Browse

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

ID PMID Title PublicationDate abstract
27200094 SAPHIRE: Stress and Pulmonary Hypertension in Rheumatoid Evaluation-A Prevalence Study. 2016 Pulmonary artery hypertension (PAH) is a disorder of elevated resistance in the pulmonary arterial vessels, reflected by elevation of measured pulmonary artery pressure (PAP), and presenting with breathlessness and, if untreated, progressing to right heart failure and death. The heightened prevalence of PAH in populations with underlying systemic autoimmune conditions, particularly scleroderma and its variants, is well recognised, consistent with the proposed autoimmune contribution to PAH pathogenesis, along with disordered thrombotic, inflammatory, and mitogenic factors. Rheumatoid arthritis (RA) is one of a group of systemic autoimmune conditions featuring inflammatory symmetrical erosive polyarthropathy as its hallmark. This study explored the prevalence of PAH in a population of unselected individuals with RA, using exercise echocardiography (EchoCG). The high prevalence of EchoCG-derived elevation of PAP (EDEPP) in this population (14%) suggests that, like other autoimmune conditions, RA may be a risk factor for PAH. Patients with RA may therefore represent another population for whom PAH screening with noninvasive tools such as EchoCG may be justified.
27014994 Monocyte MicroRNA Expression in Active Systemic Juvenile Idiopathic Arthritis Implicates M 2016 Sep OBJECTIVE: Systemic juvenile idiopathic arthritis (JIA) is an inflammatory disease of childhood in which cells of the monomyelocytoid lineage are thought to be key effector cells. Monocytes from patients with systemic JIA have a distinct phenotype, with features of both M1 and M2 alternative activation. MicroRNAs are critical regulators of monocyte polarization and function, but cellular microRNAs in systemic JIA have not been examined systematically. METHODS: MicroRNA TaqMan arrays were used to determine the expression profiles of monocytes from children with systemic JIA. Expression of microRNA-125a-5p (miR-125a-5p) and its contribution to monocyte polarization were examined using in vitro-polarized THP-1 cells and primary human monocytes. RESULTS: A total of 110 microRNAs were found to be differentially expressed in monocytes from patients with active systemic JIA, including molecules implicated in rheumatoid arthritis pathogenesis, cytokine production, and monocyte polarization. MicroRNA-125a-5p was identified as being highly up-regulated in monocytes from children with active systemic JIA, as compared to those from children with clinically inactive JIA or those with active polyarticular JIA, and correlated with systemic features of the disease. In vitro, monocyte miR125a-5p expression was increased after polarization under M2b or M2c conditions. Inhibition of miR-125a-5p showed that this microRNA contributed to full polarization of M2b regulatory macrophages. In contrast, miR-125a-5p overexpression enhanced M2b polarization and altered other polarized populations, including increasing the production of M2 markers. Indeed, in vitro overexpression of this microRNA altered the macrophage phenotype toward that observed in systemic JIA. CONCLUSION: Children with active systemic JIA have profound alterations in the expression of microRNAs that are implicated in monocyte function and polarization. One of these microRNAs, miR-125a-5p, is also a regulator of immunoregulatory M2b macrophages.
26321488 Deregulation of TNF expression can also cause heart valve disease. 2016 Jan High levels of the pro-inflammatory cytokine tumour necrosis factor (TNF) have been associated with many diseases including rheumatoid arthritis (RA), ankylosing spondylitis (AS), inflammatory bowel disease (IBD) and psoriasis. Although it has been clear for twenty-five years that TNF plays a major role in RA and AS, two major questions remain unanswered: (1) What mechanism underlies the loss of control of TNF levels in patients? (2) How does TNF exert its detrimental effects? Nonetheless, biological anti-TNF drugs have become the most successful treatment of these conditions with a third of patients entering remission, and the global market for biological TNF inhibitors is now estimated at around US$35 billions. However, their use is limited by their cost, the fact that they need to be injected, non-negligible side effects and the development of resistance due to the protein (thus antigenic) nature of these TNF inhibitors. It looks inevitable that new approaches to lower the amount of TNF should be considered. To do this, a better understanding of the regulation of TNF expression is necessary.
24712657 Chlamydia trachomatis elementary bodies in synovial fluid of patients with reactive arthri 2016 May OBJECTIVES: Reportedly, there is little information on the magnitude of genitourinary-induced reactive arthritis (gReA) from India. Genital infection with Chlamydia trachomatis is a major health problem in India because of its high prevalence; therefore, this study was conducted with the aim to screen ReA/undifferentiated spondyloarthropathy (uSpA) patients (n = 20) attending a major city hospital in New Delhi, for investigating the presence of intra-articular chlamydial antigen in knee joints. Patients with rheumatoid arthritis (RA) and osteoarthritis (OA) served as controls (n = 20). METHODS: Synovial fluid samples were screened for chlamydial elementary bodies (EBs) using a commercial kit (MicroTrak C. trachomatis Direct Specimen Test; Trinity Biotech, USA) for performing direct fluorescence assay (DFA). RESULTS: Chlamydia trachomatis EBs were detected in the synovial fluid cell deposits of six patients in Group I, namely, 33.3% (4/12) ReA and 25% (2/8) uSpA. All C. trachomatis positive patients exhibited an oligoarticular clinical picture with knee joint involvement. In the synovial fluid cell deposits of control patients, namely, RA/OA, no chlamydial EBs could be detected. CONCLUSIONS: This is the first study reporting the presence of C. trachomatis EBs in the synovial fluid of spondyloarthropathy patients, namely, ReA/uSpA from our country and it can be concluded that the prevalence of C. trachomatis-induced ReA is underestimated. Although our study had limitations in terms of sample size and lower sensitivity of DFA, yet this test can be used as an initial diagnostic tool for screening and patients with positive results may undergo specific tests for validation.
28040397 Should Preoperative Antibiotics Be Tailored According to Patient's Comorbidities and Susce 2017 Apr BACKGROUND: Preoperative antibiotic prophylaxis remains one of the most important strategies for preventing periprosthetic joint infection (PJI). Current guidelines recommend giving universal antibiotic prophylaxis to all total joint arthroplasty patients regardless of their medical conditions or immune status; however, no studies have evaluated the individualizing of antibiotics. The aims of this study were (1) to determine if comorbidities influence the organism profile of PJIs, and (2) to investigate if the efficacy of two different perioperative antibiotics (cefazolin or vancomycin) for preventing PJI is affected by patient's comorbidities. METHODS: Using an institutional database of 1022 PJIs, the influence of different patient's comorbidities on the organism profile was evaluated. To investigate the influence of perioperative antibiotics (cefazolin or vancomycin monotherapy) on PJI rate, 8575 primary total joint arthroplasties were identified, crossmatched for PJI, and analyzed based on the comorbidities of the cohort. The PJI rate of each antibiotic within each comorbidity was compared. RESULTS: Although no comorbidities were associated with an increased rate of Gram-positive infections or Gram-negative infections, metastatic disease (odds ratio [OR] 5.71, P = .018), congestive heart failure (OR 2.2, P = .010), chronic pulmonary disease (OR 1.76, P = .015), and diabetes mellitus (OR 1.66, P = .019) were associated with antibiotic resistant organisms. However, there was no difference in the PJI rate between cefazolin and vancomycin monotherapy when stratifying for diabetes mellitus, rheumatoid arthritis, liver disease, and hypothyroidism. CONCLUSION: The results of the present study support the current recommendations of a universal antibiotic prophylaxis protocol rather than an antibiotic regimen individualized to a patient's comorbidities.
27057353 Rituximab Downregulates Gene Expression Associated with Cell Proliferation, Survival, and 2016 Objective. To clarify molecular mechanisms for the response to rituximab in a longitudinal study. Methods. Peripheral blood from 16 RA patients treated with rituximab for a single treatment course and 26 healthy controls, blood and knee articular cartilages from 18 patients with long-standing RA, and cartilages from 14 healthy subjects were examined. Clinical response was assessed using ESR, ACPA, CRP, RF, DAS28 levels, CD19+ B-cell counts, bone erosion, and joint space narrowing scores. Protein expression in PBMCs was quantified using ELISA. Gene expression was performed with quantitative real-time PCR. Results. A decrease (p < 0.05) in DAS28, ESR, and CRP values after rituximab treatment was associated with the downregulation of MTOR, p21, caspase 3, ULK1, TNFα, IL-1β, and cathepsin K gene expression in the peripheral blood to levels found in healthy subjects. MMP-9 expression remained significantly higher compared to controls although decreased (p < 0.05) versus baseline. A negative correlation between baseline ULK1 gene expression and the number of tender joints at the end of follow-up was observed. Conclusions. The response to rituximab was associated with decreased MTOR, p21, caspase 3, ULK1, TNFα, IL-1β, and cathepsin K gene expression compared to healthy subjects. Residual increased expression in MMP-9, IFNα, and COX2 might account for remaining inflammation and pain. High baseline ULK1 gene expression indicates a good response in respect to pain.
27799933 Ectopic Lymphoid Structures: Powerhouse of Autoimmunity. 2016 Ectopic lymphoid structures (ELS) often develop at sites of inflammation in target tissues of autoimmune diseases, such as rheumatoid arthritis, Sjögren's syndrome, multiple sclerosis, myasthenia gravis, and systemic lupus erythematosus. ELS are characterized by the formation of organized T/B cells aggregates, which can acquire follicular dendritic cells network supporting an ectopic germinal center response. In this review, we shall summarize the mechanisms that regulate the formation of ELS in tertiary lymphoid organs, with particular emphasis on the role of lymphoid chemokines in both formation and maintenance of ELS, the role of emerging positive and negative regulators of ELS development and function, including T follicular helper cells and IL-27, respectively. Finally, we shall discuss the main functions of ELS in supporting the affinity maturation, clonal selection, and differentiation of autoreactive B cells contributing to the maintenance and perpetuation of humoral autoimmunity.
26996070 Arthritis-induced alveolar bone loss is associated with changes in the composition of oral 2016 Jun Rheumatoid arthritis (RA) and periodontitis (PD) are chronic inflammatory disorders that cause bone loss. PD tends to be more prevalent and severe in RA patients. Previous experimental studies demonstrated that RA triggers alveolar bone loss similarly to PD. The aim of this study was to investigate if arthritis-induced alveolar bone loss is associated with modification in the oral microbiota. Checkerboard DNA-DNA hybridization was employed to analyze forty oral bacterial species in 3 groups of C57BL/6 mice: control (n = 12; without any challenge); Y4 (n = 8; received oral inoculation of Aggregatibacter Actinomycetemcomitans strain FDC Y4) and AIA group (n = 12; chronic antigen-induced arthritis). The results showed that AIA and Y4 group exhibited similar patterns of bone loss. The AIA group exhibited higher counts of most bacterial species analyzed with predominance of Gram-negative species similarly to infection-induced PD. Prevotella nigrescens and Treponema denticola were detected only in the Y4 group whereas Campylobacter showae, Streptococcus mitis and Streptococcus oralis were only found in the AIA group. Counts of Parvimonas micra, Selenomonas Noxia and Veillonella parvula were greater in the AIA group whereas Actinomyces viscosus and Neisseira mucosa were in large proportion in Y4 group. In conclusion, AIA is associated with changes in the composition of the oral microbiota, which might account for the alveolar bone loss observed in AIA mice.
26957111 A prospective comparison of telemedicine versus in-person delivery of an interprofessional 2017 Feb Introduction We evaluated two modes of delivery of an inflammatory arthritis education program ("Prescription for Education" (RxEd)) in improving arthritis self-efficacy and other secondary outcomes. Methods We used a non-randomized, pre-post design to compare videoconferencing (R, remote using telemedicine) versus local (I, in-person) delivery of the program. Data were collected at baseline (T(1)), immediately following RxEd (T(2)), and at six months (T(3)). Self-report questionnaires served as the data collection tool. Measures included demographics, disorder-related, Arthritis Self-Efficacy Scale (SE), previous knowledge (Arthritis Community Research and Evaluation Unit (ACREU) rheumatoid arthritis knowledge questionnaire), coping efficacy, Illness Intrusiveness, and Effective Consumer Scale. Analysis included: baseline comparisons and longitudinal trends (R vs I groups); direct between-group comparisons; and Generalized Estimating Equations (GEE) analysis. Results A total of 123 persons attended the program (I: n = 36; R: n = 87) and 111 completed the baseline questionnaire (T(1)), with follow-up completed by 95% ( n = 117) at T(2) and 62% ( n = 76) at T(3). No significant baseline differences were found across patient characteristics and outcome measures. Both groups (R and I) showed immediate effect (improved arthritis SE, mean change (95% confidence interval (CI)): R 1.07 (0.67, 1.48); I 1.48 (0.74, 2.23)) after the program that diminished over six months (mean change (95% CI): R 0.45 (-0.1, 0.1); I 0.73 (-0.25, 1.7)). For each of the secondary outcomes, both groups showed similar trends for improvement (mean change scores (95% CI)) over time. GEE analysis did not show any meaningful differences between groups (R vs I) over time. Discussion Improvements in arthritis self-efficacy and secondary outcomes displayed similar trends for I and R participant groups.
25182154 Inhibition mechanism of Qingluo Tongbi Granule () on osteoclast differentiation induced by 2015 Apr OBJECTIVE: To study the mechanism underlying the inhibitory effect of Qingluo Tongbi Granule (, QTG) on osteoclast differentiation in rheumatoid arthritis in rats. METHODS: Fibroblast and monocyte co-culture were used to induce osteoclast differentiation in adjuvant-induced arthritic (AIA) rats. Serum containing QTG was prepared and added to the osteoclasts, and activation of the tumor necrosis factor receptor-associated factor 6/mitogen-activated protein kinase/nuclear factor of activated T cells, cytoplasmic1 (TRAF6/MAPK/NFATc1) pathways was examined. RESULTS: The induced osteoclasts were multinucleated and stained positive for tartrate-resistant acid phosphatase (TRAP) staining. Serum containing QTG at 14.4, 7.2 or 3.6 g/kg inhibited the activation of TRAF6, extracellular regulated protein kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 and decreased the percentage of cells with nuclear NFATc1 in a dose-dependent manner, the high and middle doses exhibited clear inhibitory activity (P<0.01 and P<0.05, respectively). After the addition of MAPK inhibitors, the NFATc1 expression showed no significant difference compared with the control group (P>0.05). CONCLUSIONS: Serum containing QTG could generally inhibit the TRAF6/MAPK pathways and possibly inhibit the NFATc1 pathway. In addition, QTG may regulate other signaling pathways that are related to osteoclast differentiation and maturation.
27729929 Assessment of collagen antibody-induced arthritis in BALB/c mice using bioimaging analysis 2016 Sep The aim of this study was to examine the therapeutic potential of sulfasalazine and prednisolone in a mouse collagen antibody-induced arthritis (CAIA) model. Twenty-five male BALB/c mice were randomly divided into five groups: group 1 (G1): control, group 2 (G2): probe control, group 3 (G3): CAIA, group 4 (G4): CAIA+sulfasalazine (10 mg/kg, oral), and group 5 (G5): CAIA+prednisolone (100 mg/kg, oral). Fluorescence bioimaging was performed in vivo 24 and 48 h after treatment with a fluorescence probe (OsteoSense® 680 EX), and all mice were sacrificed. The hind knee joints were fixed in 10% neutral phosphate-buffered formalin, and micro-computed tomography (micro-CT) and histopathological analyses were performed. The paw thickness increased in a time-dependent manner in G3 mice, but trended toward a decrease in both G4 and G5 mice. Fluorescence intensity increased in G3 mice at 24 and 48 h after fluorescence probe treatment, but the fluorescence intensity in G4 and G5 mice was lower than that in G3. Micro-CT analyses showed that the joint surfaces of G3 mice had a rough and irregular articular appearance, but the occurrence of these irregularities was lower in G4 and G5. Hematoxylin and eosin and Safranin O-fast green staining confirmed that destruction of the cartilage and bony structures, synovial hyperplasia, and inflammatory cell infiltration all occurred in G3, and that the occurrence of these phenomena was lower in G4 and G5 than in G3. Taken together, these results suggest that sulfasalazine and prednisolone can reduce acute rheumatoid arthritis in mice.
25000588 Discovery of selective and orally bioavailable protein kinase Cθ (PKCθ) inhibitors from 2015 Jan 8 Protein kinase Cθ (PKCθ) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKCθ inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.
24718489 Vitamin D status of patients with early inflammatory arthritis. 2015 Feb The present study aimed to investigate the vitamin D status in patients with early inflammatory arthritis (EIA). We conducted a retrospective study among patients who presented with EIA at the outpatient rheumatology clinic of a tertiary referral center between March 2012 and February 2013. In total, 101 subjects with EIA (≥1 swollen joint and symptom duration of ≤6 months, not explained by another disease) and 101 healthy controls matched for age, sex, and the month of serum vitamin D measurements were enrolled. Serum 25-hydroxy vitamin D (25-OHD) concentrations were assessed by radioimmunoassay. Vitamin D "deficiency" and "severe deficiency" were defined as serum 25-OHD levels <20 and <10 ng/mL, respectively. Among EIA patients, rheumatoid arthritis (RA) was classified according to the 2010 American College of Rheumatology/European League against Rheumatism criteria. Vitamin D deficiency was highly prevalent among EIA patients, but no significant differences in the frequency of vitamin D deficiency of EIA patients and controls were observed (75.2 vs 65.3%, p = 0.106). Additionally, in spring and summer, EIA patients had significantly lower serum 25-OHD concentrations than controls, but the opposite trend was observed in autumn. Among 101 EIA patients, 38 (37.1%) were classified as having RA. Severe vitamin D deficiency in EIA patients was significantly associated with the higher likelihood of being classified as having RA. In conclusion, the frequency of vitamin D deficiency in EIA patients was comparable to that in controls, but severe vitamin D deficiency was associated with the presence of RA among EIA patients.
26490030 Cytomegalovirus as an Insidious Pathogen Causing Duodenitis. 2015 A 60-year-old woman with rheumatoid arthritis treated with methotrexate for a decade complained of slight epigastric discomfort. A positive cytomegalovirus (CMV) antigenemia test indicated the probability of CMV-related gastrointestinal infection, for which esophagogastroduodenoscopy was performed. Endoscopic findings showed a non-specific duodenal mucosal lesion;however, pathological investigation revealed evidence of CMV duodenitis. There is scarce information on the clinical and pathological features of CMV-related duodenitis, likely due to its low prevalence. CMV infection in the upper gastrointestinal tract should be considered as a differential diagnosis in high-risk individuals, particularly those with symptoms relating to the digestive system. Biopsy examinations are preferable for the definitive diagnosis of CMV gastrointestinal infection, even without specific endoscopic features.
26485907 [Zheng Classification in Chinese Medicine: from Its Integration with Disease Diagnosis to 2015 Aug As the core of traditional Chinese medicine theory, Zheng (syndrome, or pattern) classification will promote personalized medicine by changing the clinical diagnosis into a more precise mode when integrating Zheng classification with disease diagnosis approaches. The author adopted rheumatoid arthritis (RA) as a disease model, to explore the scientific fundamentals of Zheng classification based on disease diagnosis using systemic biological approaches and evidence-based medicine design, as well as developed novel approaches on the methodology of clinical effectiveness evaluation on Chinese medicine and R&D of combinational drugs design based on Fu Fang (Chinese herbal formula). Some unique research design and methods are herein introduced.
26369826 Advances in the Development of Class I Phosphoinositide 3-Kinase (PI3K) Inhibitors. 2016 The PI3K signaling cascade is the key moderator of cell proliferation, survival, motility, and apoptosis. Class I PI3K proteins are well characterized and linked to thrombosis (PI3Kβ), rheumatoid arthritis (PI3Kδ), and cancer (PI3Kα). In this review, we explore the latest progress in the design and development of selective Class I PI3K inhibitors from the perspective of drug design and structure activity relationships.
26065006 Bone Loss Triggered by the Cytokine Network in Inflammatory Autoimmune Diseases. 2015 Bone remodeling is a lifelong process in vertebrates that relies on the correct balance between bone resorption by osteoclasts and bone formation by osteoblasts. Bone loss and fracture risk are implicated in inflammatory autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and systemic lupus erythematosus. The network of inflammatory cytokines produced during chronic inflammation induces an uncoupling of bone formation and resorption, resulting in significant bone loss in patients with inflammatory autoimmune diseases. Here, we review and discuss the involvement of the inflammatory cytokine network in the pathophysiological aspects and the therapeutic advances in inflammatory autoimmune diseases.
25827514 Macro-creatine kinase: a neglected cause of elevated creatine kinase. 2015 Apr Macro-creatine kinase (macro-CK) is a neglected cause of raised CK. Over a 10-year period, we observed five cases. Three patients had macro-CK type 1. One patient with fibromyalgia underwent several explorations to find a muscular pathology; another, who had elevated CK-MB (muscle-brain fraction) activity, was referred to a cardiologist, and statin therapy was erroneously discontinued in two patients. Two patients had macro-CK type 2: a man with a neuroendocrine carcinoma and a woman with rheumatoid arthritis. Diagnosis of type 1 obviates the need to carry out pointless and expensive investigations seeking a neuromuscular or cardiac pathology, and also, the unwarranted discontinuation of statin therapy. Type 2 must prompt investigations for a neoplasm.
25652649 Th17 cells in autoimmune diseases. 2015 Mar Th17 cells are a new subset of CD4(+) T cells involved in the clearance of extracellular pathogens and fungi. Accumulating evidence suggests that Th17 cells and their signature cytokines have a pivotal role in the pathogenesis of multiple autoimmune-mediated inflammatory diseases. Here, we summarize recent research progress on Th17 function in the development and pathogenesis of autoimmune diseases. We also propose to identify new small molecule compounds to manipulate Th17 function for potential therapeutic application to treat human autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, inflammatory bowel disease, and multiple sclerosis.
27407251 The role of physiological elements in future therapies of rheumatoid arthritis. III. The r 2015 Each material consisting of charged particles can be influenced by a magnetic field. Polarized particles play an essential role in almost all physiological processes. Locally generated electromagnetic fields several physiological processes within the human body, for example: stimulation of nerves, muscles, and cardiac electrical activity. This phenomenon is used today in many medical applications. In this article, we discuss ways in which electromagnetic field affects the physiological and pathological processes in cells and tissues. This knowledge will help to better understand the electrophysiological phenomenon in connective tissue diseases and can bring new therapeutic strategies (in the form of "invisible drugs") for the treatment of rheumatic diseases?