In a meta-analysis of 279 patients the same three genes accounted for the majority of the signature's ability to discriminate RA patients, which was found to be independent of age, joint involvement or acute phase response. CONCLUSION: The STAT3-mediated dysregulation of BCL3, SOCS3 and PIM1 in circulating CD4+ T cells is a discriminatory feature of early RA that occurs independently of acute phase response. The mechanistic and functional implications of this observation at a cellular level warrant clarification. | |
31661552 | Neutrophil proteases degrade autoepitopes of NET-associated proteins. | 2020 Jan | Neutrophils can form neutrophil extracellular traps (NETs) to capture microbes and facilitate their clearance. NETs consist of decondensed chromatin decorated with anti-microbial proteins. Here, we describe the effect of neutrophil proteases on the protein content of NETs. We show that the neutrophil serine proteases degrade several neutrophil proteins associated with NETs. Interestingly, the anti-bacterial proteins associated with NETs, such as myeloperoxidase, calgranulin B and neutrophil elastase (NE), seem to be less susceptible to proteolytic degradation than other NET proteins, such as actin and MNDA. NETs have been proposed to play a role in autoimmune reactions. Our data demonstrate that a large number of the autoepitopes of NET proteins that are recognized by autoantibodies produced by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients are also removed by the proteases. In conclusion, neutrophil serine proteases have a major impact on the NET proteome and the proteolytic changes of NET-associated proteins may counteract autoimmune reactions to NET components. | |
31698956 | The role of myeloid-derived suppressor cells in the pathogenesis of rheumatoid arthritis; | 2019 Dec | Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of the immature myeloid cells that are derived from the myeloid progenitors with immunosuppressive functions. MDSCs are accumulated in the inflammatory sites during some autoimmune disorders, such as rheumatoid arthritis (RA) and can be an important factor in the pathogenesis of these diseases. Some research has shown the anti-inflammatory role of MDSCs during the RA progression and supports the hypothesis that MDSCs can be a potential treatment option for autoimmunity with their immunosuppressive activity. In contrast, some papers have reported the opposite effects of MDSCs, and support the hypothesis that MDSCs have a pro-inflammatory role in autoimmune disease. MDSCs functions in RA have not been fully understood, and some controversies, as well as many unanswered questions, remain. Although the two well-known subgroups of MDSCs, M-MDSC, and PMN-MDSC, seem to have different suppressive functions and regulate the immune system responses in a different manner; some studies have shown these cells are converted to each other and even to other cells under different pathological conditions. This review summarises some of the latest papers with respect to the MDSCs functions and discusses the relationship between MDSCs and inflammation in the context of rheumatoid arthritis. | |
31668267 | Serologic Diagnosis of Rheumatoid Arthritis. | 2019 Dec | Accurate diagnosis of inflammatory arthritides remains a challenge because of substantial clinical overlap. To achieve a granular classification for informing clinical decisions, numerous potential serologic biomarkers have been identified. Rheumatologists have settled on rheumatoid factor and anti-citrullinated protein antibodies for the diagnosis of rheumatoid arthritis (RA) based on specificity and sensitivity and their ability to be integrated into clinical algorithms. These biomarkers should be interpreted in their specific clinical context. This article discusses the serologic basis for the diagnosis of RA, how these biomarkers have framed conceptualization of the pathogenesis of RA, and the inherent limitations in their use. | |
31273459 | [Reality of care for musculoskeletal diseases at the population level : Results of the PRO | 2019 Oct | BACKGROUND: The objective of the research consortium PROCLAIR was to gain population level knowledge on the treatment of patients with rheumatoid arthritis (RA), axial spondylarthritis (axSpA) and osteoarthritis (OA) in Germany. AIMS: A main question of the consortium was whether it is possible to identify groups of people who were exposed to a particular risk of undersupply or oversupply of treatment. In addition, the study investigated the validity of claims data for these diseases as a basis for further studies. PATIENTS AND METHODS: Cross-sectional surveys were carried out among insurees of the BARMER statutory health insurance fund whose claims data included RA, axSpA and OA diagnoses. The questionnaire data were linked with the claims data of the insured persons if they agreed. RESULTS: In all three diseases risk groups for care deficits could be identified. Persons with RA who are not treated by a specialist have less access to drug treatment. Physical therapy is prescribed for all three diagnoses at a low level, even for people undergoing joint replacement surgery. A connection between depressive symptoms and disease activity or function in axSpA was shown. In addition to the results relevant to care, the PROCLAIR network has also made contributions to critically assess the quality of health insurance data. DISCUSSION: The combination of billing data with survey data enables a comprehensive description of the treatment of musculoskeletal diseases. Particularly relevant factors are the specialization of the physician, sociodemographic parameters of the patients and the region of residence. In particular, access to treatment cannot be investigated in randomized clinical trials. | |
31338568 | The impact of gender on time to rheumatoid arthritis classification: a retrospective analy | 2019 Dec | The objective is to compare the time to fulfillment of 1987 and 2010 ACR/EULAR classification criteria between female and male patients with rheumatoid arthritis (RA) and to assess the potential impact of gender on the time to DMARD therapy. Time from first provider-documented joint swelling to fulfillment of 1987 and 2010 ACR/EULAR criteria was measured in a population-based cohort of adults with incident RA, who were stratified by male or female gender. Disease characteristics, time to start of DMARD therapy, and choice of initial DMARD were compared between groups. The study included 214 patients with RA (148 females and 66 males). Median times from first joint swelling to fulfillment of 1987 (6.5 vs 2.5 days, p = 0.48) and 2010 (1 vs 0 days, p = 0.34) classification criteria were not different between female and male patients overall. There was no difference in time to first DMARD therapy in female vs male patients (15.5 vs 16 days, p = 0.90), and methotrexate was used most frequently as first DMARD in both genders (61% female vs 64% male, p = 0.76). Among the 49 female and 20 male RF/ACPA-negative patients, females experienced a higher median time from first joint swelling to fulfillment of the 1987 (65 vs 11 days, p = 0.063) and 2010 (65 vs 0 days, p = 0.035) classification criteria. Overall, there was no significant delay in meeting 1987 and 2010 ACR/EULAR classification criteria between female and male RA patients, though time to meeting both 1987 and 2010 criteria was slightly longer in males compared with females. Among seronegative patients, females experienced a significant delay to meeting 2010 criteria from first clinically detected synovitis. | |
30957538 | [The importance of microRNAs in the development of systemic autoimmune disorders]. | 2019 Apr | MicroRNAs (miRNAs) are 18-25 nucleotide long, single stranded, endogenous, non-coding small RNAs playing an important role in regulating gene expression at posttranscriptional level. miRNAs control approximately 90% of protein-coding genes, and play a central role in various biological processes including immune cell lineage commitment, differentiation, proliferation, apoptosis and maintenance of immune homeostasis. Changes in the expression of certain miRNAs may lead to the development of many diseases, including systemic autoimmune diseases. In this study, we summarize the biogenesis of miRNAs, their role in regulation of the immune system, and review the latest research findings in systemic lupus erythematosus, primary Sjögren's syndrome, rheumatoid arthritis and systemic sclerosis. In the future, miRNAs may help not only in establishing diagnosis and prognosis but potentially serve as targets for modern therapeutic approaches in autoimmune diseases. Orv Hetil. 2019; 160(15): 563-572. | |
31706348 | Burden of rheumatoid arthritis on patients' work productivity and quality of life. | 2019 Nov 9 | BACKGROUND: To determine the burden of Rheumatoid Arthritis (RA) on patients' work productivity and health related quality of life (HRQoL), and examine the influence of several exposure variables; to analyze the progression of RA over 1 year and its impact on work productivity and HRQoL. METHODS: International multicenter prospective survey including patients in 18 centers in Argentina, Brazil, Colombia and Mexico with diagnosis of RA and aged between 21-55 years. The following standard questionnaires were completed at baseline and throughout a 1-year follow-up: WPAI:RA, WALS, WLQ-25, EQ-5D-3 L and SF-36. Clinical and demographic variables were also collected through interview. RESULTS: The study enrolled 290 patients on baseline visit. Overall mean scores at baseline visit were: WPAI:RA (presenteeism) = 29.5% (SD = 28.8%); WPAI:RA (absenteeism) = 9.0% (SD = 23.2%); WPAI:RA (absenteeism and presenteeism) = 8.6% (SD = 22.6%); WALS = 9.0 (SD = 6.1); WLQ-25 = 7.0% (SD = 5.1%); SF-36 Physical Scale = 39.1 (SD = 10.3) and Mental Scale = 45.4 (SD = 11.3); EQ-5D-3 L VAS = 69.8 (SD = 20.4) and EQ-5D-3 L index = 0.67 (SD = 0.23). Higher educational levels were associated with better results in WLQ-25, while previous orthopedic surgeries reduced absenteeism results of WPAI:RA and work limitations in WLQ-25. Higher disease duration was associated with decreased HRQoL. Intensification of disease activity was associated with decreased work productivity and HRQoL, except in WLQ-25. In the longitudinal analysis, worsening in disease activity was associated with a decrease in both work productivity and HRQoL. CONCLUSIONS: RA patients are dealing with workplace disabilities and limitations and loss in HRQoL, and multiple factors seems to be associated with this. Worsening of disease activity further decreased work productivity and HRQoL, stressing the importance of disease tight control. | |
31642025 | Upadacitinib: First Approval. | 2019 Nov | Upadacitinib (Rinvoqâ„¢), an orally-administered Janus kinase 1 (JAK-1) inhibitor, is being developed by AbbVie for the treatment of rheumatoid arthritis. In August 2019, based on positive results from multinational phase III trials conducted in patients with rheumatoid arthritis, upadacitinib received marketing approval in the USA for the treatment of moderately to severely active rheumatoid arthritis and an inadequate response or intolerance to methotrexate. This article summarizes the milestones in the development of upadacitinib leading to this first approval for the treatment of rheumatoid arthritis. | |
31819160 | Proteomic analysis to define predictors of treatment response to adalimumab or methotrexat | 2020 Jun | Seropositivity for anti-citrullinated peptide antibodies (ACPA) in patients with rheumatoid arthritis (RA), a chronic autoimmune arthritis, is associated with worse long-term disease outcomes. ACPA is ubiquitously tested in RA patients, but other autoantibodies exist (in both citrullinated and non-citrullinated form) which may provide additional information on RA subtypes and/or treatment response. We used a multiplex bead-based assay of 376 autoantibodies to test associations between these autoantibodies and treatment response in RA patients. Clusters of patients with similar autoantibody expression were defined and cluster membership was associated with treatment response. Thirty-four autoantibodies were differentially expressed in RA patients compared with healthy controls; citrullinated vimentin was associated with treatment response. A selection of citrullinated autoantibodies was found to be associated with treatment response in a subanalysis of ACPA-negative RA patients. Finer ACPA specificities in ACPA-negative RA patients may be predictive of treatment response and could represent a rich vein of future study. | |
31828544 | The knowledge level of rheumatoid arthritis patients about their disease in a developing c | 2020 Apr | OBJECTIVES: To assess disease-related knowledge of rheumatoid arthritis (RA) patients PATIENTS AND METHODS: Consecutive RA patients were invited from the rheumatology departments of BSMM University, Dhaka, Bangladesh. The Bangla version of the Patient Knowledge Questionnaire (B-PKQ) was used. Correlations between the B-PKQ scores and clinical-demographic data were measured using Pearson's correlation coefficient. Impact of independent variables on the level of knowledge about RA was analyzed through multiple regression analysis. Possible explanatory variables included the following: age, disease duration, formal education level, and Bangla Health Assessment Questionnaire (B-HAQ) score. Analysis of variance (ANOVA) was used to test the difference between demographical, clinical, and socioeconomic variables. For statistical analysis, SPSS statistics version 20 was used. RESULTS: A total of 168 RA patients could be included. The mean B-PKQ score was 9.84 (range 1-20) from a possible maximum of 30. The mean time for answering the questionnaire was 24.3 min (range 15-34). Low scores were observed in all domains but the lowest were in medications and joint protection/energy conservation. Knowledge level was higher (15.5) in 6 patients who had RA education before enrollment. B-PKQ showed positive correlation with education level (r = 0.338) and negative correlation with HAQ (r = -0.169). The B-PKQ showed no correlation with age, disease duration, having first degree family member with RA, education from other sources (neighbor, RA patient, nurses), or information from mass media. CONCLUSIONS: Disease-related knowledge of Bangladeshi RA patients was poor in all domains. Using these findings, improved education and knowledge will result in better disease control.Key Points• Little is known about the knowledge of RA patients regarding their disease and its treatment in Bangladesh and in developing countries in general.• We found that the knowledge of Bangladeshi RA patients regarding their disease was poor in all domains; it correlated positive with education level and negative with function (HAQ), but showed no correlation with age or disease duration.• The findings of this study can be used for improving current patient education programs by health professionals and through mass media.• Better disease control of RA may be achieved by improving patient knowledge in a developing country like Bangladesh, but also in other parts of the world. | |
31736958 | Long Non-coding RNAs Genes Polymorphisms and Their Expression Levels in Patients With Rheu | 2019 | Long non-coding RNAs (lncRNAs) are increasingly recognized to play important roles in multiple autoimmune diseases. This study aimed to evaluate the association of four lncRNAs (ANRIL, lnc-DC, MALAT1, ZFAS1) genes single nucleotide polymorphisms (SNPs) with susceptibility to rheumatoid arthritis (RA) patients, as well as their expression levels. Seventeen SNPs of the four lncRNAs were genotyped in a cohort of 660 RA patients and 710 controls using improved multiple ligase detection reaction (iMLDR). The lncRNAs expressions in peripheral blood mononuclear cells (PBMCs) from 120 RA patients and 120 controls were detected by qRT-PCR. No significant differences were found for the allele and genotype frequencies distribution of ANRIL SNPs (rs1412830, rs944796, rs61271866, rs2518723, rs3217992), lnc-DC SNPs (rs7217280, rs10515177), MALAT1 SNPs (rs619586, rs4102217, rs591291, rs11227209, rs35138901), ZFAS1 SNPs (rs237742, rs73116127, rs6125607, rs6125608) between RA patients and normal controls (all P > 0.05). The genotype effects of dominant and recessive models were also evaluated, but no significant association was found. In addition, our results demonstrated that the rs944796 G allele, rs2518723 T allele, rs3217992 T allele frequencies were significantly associated with anti-CCP in RA patients (all P < 0.05). The haplotype CGTA frequency for ZFAS1 was significantly higher in RA patients (P = 0.036). Compared with normal controls, the expression levels of ANRIL, lnc-DC, MALAT1, ZFAS1 in PBMCs were significantly reduced in RA patients (all P < 0.001). Moreover, ZFAS1 expression was negatively associated with CRP in RA patients (P = 0.002). In summary, ANRIL, lnc-DC, MALAT1, and ZFAS1 genes SNPs were not associated with RA susceptibility, while altered ANRIL, lnc-DC, MALAT1, ZFAS1 levels in RA patients suggested that these lncRNAs might play a role in RA. | |
31099177 | Evaluation of risk factors for atherosclerosis using carotid ultrasonography in Japanese p | 2019 Jul | AIM: Previous studies have reported that patients with rheumatoid arthritis (RA) have a higher risk of developing cardiovascular disease (CVD) than the general population. A major cause of CVD is atherosclerosis, which can be evaluated with carotid ultrasonography (US). As far as we know, there have been no large-scale carotid artery US studies in Japanese patients with RA. The aim of this study was to identify the risk factors for atherosclerosis in Japanese patients with RA. METHODS: The study subjects underwent physical examinations, laboratory tests and US examination, and answered a questionnaire about their lifestyle. Carotid US was performed to measure the maximum carotid intima media thickness (max cIMT) and to detect plaques. RESULTS: Atherosclerosis was detected in 238 patients (52%). Age, hypertension, and total/high-density lipoprotein cholesterol ratio were positively related to max cIMT. Presence of plaques was related to age, Disease Activity Score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR), smoking, and any biological treatment. DAS28-ESR correlated positively not with cIMT but with the development of plaques in our patients with low disease activity (average DAS28-ESR of 2.7). CONCLUSION: Disease Activity Score of 28 joints-erythrocyte sedimentation rate was related to the size and number of plaques, whereas only traditional risk factors were related to max cIMT. This indicated that the inflammatory conditions of RA could affect the formation of atherosclerotic plaques. For the management of CVD in patients with RA, it may be important to control not only traditional risk factors, but also RA disease activity. | |
30998570 | Physician's Experience and Disease Activity Affect the Impact of Ultrasound on the Treatme | 2019 Aug | BACKGROUND/OBJECTIVE: The aim of this cross-sectional study was to explore which factors affect the impact of musculoskeletal ultrasound (MUS) on the treatment proposal among rheumatologists with different degree of experience. METHODS: Sixteen clinical vignettes summarized data from rheumatoid arthritis (RA) outpatients; vignettes included clinical evaluation and a blank section for a first treatment proposal; MUS information was then added, based on German Ultrasound score, followed by a blank section for treatment re-consideration, if applicable. During a 6 months period, each vignette was concomitantly presented to six trainees and six senior rheumatologists (SR); three SR had ≥15 years of experience. Participants were blinded to colleagues' responses. Appropriated statistics were used. RESULTS: Vignettes included data from female patients, who had a mean ± SD age of 43.3 ± 9 years, 7.6 ± 3.5 years of disease duration and comorbidities (68.8%). MUS induced treatment modification in 24% of evaluations, with similar percentage among SR and trainees. Within SR, more experienced rheumatologists (≥15 years) never translated MUS findings in a different treatment proposal, compared to 34% of those with lesser experience, p ≤ 0.0001. There were 60 clinical scenarios each, with remission and moderate disease activity, and 36 clinical scenarios each, with low and high disease activity. MUS-induced treatment modifications were more frequent in scenarios with low and moderate disease activity, compared to remission and high disease activity, p = 0.008. CONCLUSIONS: Physician's experience and disease activity level affect the impact of MUS on the treatment decision in RA outpatients. RA patients with intermediate disease activity may benefit from MUS incorporation to standard assessments. |