Function In Rheumatoid Arthritis Research Articles

Methotrexate, blood pressure and arterial function in rheumatoid arthritis: study protocol.

This article discusses the rationale and design of the study "Methotrexate, blood pressure, and arterial function in rheumatoid arthritis". The recognition that immune activation and excess inflammation favor atherosclerosis has stimulated a significant body of research not only to identify new drugs targeting these pathways but also to repurpose (reposition) existing immunomodulatory medications as atheroprotective agents. Observational studies in patients with rheumatoid arthritis have reported that treatment with methotrexate, a traditional disease-modifying antirheumatic drug, is associated with a significantly lower risk of cardiovascular morbidity and mortality when compared with other disease-modifying antirheumatic drugs. One potential mechanism accounting for the reduced cardiovascular risk associated with methotrexate is the lowering effect on arterial blood pressure. However, such effect has only been observed in cross-sectional and observational studies. Given the established role of hypertension as a leading cardiovascular risk factor, these observations justify an intervention comparison study, the focus of this article, investigating the temporal effects of methotrexate on blood pressure and various surrogate markers of atherosclerosis in patients with rheumatoid arthritis. The results of this study might lead to the repurposing of methotrexate for cardiovascular prevention in patients with and without autoimmune disorders.Clinical Trial Registration: NCT03254589 (ClinicalTrials.gov).

Biologic and targeted synthetic disease-modifying anti-rheumatic drugs improve body composition in rheumatoid arthritis patients more than conventional synthetic disease-modifying anti-rheumatic drugs: Results from the PRESENT study.

The effects of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on body composition and muscle function in rheumatoid arthritis (RA) patients requiring treatment enhancement were compared. This multicenter, prospective, observational study (PRESENT Study) divided RA patients non-randomly into a csDMARD group (n = 100) and a b/tsDMARD group (n = 100). Changes in body composition and muscle function were examined in 80 patients in each group followed for 52 weeks. The percentages of new-onset and improved sarcopenia over 1 year were investigated. Patients in the b/tsDMARD group were divided into three groups by drug type: TNF inhibitors (n = 30), non-TNF inhibitors (n = 23), and JAK inhibitors (n = 27). Baseline median age and disease duration were 70.0 and 4.0 years, respectively. Changes in weight (24 and 52 weeks) and muscle mass (52 weeks) were significantly higher in the b/tsDMARD group (p = .035, p < .001, and p = .002, respectively). On multivariate logistic regression analysis, b/tsDMARD treatment (OR 3.21, p = .002), DAS28-ESR (OR 0.65 p = .011), and muscle mass (OR 0.90, p = .023) were independently associated with increased muscle mass at 52 weeks. The percentages of new-onset and improved sarcopenia were almost equal. There were no significant differences in the time-dependent changes (52 weeks) of clinical status, body composition, muscle function, and status of sarcopenia among TNF inhibitors, non-TNF inhibitors, and JAK inhibitors. Weight and muscle mass increased significantly more with b/tsDMARD than with csDMARD treatment. There were no differences in body composition changes by mode of action with b/tsDMARDs.

Epicardial Adipose Tissue and Left Ventricular Systolic Function in Rheumatoid Arthritis Assessed by Two-Dimensional Speckle Tracking Echocardiography.

Introduction Epicardial adipose tissue (EAT) is an emerging cardiovascular biomarker. Subclinical left ventricular (LV) systolic dysfunction is common in rheumatoid arthritis (RA). The aim of this study was to assess LV systolic function using two-dimensional speckle tracking echocardiography (2D-STE) and investigate its association with EAT in RA patients without clinical cardiovascular disease (CVD). Methods 60 RA patients without manifestations of CVD and 60 age- and gender-matched healthy controls have been recruited for the study. We assessed LV systolic function and EAT in all subjects using conventional echocardiography and 2D-STE. EAT was measured as the relative echo-free region between the free wall of the right ventricle and the visceral layer of the pericardium at end-systole. Results Global longitudinal strain (GLS) was decreased and EAT was increased in the RA group compared to the control group. GLS was reduced as EAT increased in RA patients (r=-0.273, P=0.035). After adjusting for confounders, multivariate linear regression analysis revealed a weakened correlation between EAT and GLS.Age and disease activity scores28 were independent factors influencing GLS in RA. Conclusion RA patients have significantly thickened EAT compared with controls. 2D-STE can detect early LV myocardial systolic dysfunction in RA, as shown by lower GLS.Accumulation of EAT is associated with lower GLS, but older age and higher disease activity may play a greater role in LV myocardial systolic dysfunction in RA.

Assessment of Disease Activity, Structural Damage, and Function in Rheumatoid Arthritis.

The primary goal in the treatment of rheumatoid arthritis (RA) is to control disease activity, prevent structural damage in joints, and normalize function. Therefore, reliable tools are needed to disease activity, physical function, and radiographic progression in RA. We herein describe methods recently used to assess RA.

Asperosaponin VI facilitates the regeneration of skeletal muscle injury by suppressing GSK‐3β‐mediated cell apoptosis

AbstractAsperosaponin VI (ASA VI) is a bioactive triterpenoid saponin extracted from Diptychus roots, of Diptyl, and has previously shown protective functions in rheumatoid arthritis and sepsis. This study investigates the effects and molecular mechanisms of ASA VI on skeletal muscle regeneration in a cardiotoxin (CTX)‐induced skeletal muscle injury mouse model. Mice were subjected to CTX‐induced injury in the tibialis anterior and C2C12 myotubes were treated with CTX. Muscle fiber histology was analyzed at 7 and 14 days postinjury. Apoptosis and autophagy‐related protein expression were evaluated t s by Western blot, and muscle regeneration markers were quantified by quantitative polymerase chain reaction. Docking studies, cell viability assessments, and glycogen synthase kinase‐3β (GSK‐3β) activation analyses were performed to elucidate the mechanism. ASA VI was observed to improve muscle interstitial fibrosis, remodeling, and performance in CTX‐treated mice, thereby increased skeletal muscle size, weight, and locomotion. Furthermore, ASA VI modulated the expression of apoptosis and autophagy‐related proteins through GSK‐3β inhibition and activated the transcription of regeneration genes. Our results suggest that ASA VI mitigates skeletal muscle injury by modulating apoptosis and autophagy via GSK‐3β signaling and promotes regeneration, thus presenting a probable therapeutic agent for skeletal muscle injury.

Assessment of physical functioning in rheumatoid arthritis patients after rituximab therapy using health assessment questionnaire-disability index

The most frequently used instrument for measuring self-reported physical function in rheumatoid arthritis is the health assessment questionnaire – disability index. The objective of this study was to assess the effects of treatment with rituximab on patient-reported outcomes in severe rheumatoid arthritis patients. Rituximab was initiated in RA-diagnosed patients who experienced treatment failure or decreased response on the administration of conventional disease-modifying anti-rheumatic drugs. Treatment response after 1g of rituximab infusion was assessed at &lt;6 months and &gt; 6 months follow-up period using patient-reported outcome measure tools and laboratory investigations. Functional ability was evaluated using a questionnaire and the overall disability index was calculated. It was found that all patients achieved minimum clinically important difference(&gt;0.2) from baseline HAQ value within 6 months of rituximab. Assessment of the functional ability demonstrated that the majority of the patients experienced significant improvement in all domains of HAQ-DI after rituximab administration. Patient global assessment shared a moderate correlation with almost all domains of HAQ-DI. Physical function as measured by HAQ-DI showed clinically meaningful improvement within 1 year of rituximab therapy. It has proven to be a safer and more effective treatment option when compared to conventional disease-modifying antirheumatic drugs and has also helped in achieving better responses at a faster pace.

Salidroside suppresses cell growth and inflammatory response of fibroblast-like synoviocytes via inhibition of phosphoinositol-3 kinase/threonine kinase signaling in rheumatoid arthritis.

Salidroside (Sal) is anatural product commonly isolated from Rhodiola rosea L., which has been found to have numerous pharmacological activities (e.g., ameliorating apoptosis and inflammation, and acting as an antioxidant) in various diseases, but its concrete function in rheumatoid arthritis (RA) has not been revealed yet. Here, we aimed to explore the specific role and underlying mechanisms of Sal in RA-fibroblast-like synoviocytes (RA-FLSs). Cell counting kit 8 (CCK-8) was used to assess the viability of normal-FLSs and RA-FLSs. Cell apoptosis in RA-FLSs was evaluated by flow cytometry. Western blotting was prepared to examine the levels of apoptosis- and signaling-related proteins. Wound-healing and Transwell assays were conducted to examine RA-FLSs migration and invasion. Enzyme-linked immunosorbent assay (ELISA) was used to assess the effect of Sal on tumor necrosis factor-alpha (TNF-α)-induced inflammation in RA-FLSs. RA animal model was established through complete Freund's adjuvant (CFA) induction, and the histopathological changes in synovial tissues of the rat model were analyzed by H&E staining. RA-FLSs were treated with 200 μM Sal for 24 h, and cell viability was significantly suppressed. Sal promoted RA-FLSs apoptosis. The migratory and invasive abilities of RA-FLSs were markedly inhibited by Sal. Sal incubation reduced the levels of inflammatory cytokines interleukin‑8 (IL-8), IL-1β, and IL‑6 in RA-FLSs under the stimulation of TNF‑α. Subsequently, Sal downregulated phosphorylated phosphatidylinositol‑3 kinase (p-PI3K) and protein kinase (p-AKT) expression in RA-FLSs. After the treatment with pathway activator 740Y‑P (20 μM) in RA-FLSs, the promotive effect of Sal on cell apoptosis was reversed, and inhibitory effects of it on cell viability, migration, invasion, and inflammatory response were abolished. Sal inhibited RA development in the CFA-induced rat model. Sal suppressed cell growth and inflammation in RA-FLSs by inactivating PI3K/AKT-signaling pathways.

Exploring CircRNA N6-methyladenosine in human rheumatoid arthritis: Hyper-methylated hsa_circ_0007259 as a potential biomarker and its involvement in the hsa_circ_0007259/hsa_miR-21-5p/STAT3 axis

BackgroundN6-methyladenosine (m6A) is a highly enriched modification found in circular RNAs (CircRNAs); however, the ability and mechanism of CircRNAs to encode for m6A function in rheumatoid arthritis (RA) remain poorly understood. MethodsWe utilized an epitranscriptomic microarray to measure levels and quantities of m6A methylated CircRNAs in synovial tissues of patients with RA and osteoarthritis (OA). We then utilized methylated RNA immunoprecipitation- and MazF-quantitative PCR to identify and validate differentially m6A-methylated RNAs between the groups, conducted a functional enrichment analysis, and selected protein–protein interaction hub genes. Lastly, we predicted and validated the CircRNA/miRNA/mRNA interaction networks. ResultsWe detected 4,845 CircRNAs containing m6A in our samples, with 53 CircRNAs upregulated, and 139 CircRNAs downregulated compared to human OA synovial tissue (|fold change| ≥ 1.2 and p ≤ 0.05). The differentially m6A-modified CircRNAs were associated with the interleukin-6-mediated signaling pathway, with an increase in relative m6A-methylated levels of hsa_circ_0007259 in human RA, a significant decrease in hsa_miR-21-5p, and an increase in signal transducer and activator of transcription 3（STAT3）. The Luciferase Reporter Gene assay verified the binding of hsa_circ_0007259 to hsa_miR-21-5p and the subsequent binding of hsa_miR-21-5p to STAT3. ConclusionWe showed a notable increase in the relative m6A-methylated levels of hsa_circ_0007259 in human RA, indicating a potential role of hypermethylated hsa_circ_0007259 in RA pathogenesis. This may provide valuable insight into the mechanism of RA and the possibility of utilizing hsa_circ_0007259 as a valuable biomarker.

An engineered glove to follow finger function in rheumatoid arthritis: an observational prospective study

The engineered Hand Test System (HTS) glove has shown high reliability in assessing the baseline functional status of rheumatoid arthritis (RA) hand. Starting from this achievement, the aim of the present observational prospective study was to assess the functionality of the single fingers of rheumatoid hand at follow-up. Eighty RA patients performed HTS glove tests at baseline and among these fifty-six patients were re-tested after 7 months. The HTS glove parameters [Touch Duration (TD), Movement Rate (MR), Inter Tapping Interval (ITI)] were correlated with disease activity and disability clinimetric indexes [Disease Activity Score 28 joint count—C-reactive protein (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire—Disability Index (HAQ-DI), grip strength, visual analogue scale of pain (VAS), patient global assessment (PGA)], and with laboratory values. HTS glove parameters (TD, ITI, and MR) showed statistically significant correlations with clinimetric and clinical indexes at both time points (p < 0.05). During follow-up, a statistically significant variation of all HTS glove parameters for the fingers that have performed both the worst or best HTS test at baseline was detected (p < 0.05), while the mean HTS glove parameter values by considering all fingers did not show a statistically significant variation over time, as well as the traditional clinimetric indexes. Besides the objective role in assessing the RA hand function by integrating the traditional clinimetric indexes, the HTS glove seems a useful tool for evaluating worst or best finger function during time by measuring the movement speed.

Efficacy of Muscle Energy Technique (MET) for Hand Function in Rheumatoid Arthritis

Background: Rheumatoid Arthritis is a rare condition which affects only 1% population in India. It is an autoimmuneand chronic inflammatory condition which affects joints and organ system. And as it is also a progressive diseaseso medication and physiotherapy is must for stopping from further worsening of condition. This research aims tofind out efficacy of Muscle Energy Technique for hand function in rheumatoid arthritis.Methods: 50 Rheumatoid arthritis patients were chosen considering the inclusion and exclusion criteria. Thepurpose and nature of study was explained to the participants, a consent form being filled by the participants. Thestudy was carried out by taking assessment of range of motion and VAS and then the treatment regime was startedand after completing the treatment protocol assessment was taken again. The assessment which was collected wasentered into a database on Microsoft excel and word.Conclusion: Based upon the pre-post treatment assessment done and its data collection, the RA patients are proneto get their Range of Motion and Muscle Strength to get affected which also hampers their daily activities. Theawareness regarding the condition, preventive methods and even exercise protocol are very helpful in avoidingfurther risk factors.

Status of Renal and Liver Function in Rheumatoid Arthritis (RA) Patients of Chattogram, Bangladesh Treated with Methotrexate (MTX)

Status of Renal and Liver Function in Rheumatoid Arthritis (RA) Patients of Chattogram, Bangladesh Treated with Methotrexate (MTX)

Foot function in rheumatoid arthritis: Correlation between the Rheumatoid and Arthritis Outcome Score and performance-based physical tests.

Foot function is usually assessed using self-reported outcome measures which remain subjective in patients with rheumatoid arthritis (RA). Physical performance tests were recommended for functional assessment in lower limb osteoarthritis. However, foot function assessment's guidelines in RA are lacking. We aimed to investigate the correlation between a self-reported outcome measure and two performance-based physical tests for assessing foot function in RA patients. A cross-sectional study was performed over 7months' period including RA patients. We used Rheumatoid and Arthritis Outcome score (RAOS) as a self-reported functional tool. Physical performance tests were 4-min walk test (4-MWT) and Timed up and go test (TUGT). Fifty RA patients were included with 96% females and a mean age of 54.7±10.4years. Foot involvement occurred since the diagnosis of RA in 36% of patients. Foot pain was reported by 68% of patients (48% forefoot), and foot stiffness in 46% of patients. Skin lesions of the feet were found in 78% of patients, 90% had foot deformities and 56% had inflammatory disorders of feet. Radiographic lesions were found in 94% of patients. The most impaired RAOS subscales were Sports and Recreation and Quality of life. Poor physical-based performance was found in 34% of RA patients according to 4-MWT, in 42% of RA patients according TUGT, and in 46% of patients based on at least one performance test. RAOS was negatively correlated to the 4-MWT and positively correlated in the subscales pain, other symptoms, activities of daily living, and Sport/Rec of the RAOS. Poor performance-based physical tests were significantly associated with advanced age, sedentary lifestyle, higher disease activity score and impaired functional status. Foot-related parameters significantly associated with poor performance-based physical tests were: foot pain, foot deformity and inflammatory disorders. Multivariate analysis identified foot deformities and higher functional impairment as predictive factors for lower gait speed (4-MWT) and older age and higher functional impairment for higher duration of TUGT. RAOS was significantly associated with performance-based physical function. In the era of connected technologies, these results encourage the regular assessment of rheumatoid foot function by the RAOS score through a connected programme using wearable trackers.

Umbilical cord mesenchymal stem cell-derived exosomes alleviate collagen-induced arthritis by balancing the population of Th17 and regulatory T cells.

Exosomes released by mesenchymal stem cells (MSCs) are thought to function as extensions of the MSCs. However, it remains unclear whether exosomes derived from human umbilical cord MSCs (HUMSCs) possess immunoregulatory functions in rheumatoid arthritis. We report that when mice with collagen-induced arthritis were injected with exosomes derived from HUMSC (HUMSC-Exo), their paws became less swollen, and they had lower serum pro-inflammatory cytokine and anti-collagen IgG levels, and decreased synovial hyperplasia. The HUMSC-Exo appeared to restore the balance between Th17 and Treg cells, and this effect was accompanied by reduced IL-17 and enhanced TGF-β and IL-10 levels. These findings suggest that HUMSC-Exo function as important regulator of the balance between Th1/Th17 and Treg cells during immune and inflammatory responses.

Th1-Like Treg Cells Are Increased But Deficient in Function in Rheumatoid Arthritis.

ObjectivesThis study aimed to investigate the changes in quantity and function of T helper (Th)-like T regulatory (Treg) cell subsets in peripheral blood (PB) and synovial fluid (SF) of rheumatoid arthritis (RA) patients and to understand their relationship with disease activity.MethodsA total of 86 RA patients and 76 gender and age-matched healthy controls (HC) were enrolled in this study. Th-like Treg frequency and function were determined using flow cytometry. The inhibitory function of Th-like Treg cells was detected using an in vitro co-culture suppression assay.ResultsThe proportion and absolute number of Th1-like Treg cells from RA PB and RA SF were significantly higher than those of HC PB. In RA SF, the proportions of Treg cells and Th1-like Treg cells were significantly lower in the elevated erythrocyte sedimentation rate or the C-Reactive Protein group, and in the positive groups of anti-CCP antibody and anti-MCV antibody. Additionally, the proportions of Treg cells and Th1-like Treg cells from RA SF were negatively correlated with disease activity. However, the expression levels of CD73 and TGF-β1 in Th1-like Treg cells were decreased, and these Treg cells could not effectively inhibit the proliferation of effector T (Teff) cells.ConclusionOur data indicate that Th1-like Treg cells are the predominant Treg cell subset in RA SF, but their suppressive function is defective. Improving the function of Th1-like Treg cells may control inflammation in joints and provide new strategies for Treg-targeted therapies in RA.

Scale Banking for Patient-Reported Outcome Measures That Measure Functioning in Rheumatoid Arthritis: A Daily Activities Metric.

Functioning is an important outcome for the management of rheumatoid arthritis (RA). Heterogeneity of respective patient-reported outcome measures (PROMs) challenges direct comparisons between their results. This study aimed to standardize reporting of such PROMs measuring functioning in RA to facilitate comparability. Common-item nonequivalent group design with the Health Assessment Questionnaire (HAQ) as a common scale across data sets from various countries (including the UK, Turkey, and Germany) to establish a common metric was used. Other PROMs included are the physical function items of the Multidimensional HAQ (MDHAQ), the Disabilities of the Arm, Shoulder, and Hand questionnaire, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the World Health Organization Disability Assessment Schedule II (WHODAS II), the Medical Outcomes Study Short Form 36 (SF-36) health survey, and 4 short forms (20, 10, 6, and 4 physical function items) from the Patient-Reported Outcomes Measurement Information System. As the HAQ includes mobility, self-care, and domestic life items, this study focuses on these 3 domains. PROMs were described using standard error of measurement (SEM) and smallest detectable difference (SDD). A Rasch measurement model was used to create the common metric. The range of the SEM was 0.2 (MDHAQ) to 7.4 (SF-36 health survey physical functioning domain). The SDD revealed a range from 9.7% (WOMAC rating scale) to 33.5% (WHODAS physical functioning domain). PROMs co-calibration revealed fit to the Rasch measurement model. A transformation table was developed to allow exchange between PROM scores. Scores between the daily activity PROMs commonly used in RA can now be compared. Factors such as SEM and SDD help to determine the choice of a PROM in clinical practice and research.

Circulating Biomarkers and Cardiac Structure and Function in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) increases the risk for abnormalities of the cardiac structure and function, which may lead to heart failure (HF). Studying the association between circulating biomarkers and echocardiographic parameters is important to screen patients with RA with a higher risk of cardiac dysfunction.Aim: To study the association between circulating biomarkers and echocardiographic parameters in patients with RA.Methods: Echocardiography was performed in 355 patients with RA from RA Porto cohort and the associations between echocardiographic characteristics and 94 circulating biomarkers were assessed. These associations were also assessed in the Metabolic Road to Diastolic Heart Failure (MEDIA-DHF) [392 patients with HF with preserved ejection fraction (HFpEF)] and the Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) (1,672 healthy population) cohorts.Results: In the RA Porto cohort, mean age was 58 ± 13 years, 23% were males and mean RA duration was 12 ± 10 years. After adjustment and multiple testing correction, left ventricular mass index (LVMi), left atrial volume index (LAVi), and E/e′ were independently associated with biomarkers reflecting inflammation [i.e., bone morphogenetic protein 9 (BMP9), pentraxin-related protein 3 (PTX3), tumor necrosis factor receptor superfamily member 11a (TNFRSF11A)], extracellular matrix remodeling [i.e., placental growth factor (PGF)], congestion [i.e., N-terminal pro-brain natriuretic peptide (NT-proBNP), adrenomedullin (ADM)], and myocardial injury (e.g., troponin). Greater LVMi [hazard ratio (HR) (95% CI) per 1 g/m2 = 1.03 (1.02–1.04), p < 0.001], LAVi [HR (95% CI) per 1 ml/m2 = 1.03 (1.01–1.06), p < 0.001], and E/e′ [HR (95% CI) per 1 = 1.08 (1.04–1.13), p < 0.001] were associated with higher rates of cardiovascular events. These associations were externally replicated in patients with HFpEF and asymptomatic individuals.Conclusion: Circulating biomarkers reflecting inflammation, extracellular matrix remodeling, congestion, and myocardial injury were associated with underlying alterations of cardiac structure and function. Biomarkers might be used for the screening of cardiac alterations in patients with RA.

Patterns of Anti-Inflammatory and Immunomodulating Drug Usage and Microvascular Endothelial Function in Rheumatoid Arthritis

Objectives: Specific anti-inflammatory and/or immunomodulating drugs (AIDs) can influence endothelial function which is often impaired in patients with rheumatoid arthritis (RA). We sought to determine whether overall patterns of AID usage are similarly associated with endothelial function.Methods: The reactive hyperaemia index (RHI), a marker of microvascular endothelial function, was measured in 868 RA patients reporting their intake of seven AIDs known to affect endothelial function. Latent class analysis (LCA) was performed to characterise patterns of AID usage. Models for 2–6 classes were compared using the AIC and BIC statistics and Lo-Mendell-Rubin likelihood ratio tests. Associations between the classes and RHI were adjusted for age, gender, body mass index, diabetes, HDL-cholesterol, LDL-cholesterol, family history of ischaemic heart disease, smoking status, RA duration, DAS28 score, steroid dose, existing hypertension, and C-reactive protein.Results: LCA identified five distinct AID usage classes: Class 1, generally low medication usage; Class 2, using either sulfasalazine or non-tumour necrosis factor (TNF) inhibitors; Class 3, methotrexate users; Class 4, TNF-inhibitor users; and Class 5, hydroxychloroquine users. The geometric mean for the RHI for subjects in classes 1 to 5 was 1.92, 1.81, 1.94, 2.10, and 2.07, respectively, with subjects in classes 4 and 5 having better endothelial function than subjects in class 2 (p = 0.003 for each). The glucocorticoid dosage did not influence the classes formed or the association between the classes and the RHI in sensitivity analyses.Conclusion: There were five broad patterns (classes) of AID usage in RA patients. The RHI was relatively lower in users of either sulfasalazine or non-TNF inhibitors. TNF inhibitors or hydroxychloroquine may counteract the negative effects of RA on endothelial function.

Loss of \u03b12-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in arthritis

In healthy joints, synovial fibroblasts (SFs) provide the microenvironment required to mediate homeostasis, but these cells adopt a pathological function in rheumatoid arthritis (RA). Carbohydrates (glycans) on cell surfaces are fundamental regulators of the interactions between stromal and immune cells, but little is known about the role of the SF glycome in joint inflammation. Here we study stromal guided pathophysiology by mapping SFs glycosylation pathways. Combining transcriptomic and glycomic analysis, we show that transformation of fibroblasts into pro-inflammatory cells is associated with glycan remodeling, a process that involves TNF-dependent inhibition of the glycosyltransferase ST6Gal1 and α2-6 sialylation. SF sialylation correlates with distinct functional subsets in murine experimental arthritis and remission stages in human RA. We propose that pro-inflammatory cytokines remodel the SF-glycome, converting the synovium into an under-sialylated and highly pro-inflammatory microenvironment. These results highlight the importance of glycosylation in stromal immunology and joint inflammation.

Association of Low Muscle Density With Deteriorations in Muscle Strength and Physical Functioning in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with low muscle density due to the accumulation of intramuscular fat. The present study was undertaken to identify predictors of changes in muscle density and to determine whether low muscle density predicted changes in strength and physical function. Patients with RA, ages 18-70 years, completed whole-body dual-energy x-ray absorptiometry and peripheral quantitative computed tomography to quantify lean and fat mass indices and muscle density. Dynamometry was used to measure strength at the hand, knee, and lower leg. Disability and physical function were measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). Assessments were performed at baseline and at follow-up. Regression analyses assessed associations between patient characteristics, muscle density, and deteriorations in strength and function. Muscle density was assessed at baseline in 107 patients with RA. Seventy-nine of these patients (74%) returned for a follow-up assessment at a median follow-up time of 2.71 years (interquartile range 2.35-3.57). Factors associated with declines in muscle density included female sex, higher disease activity, smoking, and lower insulin-like growth factor 1 (IGF-1) levels. Greater muscle density Z score at baseline (per 1 SD) was associated with less worsening per year according to HAQ, SPPB, and 4-meter walk time scores and a lower risk of a clinically important worsening in HAQ score (odds ratio [OR] 1.90 [95% confidence interval (95% CI) 1.06, 3.42]; P = 0.03) and walking speed (OR 2.87 [95% CI 1.05, 7.89]; P = 0.04). Worsening of skeletal muscle density occurred in patients with higher disease activity, in smokers, and in those with lower IGF-1. Low muscle density was associated with worsening of physical function. Interventions addressing reductions in muscle quality might prevent functional decline.

Effects of Yoga in Daily Life program in rheumatoid arthritis: A randomized controlled trial

ObjectivesTo explore the feasibility and effectiveness of a yoga program in improving health-related quality of life (HQOL), physical and psychological functioning in rheumatoid arthritis (RA) patients. DesignSingle-centre parallel-arms randomized controlled trial comparing yoga (n = 30) and education control group (n = 27). SettingTertiary care University hospital. InterventionA 12-week yoga program, based on the Yoga in Daily Life system, included 2x weekly/90-minute sessions. The control group had 1xweekly/60-minute educational lectures on arthritis-related topics. Main outcome measuresAssessments were performed at baseline, 12 (post-intervention) and 24 weeks (follow-up). The primary outcome was change in The Short Form-36 (SF-36) HQOL at 12 weeks. Linear regression analysis was adjusted for baseline scores. ResultsNo significant between-group differences were found for SF-36 (all p > 0.05). At 12 weeks the adjusted mean difference between groups favoured yoga for Functional Assessment of Chronic Illness Therapy-fatigue (5.08 CI 1.29 to 8.86; p = 0.009) and Hospital Anxiety and Depression Scale (HADS)-depression (−1.37 CI −2.38 to −0.36); p = 0.008) and at 24 weeks for HADS-anxiety (−1.79 CI −3.34 to − 0.23; p = 0.025), while the impact on fatigue was sustained (5.43 CI 1.33 to 9.54, p = 0.01). The program had no impact on RA disease activity. Feasibility outcomes included recruitment rate 16 %, retention 80.7 %, and adherence to yoga 87.5 vs 82.7 % for control. No serious adverse events were recorded. ConclusionsYoga in Daily Life program was not associated with change in health-related quality of life of RA patients. Significant improvements in fatigue and mood were observed at postintervention and follow-up. This yoga program was found feasible and safe for patients and may complement standard RA treat-to-target strategy.