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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
30237627 Comorbidities in rheumatic arthritis. 2018 OBJECTIVES: Rheumatoid arthritis (RA) is one of the most common systemic inflammatory diseases, but its etiology is still not fully known. The aim of this preliminary study was to assess what particular comorbidities are involved in the progression of RA and determine the influence that the aforementioned diseases have on each other. MATERIAL AND METHODS: Forty patients with diagnosed RA according to EULAR/ACR criteria from 2010 were included in the study. The majority of the group was female (n = 35; 87.5%). Patients were tested using routine laboratory and imaging methods allowing diagnosis and assessment of disease activity. Dual energy X-ray absorptiometry was also evaluated for mineral density. The activity of the disease was assessed using the disease activity score DAS28 (ESR) and SDAI (Simplified Disease Activity Index). RESULTS: Among studied patients, based on the DAS28 index, 9 patients were in the remission phase (22.5%) and 12 (30%) had high disease activity. Increased values of CRP were observed in the majority of patients (65%). The group analysis demonstrated the most common comorbidities in patients with RA, as follows: hypertension (n = 14; 35%) and osteoporosis or osteopenia (n = 13; 32.6%). CONCLUSIONS: Patients with rheumatoid arthritis (RA) are more susceptible to developing hypertension and osteoporosis. We did not observe a significant association between other comorbidities and activity of RA. The next study will assess a larger number of patients.
29804149 Advances in the diagnosis and treatment of Sjogren's syndrome. 2018 Jul Sjogren's syndrome (SS) is a systemic autoimmune disease that primarily affects the exocrine glands, resulting in dryness of the eyes and mouth due to lymphocytic infiltration of the salivary and lacrimal glands along with arthritis, kidney, liver, and lung involvement, chronic fatigue, musculoskeletal pain, vasculitis, and so on. Considerable advance has been made for the classification and treatment of primary SS in the past few years. This article reviews the recent classification criteria for primary SS and briefly discusses the conventional and novel therapies of the disease.
29204673 The Role of Autoantibodies in Bone Metabolism and Bone Loss. 2018 May Many autoimmune diseases are associated with deranged bone metabolism. The resulting localized or systemic bone loss can compromise the quality of life of patients by causing local bone deformities or fragility fractures. There is emerging evidence that antibodies have a direct impact on key players of bone homeostasis, in particular osteoclasts. Clinical and pre-clinical studies provide insight into the function of autoantibodies related to Rheumatoid Arthritis (rheumatoid factor, anti-citrullinated protein antibodies, and anti-carbamylated protein antibodies) and their inflammation-independent interaction with bone cells. Furthermore, we summarize the current knowledge about neutralizing antibodies to the antiresorptive protein osteoprotegerin, which have been described in patients with Coeliac Disease, Rheumatoid Arthritis, and Spondyloarthritis.
30598469 Rheumatoid meningitis: successful remission with rituximab. 2018 Dec 31 A 53-year-old male with rheumatoid arthritis presented with recurrent headaches, seizures and right-sided lower extremity paralysis while on antiepileptic medications. Work up revealed pachymeningeal and leptomeningeal enhancement on brain MRI. Differential diagnosis included a variety of infections, neoplasm and vasculitis. Histopathology showed findings consistent with rheumatoid meningitis (RM). Ultimately based on symptoms, MRI findings and tissue pathology, he was diagnosed with RM. Intravenous pulse dose steroids were initiated followed by rituximab every 6 months, resulting in significant improvement of the brain MRI findings. Patient has remained seizure free.
31428318 Content analysis of Twitter in relation to biological treatments for chronic inflammatory 2019 May OBJECTIVE: To analyse the volume and content of tweets in relation to biological treatments for chronic inflammatory arthropathies. METHODS: A Twitter analysis was carried out during one month using the following keywords: 'rheumatoid arthritis', 'ankylosing spondylitis', 'psoriatic arthritis' and their biological therapies: 'abatacept', 'adalimumab', 'certolizumab', 'etanercept', 'golimumab', 'infliximab' and 'tocilizumab'. Tweets were hand-coded and filtered for content. RESULTS: 25 441 tweets contained at least one of the keywords. After filtering, 2480 tweets were included in the analysis. Regarding the 983 tweets about therapies, the most frequently mentioned biologics were 'adalimumab' (n=359), 'infliximab' (n= 278) and 'etanercept' (n= 205). In the 1497 tweets about diseases, the term 'rheumatoid arthritis' (n= 1109) was used more frequently than 'psoriatic arthritis' (n= 233) and 'ankylosing spondylitis' (n= 155). The most commonly addressed subjects in the tweets in relation to biological therapies were related to safety/adverse events (136 of 983 (13.8%)) and to administration, particularly drug infusion (60 of 983 (6.1%)) and self-administration (57 of 983 (5.8%)). Regarding diseases, the most commonly addressed subjects were non-pharmacological recommendations such as alternative therapies (145 of 1497 (9.7%)), nutrition (128 of 1497 (8.5%)) and exercise (91 of 1497 (6.1%)). CONCLUSIONS: Twitter is widely used to search for information about biological treatments for chronic athropathies. Learning more about the subjects dealt with in the tweets will enable us to improve our understanding of the areas of greater interest and concern among patients. This could help hospital pharmacists establish patient-focused strategies addressing the needs of the patients.
30233684 Expression levels of IL-15 and IL-17 in synovial fluid of rheumatoid arthritis animal mode 2018 Oct The aim of the present study was to investigate the expression levels of interleukin-15 (IL-15) and interleukin-17 (IL-17) in synovial fluid of rheumatoid arthritis (RA) animal model, and to investigate their correlations with RA. A total of 100 Wistar rats were selected, among which 60 rats were used to establish the collagen II-induced arthritis (CIA) model as the model observation group, and the remaining 40 rats were used as blank control group. The levels of IL-15 and IL-17 in synovial fluid were detected via enzyme-linked immunosorbent assay (ELISA) at 1, 7, 14, 21 and 28 days after successful modeling. RA was evaluated by using arthritis index (AI) and pedal swelling volume. The expression levels of IL-15 and IL-17 in synovial fluid of rats in model observation group were higher than those in blank control group (P<0.05), and the levels of IL-15 and IL-17 in model observation group were gradually increased over time. In model observation group at 7 days after modeling, AI and pedal swelling volume began to be increased gradually reaching a peak at 28 days. The pedal swelling volume of CIA model rats was significantly higher than that of the blank control group (P<0.05). The increased expression levels of IL-15 and IL-17 in synovial fluid of rats in the CIA model observation group are correlated with the activity of disease, which can be used as reference indexes for the activity of RA.
29632752 Celiac Disease and Concomitant Conditions: A Case-based Review. 2018 Feb 2 Celiac disease is a chronic autoimmune disease with genetic predisposition, triggered by the ingestion of gluten. It has a wide range of clinical manifestations ranging from asymptomatic forms to classic presentation of malabsorption with diarrhea and abdominal cramps. Celiac disease can also present with several other concomitant disorders (at the time of diagnosis or during the course of celiac disease) such as: type 1 diabetes, inflammatory bowel disease, rheumatoid arthritis, thyroid disorders, nutritional deficiencies, and gram-negative sepsis. We present a 57-year-old female with past medical history of rheumatoid arthritis, who presented to the emergency department with a complaint of chronic diarrhea, complicated by gram-negative sepsis. The family history of the patient was significant for celiac disease, type 1 diabetes, and rheumatoid arthritis. The patient was closely monitored and treated appropriately. In this case-based review, we explore different associated conditions of celiac disease in the literature, as well as the patient's risk of developing malignancy.
29849661 Pseudochylothorax Combined with Spontaneous Pneumothorax: Case Report of a Rare Complicati 2018 Pleural involvement is the most frequent thoracic complication of rheumatoid arthritis (RA), usually occurring in patients with known RA. Typical rheumatoid pleural effusion is an exudate characterized by low pH and glucose levels and high LDH activity. Rarely, it has features of pseudochylothorax. Other uncommon complications are pneumothorax, hydropneumothorax, empyema, and bronchopleural fistula. The case of a 51-year-old man with a spontaneous, small, and asymptomatic hydropneumothorax with features of pseudochylothorax is presented. After careful clinical and laboratory evaluation, he was diagnosed with rheumatoid arthritis, and we admitted that the pleural changes were secondary to the connective tissue disease. He started immunosuppressive treatment and maintained stability during follow-up, without need of specific pleural treatment. We hypothesized that the pleural nodule found on the chest computed tomography scan was related with the simultaneous occurrence of pleural effusion and pneumothorax. This is a rare presentation and complication of RA, highlighting the utility of a comprehensive clinical and laboratory evaluation and focusing on the importance of pleural rheumatoid nodules in the pathogenesis of RA pleural disease.
30116727 Survivin Measurement improves Clinical Prediction of Transition From Arthralgia to RA-Biom 2018 Background: Arthralgia often predates development of rheumatoid arthritis (RA). A set of joint symptoms commonly found in patients during their transition from arthralgia to RA, has been recently proposed. Aim: To combine clinical and serological markers and to improve recognition of imminent rheumatoid arthritis (RA) among patients with arthralgia. Methods: The total of 1,743 first-visit patients attending the rheumatology ward in Gothenburg for joint symptoms were identified during 12 consecutive months. Among those, 63 patients were classified as RA, 73 had undifferentiated arthritis and 180 had unexplained arthralgia. New RA cases, which prospectively developed during 48 months, comprised the preclinical (pre) RA group. The joint symptoms of the first-visit were analyzed aiming to distinguish patients with arthralgia and arthritis, and patients with pre-RA, who later developed the disease. The receiver operating characteristics curves were constructed. In the model, symptoms with the odds ratio >2.0 between the arthralgia and pre-RA were combined with information about RA-specific antibodies, C-reactive protein (CRP), and survivin in serum. Results: The proposed set of clinical symptoms distinguished the arthralgia patients from RA and pre-RA. Presence of survivin in serum showed strong association with clinical joint symptoms in arthralgia. A combination of symptoms in several small joint areas, increasing number of joints with symptoms, and patient's experience of swelling in small hand joints at the first visit identified pre-RA cases with 93% specificity. Grouping those symptoms with information about survivin, RA-specific antibodies, and CRP (or gender) in the final algorithm achieved 91% specificity and 55.2% of positive prediction for transition from arthralgia to RA. Conclusion: Clinical and serological parameters in combination aid recognition of imminent RA among arthralgia patients with appropriate sensitivity.
29761402 Cytokine-Induced Acute Inflammatory Monoarticular Arthritis. 2018 Animal models of arthritis enable us to investigate the pathogenesis of the disease and also to evaluate new therapies. Here we describe two different acute inflammatory monoarticular arthritis models (mBSA/IL1β and mBSA/GM-CSF) providing a more rapid and potentially simplified approach to investigate the pathogenesis.
29922080 Factors correlated with the improvement of endothelial dysfunction during Abatacept therap 2018 BACKGROUND: Rheumatoid arthritis patients are exposed to a high risk of cardiovascular morbidity and mortality even in the early phases of the disease. METHODS: We evaluated carotid common carotid intimal media thickness (ccIMT) intimal thickness and brachial flow-mediated dilation (FMD) of 45 rheumatoid arthritis patients without known cardiovascular risk factors or heart disease on a stable dose of prednisone 5.2±1.2 mg/day and Methotrexate 11.5±2.1 mg at baseline (T0) and after 12 months (T1) of treatment with Abatacept 125 mg/week. The comparison between T0 and T1 (t- and Mann-Whitney test), correlation (Spearman r), and predictivity (linear regression) of FMD, ccIMT vs clinical and laboratory parameters (disease activity 28 score, tumor necrosis factor alpha [TNFα], interleukin-6, erythrocyte sedimentation rate, C-reactive protein (CRP), CD3+, CD3+/CD4+, CD3+/CD8+, CD19+(B), CD20+(B), NK CD3-CD56+CD16+, CD14+ HLA DR+, CD4+CD28+, CD4+CD28, rheumatoid factor IgM, IgA, RF IgG, anti-citrullinated peptide antibodies) were also evaluated. RESULTS: During Abatacept treatment, ccIMT and FMD remained stable and disease activity 28 score, CRP, erythrocyte sedimentation rate, and interleukin-6 decreased significantly (p=0.0001, 0.002, 0.0002, 0.0001 respectively). At T0, only ccIMT resulted as correlated with baseline TNFα values (p=0.0245) in an inverse proportion. At T1, ccIMT correlated with CD3/CD8+ lymphocytes number (p=0.0351) and FMD with CRP (p=0.0075). In regression analysis, baseline ccIMT and FMD had a low predictivity for TNFα (p=0.011) and CRP (p=0.049) at T1, respectively. CONCLUSION: This study shows that the endothelial function remained stable during Abatacept treatment.
30345838 DNA hypermethylation of SFRP2 influences the pathology of rheumatoid arthritis through the 2018 Oct 20 In this work, the expression of secreted frizzled related protein 2 (SFRP2) in rheumatoid arthritis (RA) model rats and the mechanisms of SFRP2 on the RA pathogenesis were investigated. Data suggested that SFRP2 was significantly down-regulated in RA model rats compared with normal control, and overexpression of SFRP2 suppressed the RA pathogenesis and the canonical Wnt signaling in fibroblast-like synovial cells (FLS) from RA model rats, whereas knockdown of SFRP2 got an opposite observation. Interestingly, 5-azadC treatment up-regulated the SFRP2 expression, inhibited the FLS proliferation, suppressed the expression of IL-6 and IL-8 and the fibronectin production, suggesting that the decreased SFRP2 in RA model rats was due to the DNA methylation. Furthermore, DNMT1 knockdown up-regulated the SFRP2 expression, DNMT1 overexpression inhibited the SFRP2, and the quantitative methylation-specific PCR (qMSP) confirmed that the DNMT1 has direct methylation roles for the SFRP2 promoter, leading to a regulation of FLS proliferation and fibronectin expression in RA model rats. In addition, up-regulated MeCP2 was involved in the SFRP2 regulation and the pathogenesis of RA model rats, and MeCP2 and DNMT1 have synergistic inhibition roles in the SFRP2 expression. Combination of DNMT1 and DNA methylation may be a promising treatment strategy for individuals with RA in which SFRP2 is down-regulated.
30186380 HOXD10 silencing suppresses human fibroblast-like synoviocyte migration in rheumatoid arth 2018 Sep Homeobox D10 (HOXD10) belongs to the human homeobox (HOX) gene family, and the homologous protein encoded by HOX primarily controls cell differentiation and morphogenesis during embryonic development. The current study aimed to explore the roles and mechanisms of HOXD10 in the migration of human fibroblast-like synoviocytes in rheumatoid arthritis (RAFLS). Cell counting kit-8, cell migration and wound healing assays were performed to examine the cell viability and migration, respectively. Western blot and reverse transcription-quantitative polymerase chain reaction assays were used to evaluate the association between mRNA and protein expression levels. The results revealed HOXD10 expression was upregulated in tissues from patients with RA. HOXD10 silencing inhibited the viability of RAFLS. In addition, HOXD10 silencing suppressed the migration of RAFLS through modulating the expression of cadherin-11, N-cadherin, E-cadherin, vimentin, zonula occludens-1, integrinβ1 and paxillin. In conclusion, HOXD10 silencing downregulates the p38/c-Jun N-terminal kinase signaling pathway, which in turn may suppress the migration of RAFLS.
30325625 2018 Mar The objective of this review is to assess the benefits and harms of drugs used in adult patients with moderate to severe rheumatoid arthritis (RA) in whom treatment with methotrexate (MTX) has failed or who are intolerant to MTX.
30367550 Betulinic acid inhibits cell proliferation, migration, and inflammatory response in rheuma 2018 Oct 26 Betulinic acid (BA), a pentacyclic triterpene derived from the bark of the white birch tree, has been reported to have a variety of pharmacological effects, including antioxidant, anti-inflammatory, antitumor, immunomodulatory, and antiarthritis properties. However, the role of BA in rheumatoid arthritis (RA) remains unclear. Thus, the objective of this study was to examine the effects of BA on RA fibroblast-like synoviocytes (RA-FLS) proliferation, migration, and inflammatory response, and further explore the potential underlying mechanisms. Our results showed that BA inhibited the proliferation, migration, and invasion of RA-FLSs. BA also attenuated tumor necrosis factor-α (TNF-α), enhanced matrix metalloproteinases (MMPs) expression, and inflammatory cytokines production in RA-FLS. Furthermore, BA prevented the activation of Akt/NF-κB pathway in RA-FLS exposed to TNF-α. In conclusion, these findings indicated that BA inhibits cell proliferation, migration, and inflammatory response in RA-FLS; and the Akt/NF-κB signaling pathway was involved in the protective effect of BA on RA-FLS. Thus, BA might be a potential therapeutic agent for the treatment of RA.
30294292 Spousal Support for Patients With Rheumatoid Arthritis: Getting the Wrong Kind Is a Pain. 2018 Research indicates that perceived support availability is beneficial, with support available from the spouse particularly important for well-being. However, actual support mobilization has shown mixed associations with recipient well-being. The primary goal of the present study was to go beyond examining the effects of global perceptions of support on recipient outcomes. Instead, we examined the effects of several specific types of support that have been found to be important in the clinical literature. In this study, we followed both members of couples in which one partner was diagnosed with rheumatoid arthritis. Patients provided reports on pain for both mornings and evenings across 1 week. Both partners also reported esteem, solicitous, and negative support mobilization received by the patient. We found that patient pain tended to increase across the day following increases in patient reports of negative support receipt and partner reports of solicitous support provision. We also found that patient pain tended to decrease across the day when partners reported increased levels of esteem support provision. Reverse causation analyses indicated higher levels of patient pain may lead partners to increase solicitous support mobilization to the patient. Findings underscore the importance of examining both partners' reports of support within a dyadic coping framework. They further suggest that not all forms of support are equally beneficial, calling for a finer grained assessment of specific support transactions.
29470833 Cost of Depression in Japanese Patients with Rheumatoid Arthritis: Evidence from Administr 2018 Jun INTRODUCTION: To determine the cost of depression comorbidity among Japanese adults with rheumatoid arthritis (RA). METHODS: A retrospective database study of 8968 patients diagnosed with RA between 2010 and 2015 and treated with any RA medication was conducted. Health care utilization characteristics were compared between patients with and without a comorbidity of depression. Propensity score matching was applied to ensure a balanced comparison between the two cohorts. RESULTS: The prevalence of a depression comorbidity was found for 5% of the total RA patients. This comorbidity was associated with 62% (56%) higher total outpatient visits and 66% (163%) higher rate of emergency room visits after 6 (12) months. CONCLUSIONS: Burden of depression among RA patients in Japan is relatively high and awareness for depression as a comorbidity of RA needs to be reinforced. FUNDING: Janssen Pharmaceutical KK.
30213779 Using a ResearchKit Smartphone App to Collect Rheumatoid Arthritis Symptoms From Real-Worl 2018 Sep 13 BACKGROUND: Using smartphones to enroll, obtain consent, and gather self-reported data from patients has the potential to enhance our understanding of disease burden and quantify physiological impact in the real world. It may also be possible to harness integral smartphone sensors to facilitate remote collection of clinically relevant data. OBJECTIVE: We conducted the Patient Rheumatoid Arthritis Data From the Real World (PARADE) observational study using a customized ResearchKit app with a bring-your-own-device approach. Our objective was to assess the feasibility of using an entirely digital approach (social media and smartphone app) to conduct a real-world observational study of patients with rheumatoid arthritis. METHODS: We conducted this observational study using a customized ResearchKit app with a bring-your-own-device approach. To recruit patients, the PARADE app, designed to guide patients through a series of tasks, was publicized via social media platforms and made available for patients in the United States to download from the Apple App Store. We collected patient-reported data, such as medical history, rheumatoid arthritis-related medications (past and present), and a range of patient-reported outcome measures. We included in the assessment a joint-pain map and a novel objective assessment of wrist range of movement, measured by the smartphone-embedded gyroscope and accelerometer. RESULTS: Within 1 month of recruitment via social media campaigns, 399 participants self-enrolled, self-consented, and provided complete demographic data. Joint pain was the most frequently reported rheumatoid arthritis symptom to bother study participants (344/393, 87.5%). Severe patient-reported wrist pain appeared to be inversely linked with the range of wrist movement measured objectively by the app. At study entry, 292 of 399 participants (73.2%) indicated a preference for participating in a mobile app-based study. The number of participants in the study declined to 45 of 399 (11.3%) at week 12. CONCLUSIONS: Despite the declining number of participants over time, the combination of social media and smartphone app with sensor integration was a feasible and cost-effective approach for the collection of patient-reported data in rheumatoid arthritis. Integral sensors within smartphones can be harnessed to provide novel end points, and the novel wrist range of movement test warrants further clinical validation.
30123796 The Utility and Limitations of CRP, ESR and DAS28-CRP in Appraising Disease Activity in Rh 2018 Introduction: Identifying and quantifying inflammatory disease activity in rheumatoid arthritis remains a challenge. Many studies have suggested that a large proportion of patients may have active inflammation, but normal inflammatory markers. Although various disease activity scores have been validated, most rely to a large degree on biomarkers such as CRP and ESR. In this study, we examine the utility and limitations of these biomarkers, as well as the DAS28-CRP in appraising disease activity in RA. Methods: Two hundred and twenty three consecutive rheumatoid arthritis reporting knee arthralgia underwent synovial sampling of the affected knee via needle arthroscopy. The synovium was examined by microscopy with H+E staining as well as immunohistochemistry, and related to the ESR, CRP and DAS28-CRP on blood samples taken immediately before arthroscopy. Results: Although a statistically significant positive correlation was observed between CRP and the level of inflammation in the biopsy retrieved (n = 197, rho = 0.43, CI 0.30-0.54, p < 0.0001), there was histological evidence of inflammation in the synovium in 49.4% of the patients who had a normal CRP. A positive correlation was also observed between ESR and the level of inflammation in the biopsy retrieved (n = 188, rho = 0.29, CI 0.15-0.42 p < 0.0001). A statistically significant but weak positive correlation was observed between the DAS28-CRP and synovial inflammation (n = 189, rho = 0.23, CI 0.09-0.37, p = 0.0011). Only the CD19 infiltrate in the synovium correlated with serum CRP (n = 70, rho = 0.32, CI 0.08-0.52, p = 0.0068). Conclusion: CRP has a moderately strong relationship with disease activity, but there are significant pitfalls in the use of this biomarker in RA, and therefore a need interpret CRP results judiciously. The results of this study underline the heterogeneity of RA, and the need to develop improved panels of biomarkers, to better stratify RA, and to identify the cohort for whom inflammatory activity cannot be measured accurately with CRP.
29423005 Transcription factor Phf19 positively regulates germinal center reactions that underlies i 2018 The Polycomb Repressive Complex 2 (PRC2) component PHD Finger Protein 19 (phf19) gene has been identified to be associated with rheumatoid arthritis (RA) risk. Here we show that Phf19 is highly expressed in murine germinal centers (GCs) and RA patients. To investigate the function of Phf19 in lymphocytes, we generated RAG1-deficient mice reconstituted with Phf19 or control-vector transduced bone marrow (BM) cells. Lymphogenesis in primary lymphoid tissues of Phf19-RM is normal, however, Phf19-RM form enlarged GCs and generate more antibody-secreting cells (ASCs). Overexpression of Phf19 promotes proliferation and survival of GC B cells and Tfh cells in vivo. The uncovered Phf19-dependent targets include the genes encoding cyclin D2, the prosurvival factor Bcl-xL and CD40-CD40 ligand axis, their regulation by Phf19 could partially elucidate the advantages observed in Phf19-overexpressing GCs. Our results underscore an unrecognized but critical function for Phf19 in GCs formation and antibody generation, and implicate the potential role of Phf19 in RA pathogenesis.