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ID PMID Title PublicationDate abstract
31267798 Ankle kinematics and kinetics during gait in healthy and rheumatoid arthritis post-menopau 2019 Jun Objective: In the literature, it is not clear whether rheumatoid arthritis (RA) post-menopausal women have different ankle biomechanical parameters than healthy post-menopausal women. This study aimed to compare the ankle kinematics and kinetics during the gait stance phase of RA post-menopausal women with age-matched healthy post-menopausal women. Materials and methods: A three-dimensional motion analysis system (9 cameras; 200 Hz) synchronised with a force plate (1000 Hz) was used to assess ankle kinematics and kinetics during barefoot walking at a natural and self-selected speed. A biomechanical model was used to model body segments and joint centres (combined anthropometric measurements and the placement of 39 reflective markers). Thirty-six women (18 RA post-menopausal women and 18 age-matched healthy post-menopausal women) performed 14 valid trials (comprising seven left and seven right footsteps on a force plate). Lower limb muscle mass was evaluated by an octopolar bioimpedance analyser. Results: RA post-menopausal women yielded a longer stance phase and controlled dorsiflexion sub-phase (p < 0.001), higher dorsiflexion at the final controlled dorsiflexion sub-phase and lower plantar flexion at toe off (p < 0.05), lower angular displacements (p < 0.05), and lower ankle moment of force peak and ankle power peak (p < 0.001). No intergroup differences were found in lower limb muscle mass. Conclusions: RA post-menopausal women yielded changes in ankle kinematic and kinetic parameters during the gait stance phase, resulting in a lower capacity to produce ankle moment of force and ankle power during the propulsive gait phase.
30328699 Effectiveness of Acupuncture on Pain, Functional Disability, and Quality of Life in Rheuma 2019 Jan BACKGROUND: Rheumatoid arthritis (RA) is characterized by pain, functional disability, poor quality of life (QoL), high socioeconomic impact, and annual costs of over $56 billion in the United States. Acupuncture (AC) is widely in use; however, studies show severe methodological shortcomings, did not consider the functional diagnosis for the allocation of acupoints and their results showed no differences between verum and control groups. OBJECTIVE: The authors aimed to objectively assess the safety and efficacy of AC treatments for RA. METHODS: 105 RA patients with a functional diagnosis of a "Pivot syndrome" or "Turning Point syndrome" were randomly assigned to (1) verum-AC (verum acupoints), (2) control-AC (sham acupoints-points outside of the conduits/meridians and of the extra-conduits), or (3) waiting list (each group n = 35). AC groups experienced the exact same number, depth, and stimulation of needles. Assessments took place before and 5 min after AC with follow-ups over 4 weeks. RESULTS: (1) Verum-AC significantly improved self-reported pain (Z = -5.099, p < 0.001) and pressure algometry (Z = -5.086, p < 0.001); hand grip strength (Z = -5.086, p < 0.001) and arm strength (Z = -5.086, p < 0.001); health status improved significantly (p < 0.001, Z = -4.895); QoL improved significantly in 7/8 survey domains; and number of swollen joints (Z = -2.862, p = 0.004) and tender joints (Z = -3.986, p < 0.001) significantly decreased. (2) Control-AC showed no significant changes, except in self-reported pain improvement. (3) Waiting list group showed an overall worsening. CONCLUSION: This is the first double-blind controlled study on AC in RA of the hand that objectively and specifically assesses positive effects supporting its integration in rheumatology. Acupoint allocation according to Chinese Medicine functional diagnoses is extremely relevant to assess AC effectiveness in a patient group primarily defined by a "western" medicine diagnosis. Based on clear allocation criteria for acupoints, the authors minimized the possible bias of unspecific and suggestive effects on the control group, showed the specific effects of the points chosen, improved efficacy, and identified an evidence base for AC.
31659869 Association of adipokines with rheumatic disease activity indexes and periodontal disease 2019 Nov OBJECTIVE: To evaluate the adipokine levels in early rheumatoid arthritis (eRA) and first-degree relatives (FDR) of patients with RA and establish their association with rheumatic disease activity and periodontal variables. METHOD: A cross-sectional study with eRA patients, FDR and a healthy population. Adipokine levels, clinical, joint radiological indexes and periodontal variables were evaluated. A descriptive, bivariate analysis was performed based on the adipokine levels by χ(2) , Fisher's test and Mann-Whitney U test. A logistic regression was made for associations. RESULTS: High leptin levels were associated with the diagnosis of eRA (odds ratio [OR] = 2.79; 95% CI 1.54-5.07). Early rheumatoid arthritis with high adiponectin levels was less likely to have Multidimensional Health Assessment Questionnaire score >3, body mass index (BMI) >25 and Routine Assessment of Patient Index Data 3 score >12 (OR = 0.16; 95% CI 0.03-0.72). Early rheumatoid arthritis was more likely to present high leptin and interleukin (IL)6 levels with low adiponectin simultaneously (OR = 5.03; 95% CI 1.05-24.0). High leptin levels were associated with the FDR adjusted for IgG2 Porphyromonas gingivalis, swollen joints, P gingivalis and low IL6 (OR = 2.57; 95% CI 1.14-5.95). CONCLUSION: High adipokine levels in eRA may modulate the disease activity. Having more than 1 adipokine at high serum levels is associated with increased disability, disease activity and BMI, indicating that RA is controlled by adiponectin levels in the early stages of the disease. High leptin levels, presence of P gingivalis and swollen joints may be the factors associated with the development of RA in FDR.
30611306 Altered composition and phenotype of mucosal-associated invariant T cells in early untreat 2019 Jan 5 BACKGROUND: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognise bacterial metabolites presented by MHC class I-related protein 1 (MR1). Bacterial dysbiosis has been implicated in auto-inflammatory disease development. We investigated MAIT cells in early, untreated rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients. METHODS: Blood and synovial fluid mononuclear cells obtained from patients (SpA/RA) and controls were stimulated with fixed Escherichia coli to provide MAIT ligand. Cells were analysed by flow cytometry and MAIT cells were identified by MR1-5-OP-RU tetramers. Synovial biopsies were studied by confocal microscopy. RESULTS: Peripheral and synovial CD3(+) MR1-tet(+) MAIT cell frequencies were comparable in all groups. MAIT cells were detected in RA and SpA synovium based on CD3, CD161 and Vα7.2 expression. Peripheral RA MAIT cells were mostly CD4(+) (controls 8.3%, SpA 12.3%, RA 52.6%; p < 0.001) and CD161 expression was strongly reduced (control mean fluorescence intensity (MFI) = 2348, SpA MFI = 2219, RA MFI = 226; p < 0.001). MAIT cells were hyporesponsive, shown by minimal upregulation of CD25 and CD69 to E. coli stimulation (control, CD25 MFI = 177, CD69 MFI = 1307; SpA, CD25 MFI = 95, CD69 MFI = 1257; RA, CD25 MFI = 0, CD69 MFI = 467; p < 0.001 and p = 0.01 respectively). CONCLUSION: In early untreated RA patients, the peripheral MAIT cell composition was altered, with reduced levels of CD161 expression, and cells were hyporesponsive to stimulation. MAIT cell dysfunction may provide a link between the microbiome and development of RA.
31174578 Depletion of activated macrophages with a folate receptor-beta-specific antibody improves 2019 Jun 7 OBJECTIVES: Most therapies for autoimmune and inflammatory diseases either neutralize or suppress production of inflammatory cytokines produced by activated macrophages (e.g., TNFα, IL-1, IL-6, IL-17, GM-CSF). However, no approved therapies directly target this activated subset of macrophages. METHODS: First, we undertook to examine whether the folate receptor beta (FR-β) positive subpopulation of macrophages, which marks the inflammatory subset in animal models of rheumatoid arthritis, might constitute the prominent population of macrophages in inflamed lesions in humans. Next, we utilized anti-FR-β monoclonal antibodies capable of mediating antibody-dependent cell cytotoxicity (ADCC) to treat animal models of rheumatoid arthritis and peritonitis. RESULTS: Human tissue samples of rheumatoid arthritis, Crohn's disease, ulcerative colitis, idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, chronic obstructive pulmonary disease, systemic lupus erythematosus, psoriasis, and scleroderma are all characterized by dramatic accumulation of macrophages that express FR-β, a protein not expressed on resting macrophages or any other healthy tissues. A monoclonal antibody to FR-β accumulates specifically in inflamed lesions of murine inflammatory disease models and successfully treats such models of rheumatoid arthritis and peritonitis. More importantly, elimination of FR-β-positive macrophages upon treatment with an anti-FR-β monoclonal antibody promotes the departure of other immune cells, including T cells, B cells, neutrophils, and dendritic cells from the inflamed lesions. CONCLUSIONS: These data suggest that specific elimination of FR-β-expressing macrophages may constitute a highly specific therapy for multiple autoimmune and inflammatory diseases and that a recently developed human anti-human FR-β monoclonal antibody (m909) might contribute to suppression of this subpopulation of macrophages.
31829260 Improved RA classification among early arthritis patients with the concordant presence of 2019 Dec 11 BACKGROUND: The patients with RA benefit from early identification soon after the first clinical symptoms appear. The 2010 ACR/EULAR classification criteria were developed to fulfill this need and their application has been demonstrated to be effective. However, there is still room for improvement. Therefore, we aimed to evaluate the potential of the concordant presence of RF, anti-CCP and anti-carbamylated protein antibodies to improve current RA classification among early arthritis (EA) patients. METHODS: Data from the first visit of 1057 patients in two EA prospective cohorts were used. The serological scores from the 2010 ACR/EULAR criteria and the concordant presence of the three RA autoantibodies were assessed relative to a gold standard consisting of the RA classification with the 1987 ACR criteria at the 2 years of follow-up. RESULTS: The concordant presence of three antibodies showed predictive characteristics allowing for direct classification as RA (positive predictive value = 96.1% and OR = 80.9). They were significantly better than the corresponding to the high antibody titers defined as in the 2010 classification criteria (PPV = 88.8%, OR = 26.1). In addition, the concordant presence of two antibodies was also very informative (PPV = 82.3%, OR = 15.1). These results allowed devising a scoring system based only on antibody concordance that displayed similar overall performance as the serological scoring system of the 2010 criteria. However, the best classification was obtained combining the concordance and 2010 serological systems, a combination with a significant contribution from each of the two systems. DISCUSSION: The concordant presence of RA autoantibodies showed an independent contribution to the classification of EA patients that permitted increased discrimination and precision.
31288799 Chronic obstructive pulmonary disease in rheumatoid arthritis: a systematic review and met 2019 Jul 9 BACKGROUND: The risk and prevalence of chronic obstructive pulmonary disease (COPD) in rheumatoid arthritis (RA) is still obscure. The current study was aimed to systematically review and meta-analyse the risk ratio (RR) and prevalence of COPD in RA. METHODS: A comprehensive systematic review was conducted based on PubMed, Web of Science and Cochrane Library from inception to April 30, 2018. The primary outcome of our study was the RR of COPD in RA patients compared with controls, and secondary was the prevalence of COPD in RA patients. Pooled effect sizes were calculated according to fixed effect model or random effects model depending on heterogeneity. RESULTS: Six and eight studies reported the RR and prevalence of COPD in RA respectively. Compared with controls, RA patients have significant increased risk of incident COPD with pooled RR 1.82 (95% CI = 1.55 to 2.10, P <  0.001). The pooled prevalence of COPD in RA patients was 6.2% (95% CI = 4.1 to 8.3%). Meta-regression identified that publication year was an independent covariate negatively associated with the RR of COPD, and smoker proportion of RA population was also positively associated with the prevalence of COPD significantly in RA patients. CONCLUSIONS: The present meta-analysis has demonstrated the significant increased risk and high prevalence of COPD in RA patients. Patients with RA had better cease tobacco use and rheumatologists should pay attention to the monitoring of COPD for the prevention and control of COPD.
31346705 [Establishment of the current classification criteria for axial spondylarthritis, rheumato 2019 Dec BACKGROUND: In Germany, the numbers of patients with spondylarthritides (SpA) and rheumatoid arthritis (RA) have increased. This rise was possibly promoted by the introduction of new classification criteria (CC) that enable an earlier recognition and the inclusion of less severe cases. The study explores how the new CC for axial SpA (axSpA) are incorporated into the clinical practice, compared with the CC for RA and systemic lupus erythematosus (SLE). In addition, the study investigated whether the new entity of non-radiographic axSpA (nr-axSpA) is accepted and used in Germany. MATERIAL AND METHODS: In 2016, an online survey was performed among all rheumatologists registered in the German Society of Rheumatology (DGRh). In addition, 150 rheumatologists were invited to the survey at the national meeting of the DGRh in 2016. RESULTS: Among 119 participating rheumatologists, 99% were familiar with the new CC for SpA and 82% applied them in practice (RA 99% and 80%, SLE 50% and 56%). 78% differentiated between radiographic and nr-axSpA and 80% believed that a significant proportion of patients with nr-axSpA will never develop radiographic changes. 91% agreed that the new CC facilitated an earlier treatment start and 58% that the CC enabled more patients to receive biologicals. 50% shared the opinion that the criterion "chronic back pain" could lead to the classification of too many patients as having axSpA. It deemed possible to 65% that patients with nr-axSpA would be treated with biologicals in whom the diagnosis of axSpA could not be confirmed later on. 81% voted against the initiation of TNF inhibitors in nr-axSpA patients with normal CRP levels and normal MRI. 67% interpreted the MRI themselves and 30% stated that the MRI is evaluated according to validated standards by the radiologists. Among all axSpA criteria, HLA B27 and inflammatory back pain received the highest significance and the response to NSAID the lowest. CONCLUSION: The new CC and the entity of nr-axSpA are accepted by German rheumatologists. A relevant proportion saw weaknesses of the new CC in the differentiation between nr-axSpA and non-specific chronic back pain. In practise, the interpretation of the CC with respect to the start of biologics is relatively strict, especially in cases with normal CRP and MRI. A ranking of axSpA criteria is commonly applied, although this was not initially intended in the CC.
31097419 TNF-induced inflammatory genes escape repression in fibroblast-like synoviocytes: transcri 2019 Sep OBJECTIVE: We investigated genome-wide changes in gene expression and chromatin remodelling induced by tumour necrosis factor (TNF) in fibroblast-like synoviocytes (FLS) and macrophages to better understand the contribution of FLS to the pathogenesis of rheumatoid arthritis (RA). METHODS: FLS were purified from patients with RA and CD14(+) human monocyte-derived macrophages were obtained from healthy donors. RNA-sequencing, histone 3 lysine 27 acetylation (H3K27ac), chromatin immunoprecipitation-sequencing (ChIP-seq) and assay for transposable accessible chromatin by high throughput sequencing (ATAC-seq) were performed in control and TNF-stimulated cells. RESULTS: We discovered 280 TNF-inducible arthritogenic genes which are transiently expressed and subsequently repressed in macrophages, but in RA, FLS are expressed with prolonged kinetics that parallel the unremitting kinetics of RA synovitis. 80 out of these 280 fibroblast-sustained genes (FSGs) that escape repression in FLS relative to macrophages were desensitised (tolerised) in macrophages. Epigenomic analysis revealed persistent H3K27 acetylation and increased chromatin accessibility in regulatory elements associated with FSGs in TNF-stimulated FLS. The accessible regulatory elements of FSGs were enriched in binding motifs for nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interferon-regulatory factors (IRFs) and activating protein-1 (AP-1). Inhibition of bromodomain and extra-terminal motif (BET) proteins, which interact with histone acetylation, suppressed sustained induction of FSGs by TNF. CONCLUSION: Our genome-wide analysis has identified the escape of genes from transcriptional repression in FLS as a novel mechanism potentially contributing to the chronic unremitting synovitis observed in RA. Our finding that TNF induces sustained chromatin activation in regulatory elements of the genes that escape repression in RA FLS suggests that altering or targeting chromatin states in FLS (eg, with inhibitors of BET proteins) is an attractive therapeutic strategy.
30878554 Fighting rheumatoid arthritis: Kv1.3 as a therapeutic target. 2019 Jul Rheumatoid arthritis (RA) is a serious autoimmune disease that has severe impacts on both the wellbeing of patients and the economy of the health system. Similar to many autoimmune diseases, RA concurs with a long evolution, which eventually results in highly debilitating symptoms. Therapeutic treatments last for long periods during RA. However, their efficiency and side effects result in suboptimal conditions. Therefore, the need for specific, safer and nontoxic alternatives for the treatment of RA is essential. Kv1.3 is a voltage-gated potassium channel that has a crucial role in immune system response. The proliferation and activation of leukocytes are linked to differential expressions of this channel. The evidence is particularly relevant in the aggressive T effector memory (T(EM)) cells, which are the main actors in the development of autoimmune diseases. Blockage of Kv1.3 inhibits the reactivity of these cells. Furthermore, pharmacological inhibition of Kv1.3 ameliorates symptoms in animal models of autoimmune diseases, such as experimental autoimmune encephalomyelitis or induced psoriasis with no side effects. Kv1.3 is sensitive to several animal toxins and plant compounds, and several research groups have searched for new Kv1.3 blockers by improving these natural molecules. The research is mainly focused on enhancing the selectivity of the blockers, thereby reducing the potential for side effects on other related channel subunits. Higher selectivity means that treatments will potentially be less harmful. This leads to a lower discontinuation rate of the therapy than the current first-line treatment for RA. The molecular backgrounds of many autoimmune diseases implicate leukocyte Kv1.3 and suggests that a new medication for RA is feasible. Therapies could also be later repurposed to treat other immune system disorders.
30514198 Identification of Expressed miRNAs in Human Rheumatoid Arthritis Using Computational Appro 2019 BACKGROUND: Rheumatoid Arthritis (RA) is a chronic inflammatory and autoimmune disease leading to bones and joints destruction. It is one of the major causes of lifetime disability and mortality among humans in the developing and developed countries. It was evident that epigenetic dysregulation is related to the pathogenesis of RA. MicroRNAs (miRNAs) are small non-coding RNAs that are epigenetic regulators for diverse biological processes and also provided novel molecular insights in the formation of arthritis. OBJECTIVE: The influences of miRNAs in the alteration of gene regulation during the pathogenesis of arthritis were exposed in recent years. METHOD: The computational approach to identify miRNA through EST-based homology is more powerful, economical and time-efficient. In this study, we applied EST-based homology search to identify miRNAs responsible for the development of arthritis in human beings. RESULTS: Our study on 36519 ESTs in human RA condition revealed the expression of four miRNAs, HSA-miR-198, HSA-miR-4647, has-miR-7167-5p and has-miR-7167-3p. The present study is the first report about has-miR-7167 that was homologous to Macaca mulatta. CONCLUSION: The predicted targets of these identified miRNAs revealed many biological functions in the pathogenesis of RA. Further elaborated studies on these miRNAs will help to understand their function in the development of RA and the use of miRNAs as therapeutic targets in the future.
31209709 Assessment of hemostatic disturbances in women with established rheumatoid arthritis. 2019 Nov OBJECTIVES: This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. METHOD: Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. RESULTS: The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients. CONCLUSIONS: Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting. Key Points • Extensive assessment points towards persistent coagulation activation in premenopausal women with established rheumatoid arthritis. • Impaired thrombin generation and fibrin formation are associated with menopause in healthy women, while rheumatoid arthritis closes the gap within patients regarding menopause. • Fibrin morphology is unfavorably altered and fibrinolysis is decreased in patients with established rheumatoid arthritis. • Increased activity of thrombin activatable fibrinolysis inhibitor (TAFI) may contribute to impaired fibrinolysis in patients with rheumatoid arthritis.
31297977 Sustained clinical remission of rheumatoid arthritis and its predictive factors in an unse 2019 Sep AIM: To investigate the prevalence and predictors of sustained remission (SR) in an unselected Chinese rheumatoid arthritis (RA) population. PATIENTS AND METHODS: Medical records of RA patients from 2009 to 2016 were retrospectively reviewed. Clinical remission was defined according to Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and Boolean criteria. Remission persisting for at least 6 months was regarded as SR (6-month SR). Kaplan-Meier method and Cox regression analyses were performed to plot cumulative possibility of achieving 6-month SR and to identify predictors. RESULTS: Seven hundred and seventy-nine patients contributing 7958 clinic visits were included. During the follow-up period, nearly half of patients achieved 6-month SR according to DAS28-ESR (51.6%), CDAI (45.6%), SDAI (44.0%), as well as Boolean definitions (42.4%). Median time periods to 6-month SR were respectively 20.5, 28.7, 30.6, and 32.9 months based on the above criteria. Specifically, 29.4% to 41.2% of patients achieved 6-month SR at least once in the first year of follow-up, depending on instruments. Multivariate Cox regression indicated that increasing age, longer disease duration, higher baseline disease activity were independently correlated with reduced possibility of 6-month SR assessed by nearly all definitions. Conversely, male, early RA, disease-modifying antirheumatic drug-naïve and lower disease activity scores in remission measured by corresponding criteria positively contributed to SR. Importantly, treat-to-target (T2T) adherence therapy and shorter time to remission were identified as stable determinants of SR across all definitions. CONCLUSIONS: Achieving 6-month SR was not uncommon in daily practice. Male, early RA, treatment-naïve, T2T application, shorter time to remission, and lower disease activity scores in remission increased the occurrence of SR, while increasing age, longer disease duration, and higher baseline disease activity reduced the chance of remission sustainability.
29852297 The human CSF pain proteome. 2019 Jan 6 Chronic pain represents one of the major medical challenges in the 21st century, affecting >1.5 billion of the world population. Overlapping and heterogenous symptoms of various chronic pain conditions complicate their diagnosis, emphasizing the need for more specific biomarkers to improve the diagnosis and understand the disease mechanisms. We have here investigated proteins found in human CSF with respect to known "pain" genes and in a cohort of patients with dysfunctional pain (fibromyalgia, FM), inflammatory pain (rheumatoid arthritis patients, RA) and non-pain controls utilized semi-quantitative proteomics using mass spectrometry (MS) to explore quantitative differences between these cohorts of patients. We found that "pain proteins" detected in CSF using MS are typically related to synaptic transmission, inflammatory responses, neuropeptide signaling- and hormonal activity. In addition, we found ten proteins potentially associated with chronic pain in FM and RA: neural cell adhesion molecule L1, complement C4-A, lysozyme C, receptor-type tyrosine-protein phosphatase zeta, apolipoprotein D, alpha-1-antichymotrypsin, granulins, calcium/calmodulin-dependent protein kinase type II subunit alpha, mast/stem cell growth factor receptor Kit, prolow-density lipoprotein receptor-related protein 1. These proteins might be of importance for understanding the mechanisms of dysfunctional/inflammatory chronic pain and also for use as potential biomarkers. SIGNIFICANCE: Chronic pain is a common disease and it poses a large burden on worldwide health. Fibromyalgia (FM) is a heterogeneous disease of unknown etiology characterized by chronic widespread pain (CWP). The diagnosis and treatment of FM is based on the analysis of clinical assessments and no measurable biomarkers are available. Cerebrospinal fluid (CSF) has been historically considered as a rich source of biomarkers for diseases of nervous system including chronic pain. Here, we explore CSF proteome of FM patients utilizing mass spectrometry based quantitative proteomics method combined with multivariate data analysis in order to monitor the dynamics of the CSF proteome. Our findings in this exploratory study support notable presence of pain related proteins in CSF yet with specific domains including inflammatory responses, neuropeptide signaling- and hormonal activity. We have investigated molecular functions of significantly altered proteins and demonstrate presence of 176 known pain related proteins in CSF. In addition, we found ten proteins potentially associated with pain in FM and RA: neural cell adhesion molecule L1, complement C4-A, lysozyme C, receptor-type tyrosine-protein phosphatase zeta, apolipoprotein D, alpha-1-antichymotrypsin, granulins, calcium/calmodulin-dependent protein kinase type II subunit alpha, mast/stem cell growth factor receptor Kit, prolow-density lipoprotein receptor-related protein 1. These proteins are novel in the context of FM but are known to be involved in pain mechanisms including inflammatory response and signal transduction. These results should be of clear significance and interest for researchers and clinicians working in the field of pain utilizing human CSF and MS based proteomics.
30295435 Chronic Inflammation in Rheumatoid Arthritis and Mediators of Skeletal Muscle Pathology an 2019 Feb This review focuses on the effects of chronic systemic inflammation on skeletal muscle and its downstream effect on physical function in individuals with rheumatoid arthritis (RA). The importance of skeletal muscle in the regulation of whole-body glucose and lipid metabolism, and the benefits and barriers to physical activity and exercise training are highlighted. Finally, we identify knowledge gaps that may be important for the development of both pharmacologic and non-pharmacologic interventions (e.g. proper exercise regimens) to protect individuals with RA from physical impairment.
30442831 Rheumatoid Arthritis-Interstitial Lung Disease in the United States: Prevalence, Incidence 2019 Apr OBJECTIVE: Interstitial lung disease (ILD) is commonly associated with rheumatoid arthritis (RA) and can have significant morbidity and mortality. The objective of this study was to calculate the prevalence, incidence, healthcare costs, and mortality of RA-related ILD (RA-ILD) in the United States. METHODS: This retrospective cohort analysis used the Truven Health MarketScan Commercial and Medicare Supplemental health insurance databases from 2003 to 2014 and the Social Security Administration death database. Patients with RA-ILD were selected based on diagnoses on medical claims. Outcomes were 1-year prevalence and incidence of RA-ILD among the general enrollee population, all-cause and respiratory-related healthcare costs (2014 US$), and all-cause survival for a subset of newly diagnosed patients with vital status information. This analysis was descriptive. No statistical testing was conducted. RESULTS: Prevalence of RA-ILD ranged from 3.2 to 6.0 cases per 100,000 people across the 10-year period and incidence ranged from 2.7 to 3.8 cases per 100,000 people. There were 750 incident patients with 5 years of followup data. Over that time, 72% had an inpatient admission and 76% had an emergency room visit. Mean total 5-year costs were US$173,405 per patient (SD $158,837). Annual per-patient costs were highest in years 1 and 5. At 5 years after first diagnosis in the data, 35.9% of patients had died. CONCLUSION: Prevalence of RA-ILD increased over time. For patients who could be followed over a 5-year period, healthcare use and costs were somewhat stable over time, but were substantial. RA-ILD is associated with decreased survival.
30700865 Treat-to-target in rheumatoid arthritis - are we there yet? 2019 Mar Treat-to-target has been established as a guiding principle for the treatment of rheumatoid arthritis (RA) and encompasses several distinct elements: choosing a target and a method for measuring it; assessing the target at a pre-specified time point; a commitment to change the therapy if the target is not achieved; and shared decision-making. A treat-to-target approach yields superior outcomes to standard care in RA, and the ACR, EULAR and other professional organizations have endorsed treat-to-target as a fundamental therapeutic strategy for RA. Nevertheless, data on the degree to which treat-to-target is employed in the clinic are scarce; it seems that although some elements of treat-to-target are widely used, full implementation remains uncommon. Outstanding knowledge gaps to be addressed include how to select the right target for each patient, how often to assess whether the target has been achieved and the selection of each subsequent therapy in an evidence-based manner.
32044248 Evaluation and monitoring of established rheumatoid arthritis. 2019 Oct Established rheumatoid arthritis (RA) is a term used to distinguish patients with longer disease duration versus early RA or undifferentiated arthritis that may progress to RA. Although, there is no uniform definition for early disease, a cut-off of 2 years is used in most clinical trials and observational studies. In the evaluation of established RA, clinicians should incorporate a comprehensive set of measures addressing: (1) disease activity, especially inflammation that may benefit of intensification of therapy, (2) health status, (3) comorbidities, and (4) damage. Ideally, measures should include the patient and physician perspectives and be feasible, reliable, valid and sensitive to change. Traditionally, measures have been incorporated in clinical research, but it would be worthwhile to integrate them into routine care. Data collection systems adapted to rheumatologists needs, could advance care for individual patients and facilitate large observational studies to evaluate interventions for the whole spectrum of RA.
31339061 Effects of Education About Rheumatoid Arthritis and Sexuality on the Sexual Problems of Wo 2020 Mar The present quasi-experimental study was conducted to determine the effects of education about rheumatoid arthritis (RA) and sexuality on the sexual problems of women with RA. The study included 103 women with RA (51 in the experimental group, 52 in the control group). The study data were collected using the Personal Information Form and Female Sexual Function Index (FSFI). The women in the experimental group were provided education on sexuality, while those in the control group received no intervention. The aforementioned scales were administered twice: during the recruitment visit and then 1 month after the intervention. In the second measurement, the mean FSFI score increased in the experimental group, but was low in the control group, with the differences between the two groups being significant. Thus, providing sexual education to women with RA was effective in reducing sexual problems in women.
31651077 Metabolomic Profiling to Identify Molecular Biomarkers of Cellular Response to Methotrexat 2020 Jan Variation in methotrexate (MTX) efficacy represents a significant barrier to early and effective disease control in the treatment of autoimmune arthritis. We hypothesize that the utilization of metabolomic techniques will allow for an improved understanding of the biochemical basis for the pharmacological activity of MTX, and can promote the identification and evaluation of novel molecular biomarkers of MTX response. In this work, erythroblastoid cells were exposed to MTX at the physiologic concentration of 1,000 nM and analyzed using three metabolomic platforms to give a broad spectrum of cellular metabolites. MTX pharmacological activity, defined as cellular growth inhibition, was associated with an altered cellular metabolomic profile based on the analysis of 724 identified metabolites. By discriminant analysis, MTX treatment was associated with increases in ketoisovaleric acid, fructose, galactose, and 2-deoxycytidine, and corresponding reductions in 2-deoxyuridine, phosphatidylinositol 32:0, orotic acid, and inosine monophosphate. Inclusion of data from analysis of folate metabolism in combination with chemometric and metabolic network analysis demonstrated that MTX treatment is associated with dysregulated folate metabolism and nucleotide biosynthesis, which is in line with its known mechanism of action. However, MTX treatment was also associated with alterations in a diversity of metabolites, including intermediates of amino acid, carbohydrate, and lipid metabolism. Collectively, these findings support a robust metabolic response following exposure to physiologic concentrations of MTX. They also identify various metabolic intermediates that are associated with the pharmacological activity of MTX, and are, therefore, potential molecular biomarker candidates in future preclinical and clinical studies of MTX efficacy in autoimmune arthritis.