The Assessment of Muscle Mass and Function in Patients with Long-Standing Rheumatoid Arthritis.
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ABSTRACT:
SUBMITTER: Yun HW
PROVIDER: S-EPMC8397223 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:At a given time, rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms is still poorly understood. Because previous microarrays studies have only focused on late RA stages, we aimed to compare the biological and molecular profiles in early and long-standing (LS) RA. Synovial biopsies obtained by arthroscopy were performed in 4 early untreated RA patients, 4 LS treated RA patients and 7 control patients. Extracted mRNA were linearly amplified and used for large-scale gene expression profiling by cDNA arrays. By gene ontology analysis, the different gene combinations obtained by comparison of early, LS RA and normal synovium were used to identify the biological processes, molecular functions and pathways involved at each stage. Three combinations of 719, 116 and 52 transcripts dissociated respectively early from LS RA patients, early or LS RA from normal synovium. We identified several gene clusters and distinct molecular signatures specifically related to early or LS RA suggesting the involvement of different pathological mechanisms at each stage. Early and LS RA have distinct molecular signatures with the participation of different biological processes during the course of the disease. These results suggest that a better knowledge of the main biological processes involved at a given RA stage might help the rheumatologist to choose the more appropriate treatment.
2008-10-03 | GSE13026 | GEO
Project description:At a given time, rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms is still poorly understood. Because previous microarrays studies have only focused on late RA stages, we aimed to compare the biological and molecular profiles in early and long-standing (LS) RA. Synovial biopsies obtained by arthroscopy were performed in 4 early untreated RA patients, 4 LS treated RA patients and 7 control patients. Extracted mRNA were linearly amplified and used for large-scale gene expression profiling by cDNA arrays. By gene ontology analysis, the different gene combinations obtained by comparison of early, LS RA and normal synovium were used to identify the biological processes, molecular functions and pathways involved at each stage. Three combinations of 719, 116 and 52 transcripts dissociated respectively early from LS RA patients, early or LS RA from normal synovium. We identified several gene clusters and distinct molecular signatures specifically related to early or LS RA suggesting the involvement of different pathological mechanisms at each stage. Early and LS RA have distinct molecular signatures with the participation of different biological processes during the course of the disease. These results suggest that a better knowledge of the main biological processes involved at a given RA stage might help the rheumatologist to choose the more appropriate treatment. PBMC then RNA were extracted from synovial biopsies of 4 eraly RA patients, 4 long-standing RA patients and from 7 normal synovium used as control. Each sample was hybridized three times in different nylon membrane.
2010-06-25 | E-GEOD-13026 | biostudies-arrayexpress
Project description:BackgroundMuscle mass loss is common in long-standing rheumatoid arthritis (RA). The aim was to explore the prevalence and effects of RA disease characteristics in patients with early RA.MethodsThis cross-sectional study was carried out based on a Chinese RA cohort and control subjects. The body composition (BC) was assessed using bioelectric impedance analysis. Myopenia was defined by an appendicular skeletal muscle mass index of ≤ 7.0 kg/m2 in men and ≤ 5.7 kg/m2 in women. Physical dysfunction was defined as a health assessment questionnaire disability index > 1. Propensity score matching was performed to balance age and gender differences among patients with early RA (disease duration ≤ 12 months) and established RA, and controls (with 1:3:3 matching).ResultsIn total, 2017 controls and 1,008 patients with RA were recruited for this study. Among the patients with RA, there were 190 (18.8%) patients with early RA, with a median disease duration of 7 (4, 11) months. The matched patients with early RA (n = 160) showed a higher prevalence of myopenia than the matched controls (41.3 vs. 15.8%, P < 0.0167), but no difference was found in the matched patients with established RA (41.3 vs. 50.4%, P > 0.0167). Compared with the patients with established RA, the patients with early RA exhibited higher disease activity scores [disease activity score in 28 joints with four variables including C-reactive protein (DAS28-CRP): median 4.76 vs. 3.93, P < 0.001] and a higher prevalence of physical dysfunction (26.3 vs. 19.4%, P = 0.035). In the patients with early RA, patients with myopenia showed a higher prevalence of physical dysfunction than those without myopenia (41.3 vs. 15.5%, P < 0.001), among which walking and common daily activities were the most involved subdimensions. Multivariate logistic regression analysis showed that DAS28-CRP was positively associated with myopenia [adjusted odds ratio (AOR) 1.558, 95% CI (1.138-2.132)], and myopenia [AOR 2.983, 95% CI (1.192-7.465)] was independently associated with physical dysfunction in the patients with early RA.ConclusionOur data indicate the importance of early detection of muscle involvement in the early stage of RA and imply the significance of early aggressive control of disease activity for the prevention of myopenia and physical dysfunction in patients with early RA. Our study provides a new perspective on RA management.
| S-EPMC9727302 | biostudies-literature
Project description:To evaluate corneal densitometry and anterior segment parameters of rheumatoid arthritis (RA) patients and compare these results with those of age-matched healthy control subjects.Anterior segment parameters and corneal densitometry of patients with RA and healthy control subjects were assessed by Scheimpflug corneal topography. For densitometry analysis, the 12-mm diameter area of the cornea was subdivided into four concentric radial zones and anterior, central, and posterior layers based on corneal depth. Right eyes of subjects were used for statistical analysis.Twenty-three consecutive patients with RA and 22 healthy control subjects were included in the study. There was no significant difference with regard to age (p=0.487) or gender (p=0.514). When anterior segment parameters of both groups were compared, no significant difference was found (p>0.05). Total corneal densitometry values were statistically higher in the RA group (p=0.030). In addition, when subdivisions of the cornea were evaluated, higher densitometry values were found in the RA group in 0-2 and 2-6 mm radial zones both in the anterior and total depth (p=0.001, p=0.003 for the 0-2 mm zone and p=0.002, p=0.009 for the 2-6 mm zone). Corneal densitometry measurement was not correlated with central corneal thickness or simulated keratometry value in RA patients or healthy control subjects.The corneal densitometry values were higher in RA patients when compared to healthy control subjects, even if they had clinically clear corneas. Corneal densitometry as an objective measure of corneal clarity warrants further studies in order to ascertain its clinical relevance in RA patients.
| S-EPMC5468523 | biostudies-other
Project description:To correlate the level of fibrocytes in peripheral blood, synovial tissue and in vitro culture in rheumatoid arthritis (RA) with changes in disease activity, imaging and pulmonary function. Twenty patients with early RA (ERA) and 20 patients with long-standing RA (LRA) were enrolled in a 6-month prospective study. Sixteen patients undergoing wrist arthroscopy were healthy controls. Patients with RA underwent pulmonary function tests, ultrasound and synovial ultrasound-guided needle biopsy of the same wrist at baseline and 6 months. Wrist MRI was performed at baseline (all) and 6 months (ERA). Circulating fibrocytes were measured by flow cytometry, in vitro by the number of monocytes that were differentiated to fibrocytes and in synovial biopsies by counting in histological sections. Fibrocytes were primarily located around vessels and in the subintimal area in the synovium. Fibrocyte levels did not decline during the trial despite effective RA treatment. In the ERA group, increased synovitis assessed by ultrasound was moderate and strongly correlated with an increase in circulating and synovial fibrocyte levels, respectively. Increased synovitis assessed by MRI during the trial in the ERA group was moderately correlated with both increased numbers of circulating and cultured fibrocytes. Absolute diffusion capacity level was overall weakly negatively correlated with the level of circulating and synovial fibrocytes. The decline in diffusion capacity during the trial was moderately correlated with increased levels of synovial fibrocytes. Our findings suggest that fibrocytes are involved in RA pathogenesis, both in the synovium and the reduction in lung function seen in a part of patients with RA. NCT02652299.
| S-EPMC7938972 | biostudies-literature
Project description:BackgroundNo previous studies have characterized a patient's experience of rheumatoid arthritis (RA) management in Greece and unmet needs may exist despite a broad range of available treatments. Therefore, we assessed quality of life (QoL), functional ability, and healthcare resource utilization in patients with established RA and receiving treatment in a tertiary care setting in Greece.MethodsThis was a prospective, observational cohort of patients aged ≥18 years, receiving any type of treatment for RA, and followed for 12 months at 7 rheumatology referral centers across mainland Greece (NCT01001182). Patient data were collected at the initial visit and 3, 6, and 9 months. QoL was evaluated using the Euro Quality of Life-5 dimensions questionnaire (EQ-5D) and functional ability was evaluated using the Health Assessment Questionnaire (HAQ).ResultsA total of 210 patients with RA were enrolled (76.7% women, mean ± standard deviation [SD] age: 59.1 ± 12.6 years, median [interquartile range] disease duration: 11.9 [5.0-16.0] years). Baseline mean ± SD EQ-5D and HAQ scores were 0.57 ± 0.32 and 0.75 ± 0.63, respectively, and remained largely unchanged throughout the study. Post-hoc comparison showed that patients receiving non-biologic disease-modifying antirheumatic drugs (non-bDMARDs) had significantly higher EQ-5D and lower HAQ-DI scores compared with those receiving biologic DMARDs. A majority of patients reported having difficulty doing housework or other duties (61.4 and 61.9%, respectively), and 55.2% reported needing external support for these tasks. Positive correlation was observed between QoL and functional ability. Hospitalization at least once during the study occurred in 9.5% of the patients, and 12.5% of these cases were due to exacerbation of RA. At baseline, 52.4% of the patients were retired, with 38.5% of retirees having retired early due to RA. Among the patients who were retired at baseline, the mean ± SD period from actual retirement to expected retirement age was 12.1 ± 8.1 years.ConclusionQoL and functional ability were positively correlated in patients with long-standing RA, with a large proportion showing impairments in both. Timely, target-oriented treatment initiated as soon as possible after diagnosis may help to improve patient-reported outcomes and limit the burden of RA.Trial registrationClinicalTrials.gov NCT01001182 . Registered 23 October 2009.
| S-EPMC6489275 | biostudies-literature
Project description:IntroductionRheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia.MethodsSynovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation.ResultsThree combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA.ConclusionsEarly and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment.
| S-EPMC2714155 | biostudies-literature
Project description:Long noncoding RNAs (lncRNAs) belong to a new class of noncoding RNAs. Emerging evidence has shown that lncRNAs play a crucial role in the regulation of autoimmunity. During the past few years, the modifying effects of lncRNAs in rheumatoid arthritis (RA) have drawn much attention. However, the underlying molecular mechanisms involved in RA pathogenesis remain largely unknown. Herein, we aim to investigate the expression profile of lncRNAs in patients with RA and identify promising targets for RA diagnosis and treatment.Microarray screening and real-time PCR of lncRNAs were performed in the serum from 3 RA patients and 3 healthy controls. Significantly differentially expressed lncRNAs were selectively verified in 43 RA patients and 40 healthy controls by real-time PCR. LncRNA-mRNA co-expression and gene-pathway networks were assured in the bioinformatics analysis.After microarray analysis, there were a total of 73 up-regulated and 61 down-regulated lncRNAs as well as 128 up-regulated and 37 down-regulated mRNAs in the serum of RA patients. After validated by real-time PCR, 5 of these lncRNAs were found to be significantly up-regulated in the serum of RA patients including RNA143598, RNA143596, HIX0032090, IGHCgamma1, and XLOC_002730. Significant association was observed between these lncRNAs and the disease course, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) as well as anti-cyclic citrullinated peptide (anti-CCP) antibody. Computational analysis revealed that 55 of the differentially expressed mRNAs were associated with 41 lncRNAs involved in signaling pathways of toll like receptors (TLRs), nuclear factor-kappa B (NF-κB), and cytokine, especially the IRF3/IRF7 mediated signaling transduction.
2019-12-31 | GSE94519 | GEO
Project description:Advances in microbiome research suggest involvement in chronic inflammatory diseases such as rheumatoid arthritis (RA). Searching for initial trigger(s) in RA, we compared transcriptome profiles of highly inflamed RA synovial tissue (RA-ST) and osteoarthritis (OA)-ST with 182 selected reference transcriptomes of defined cell types and their activation by exogenous (microbial) and endogenous inflammatory stimuli. Screening for dominant changes in RA-ST demonstrated activation of monocytes/macrophages with gene-patterns induced by bacterial and fungal triggers. Gene-patterns of activated B- or T-cells in RA-ST reflected a response to activated monocytes/macrophages rather than inducing their activation. In contrast, OA-ST was dominated by gene-patterns of non-activated macrophages and fibroblasts. The difference between RA and OA was more prominent in transcripts of secreted proteins and was confirmed by protein quantification in synovial fluid (SF) and serum. In total, 24 proteins of activated cells were confirmed in RA-SF compared to OA-SF and some like CXCL13, CCL18, S100A8/A9, sCD14, LBP reflected this increase even in RA serum. Consequently, pathogen-like response patterns in RA suggest that direct microbial influences exist. This challenges the current concept of autoimmunity and immunosuppressive treatment and advocates new diagnostic and therapeutic strategies that consider microbial persistence as important trigger(s) in the etiopathogenesis of RA.
| S-EPMC7220941 | biostudies-literature
Project description:ObjectivesTofacitinib is an oral Janus kinase inhibitor for the treatment of RA. We evaluated radiographic progression in tofacitinib-treated patients with RA for up to 3 years in two pooled long-term extension (LTE) studies (ORAL Sequel; A3921041) (primary analysis), and for up to 5 years using data integrated from one phase (P)2 (A3921068), two P3 (ORAL Start; ORAL Scan) and two LTE studies (exploratory analysis).MethodsIn LTE studies, patients received tofacitinib 5 mg twice daily (BID) or 10 mg BID as monotherapy or with conventional synthetic (cs)DMARDs. Radiographic outcomes up to 3 years: least squares mean (LSM) change from baseline in van der Heijde modified Total Sharp Score (ΔmTSS), erosion score (ΔES) and joint space narrowing (ΔJSN) score; proportion of patients with no radiographic progression (ΔmTSS ≤0.5); proportion of patients with no new erosions (ΔES ≤0.5). ΔmTSS was evaluated for up to 5 years in an exploratory analysis.ResultsFor all tofacitinib-treated patients with radiographic data available at LTE month 36 (n = 414), LSM ΔmTSS was 1.14, LSM ΔES was 0.66, LSM ΔJSN was 0.74, and 74.3% and 86.2% of patients showed no radiographic progression and no new erosions, respectively. Similar values were observed regardless of tofacitinib dose, or whether patients received tofacitinib as monotherapy or with csDMARDs. In an exploratory analysis of integrated P2/P3/LTE studies, LSM ΔmTSS was 3.34 at month 60 (n = 269).ConclusionLimited progression of structural damage was observed in tofacitinib-treated patients up to 5 years, with similar results for tofacitinib used as monotherapy or combination therapy up to 3 years.Trial registrationClinicalTrials.gov (http://clinicaltrials.gov): NCT01164579; NCT01039688; NCT00847613; NCT00413699; NCT00661661.
| S-EPMC8023998 | biostudies-literature