Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
---|---|---|---|---|
26092613 | Effects of rheumatoid arthritis on household chores and leisure-time activities. | 2015 Nov | The aim of the study was to determine household chores and leisure-time activities most affected by rheumatoid arthritis (RA) and to evaluate the perceived impact on performing these activities. Also, our aim was to estimate the required and received assistance for household chores. In an interview study via telephone, 124 patients with moderate-to-severe RA, visiting a tertiary-level dermatological clinic, listed spontaneously without predefined list the household chores and leisure-time activities that they considered were particularly affected by the RA. Ability to perform household chores and leisure-time activities were asked. The need for outside assistance with household chores and help received were also determined. Rheumatoid arthritis affected wide range of everyday household activities, with tasks related to cleaning of the house mentioned most often. Eleven of the categories out of 16 were similar to those included in the HAQ index. The majority of the patients (84.6 %) reported disadvantage in performing household chores because of RA. More than half of the patients (55.7 %) received assistance with household chores, women significantly more often than men (69.0 vs. 26.3 %, p < 0.01). Most of the household chores mentioned were physically demanding. Leisure-time activities listed by respondents as affected by RA were mostly related to sport. The majority of patients (77.2 %) had either reduced or completely given up at least one leisure-time activity. When estimating the total burden of the disease, the impact on both household chores and leisure-time activities should be taken into account. | |
26764956 | The onset of lipid peroxidation in rheumatoid arthritis: consequences and monitoring. | 2016 | Several epidemiological studies propose the association of rheumatoid arthritis (RA) with oxidative stress. The aim of this study was to estimate the possible onset of systemic lipid peroxidation in RA patients and its relevance for pathophysiology and monitoring of RA. Seventy-three patients with RA and 73 healthy subjects were included in the study. Lipid peroxidation was estimated by the measurement of 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal, malondialdehyde, acrolein, crotonaldehyde, 4-oxononenal, and isoprostanes (8-isoPGF(2α)) levels. Cytosolic phospholipase A(2) (cPLA(2)), platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (GSH-Px) activities and vitamin E levels were also determined. In parallel, the plasma levels of phospholipid arachidonic acid (AA), linoleic acid (LA), and 4-HNE-protein adducts were monitored. Plasma of RA patients had increased vitamin E levels, but decreased GSH-Px activity and phospholipid AA and LA levels when compared to levels of the healthy subjects. The levels of aldehydes were significantly increased in the plasma of the RA patients and even more in urine. Significant increases in HNE-modified protein adducts was observed for the first time in plasma of RA patients, while the activities of PAF-AH and cPLA(2) were decreased. The 8-isoPGF(2α) levels were 9-fold higher in plasma and 3-fold higher in urine of RA patients and were related to the severity of disease. The levels of lipid peroxidation products in plasma and in urine suggest the relationship between lipid peroxidation and the development of RA. Additionally, urine 8-isoPGF(2α), plasma 4-HNE and 4-HNE-protein adducts appear to be convenient biomarkers to monitor progression of this autoimmune disease. | |
26746625 | FCRL3 gene polymorphisms as risk factors for rheumatoid arthritis. | 2016 Feb | BACKGROUND: Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. As a member of FCRLs clusters, Fc receptor-like 3 (FCRL3) has been recognized as a neoteric autoimmune activation factor for RA. The aim of our study is to evaluate the correlation between four single-nucleotide polymorphisms (SNPs) on FCRL3 and RA risk in a Chinese Han population. MATERIAL AND METHODS: The hospital-based case-control study included 630 RA patients together with 696 healthy individuals as the control group and all subjects are Chinese ancestry. Four tagging single-nucleotide polymorphisms (tag-SNPs) on FCRL3 were selected and genotyped by TaqMan assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were employed to evaluate the correlations between FCRL3 polymorphisms and RA. A systematic meta-analysis was also carried out based on the present study and previously published studies to further examine the association between FCRL3 variations and RA risk. RESULTS: Significant association was found between -169T/C SNP and RA risk (CC vs. TT, OR=1.62, 95% CI=1.18-2.22; TC/CC vs. TT, OR=1.47, 95% CI=1.18-1.84; C vs. T, OR=1.32, 95% CI=1.12-1.54). Apart from that, mutations of -169T/C was significantly correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) positive status. The meta-analysis also suggested that -169T/C mutation might have positive correlation with risk of RA in the overall population, particularly for Asian. Stratified analysis based on clinical characteristics of RF and ACPA also provided evidence that -169T/C polymorphisms could alter phenotypes of RA. CONCLUSION: The FCRL3 -169T/C variant was significantly linked with an increased RA risk in the Chinese Han population. Moreover, this meta-analysis also provides notion that -169T/C variant could act as a susceptible factor for RA. However, further investigations about the functional impacts of this polymorphism are essential to confirm the above conclusions. | |
26339878 | [Rheumatoid arthritis and combined pulmonary fibrosis and emphysema]. | 2015 | The combination of pulmonary fibrosis and emphysema is a syndrome described in the last years, which has its own characteristics and it is not only the casual association between the two entities. The idiopathic pulmonary fibrosis is the most common type of pulmonary fibrosis. However other interstitial lung diseases could be part of this syndrome. Among them is the connective tissue disease-associated interstitial lung disease. We report a case of this syndrome associated with rheumatoid arthritis. It has the peculiarity that the connective disease became overt several years after the presentation of combined pulmonary fibrosis and emphysema syndrome, which is infrequently reported in the literature. | |
27727050 | Reliability testing of the Larsen and Sharp classifications for rheumatoid arthritis of th | 2017 Jan | BACKGROUND: Two popular systems for classifying rheumatoid arthritis affecting the elbow are the Larsen and Sharp schemes. To our knowledge, no study has investigated the reliability of these 2 systems. We compared the intraobserver and interobserver agreement of the 2 systems to determine whether one is more reliable than the other. METHODS: The radiographs of 45 patients diagnosed with rheumatoid arthritis affecting the elbow were evaluated. Anteroposterior and lateral radiographs were deidentified and distributed to 6 evaluators (4 fellowship-trained upper extremity surgeons and 2 orthopedic trainees). Each evaluator graded all 45 radiographs according to the Larsen and Sharp scoring methods on 2 occasions, at least 2 weeks apart. RESULTS: Overall intraobserver reliability was 0.93 (95% confidence interval [CI], 0.90-0.95) for the Larsen system and 0.92 (95% CI, 0.86-0.96) for the Sharp classification, both indicating substantial agreement. Overall interobserver reliability was 0.70 (95% CI, 0.60-0.80) for the Larsen classification and 0.68 (95% CI, 0.54-0.81) for the Sharp system, both indicating good agreement. There were no significant differences in the intraobserver or interobserver reliability of the systems overall and no significant differences in reliability between attending surgeons and trainees for either classification system. CONCLUSION: The Larsen and Sharp systems both show substantial intraobserver reliability and good interobserver agreement for the radiographic classification of rheumatoid arthritis affecting the elbow. Differences in training level did not result in substantial variances in reliability for either system. We conclude that both systems can be reliably used to evaluate rheumatoid arthritis of the elbow by observers of varying training levels. | |
27118745 | Burning vasculitis. | 2016 Apr 26 | We present the case of a 69-year-old man who was found collapsed close to a heat source and admitted to hospital for severe sepsis. He was also found to have widespread blistering and ulceration of his right leg; however, a history was unobtainable due to reduced consciousness levels. The leg lesions had the initial appearance of mixed depth burns and a management plan was made to transfer the patient to a burns unit for debridement. It was subsequently noted that the patient had a previous diagnosis of seropositive erosive rheumatoid arthritis. A biopsy of the leg lesion was performed and a diagnosis of rheumatoid vasculitis confirmed. Treatment with systemic steroids, intravenous antibiotics and intravenous immunoglobulin therapy for severe hypogammaglobulinaemia was started, and the patient was not transferred for surgical debridement. Rheumatoid vasculitis is a rare and extremely serious complication of rheumatoid arthritis that can manifest in a number of ways, occasionally mimicking other conditions. This case is essential to raise awareness of rare, severe rheumatoid vasculitis and of the potential for its misdiagnosis as a mixed depth burn. | |
27653044 | Arterial stiffness is not increased in patients with short duration rheumatoid arthritis a | 2017 Apr | Patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have increased cardiovascular (CV) morbidity and mortality. Arterial stiffness is an independent predictor of CV events. The aim of the study was to assess arterial stiffness and inflammatory markers in patients with short duration chronic arthritis. We assessed carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), traditional CV risk factors and inflammatory and endothelial markers in 71 chronic arthritis patients (RA and AS) and in 29 healthy controls. We did not find differences in PWV (for RA, AS and controls, respectively: 10 [8.8-10.9] versus 10.7 [9.1-11.8] versus 9.2 [8.3-11.4] m/s; p = .14) and AIx (for RA, AS and controls, respectively: 24.3 ± 11.5 versus 5.7 ± 12.4 versus 10 ± 12.8%; p = .22). Both groups of arthritis patients had active disease with significantly elevated inflammatory markers compared to controls. There were no correlations between endothelial and inflammatory markers and parameters of arterial stiffness in arthritis patients. When analyzing arthritis patients according to median of PVW, there were no significant differences in inflammatory and endothelial markers. We found that in patients with short duration active RA and AS arterial stiffness was not increased and furthermore, there was no association between markers of systemic inflammation and arterial stiffness. | |
27522665 | Methotrexate affects HMGB1 expression in rheumatoid arthritis, and the downregulation of H | 2016 Sep | High-mobility group box 1 (HMGB1) is associated with the development of rheumatoid arthritis (RA). Recent studies have shown that methotrexate (MTX) may inhibit the expression of HMGB1. This study examined whether HMGB1 might be involved in the treatment of RA using MTX. Synovial tissues were collected from RA patients who were treated with MTX for at least 6Â months (RA-MTX group, 7 cases) and from those without MTX treatment (RA-noMTX group, 7 cases). Additionally, patients with osteoarthritis (OA group, 7 cases) were used as controls. The expression and locations of HMGB1 in the tissues were detected using real-time PCR, western blot, and immunohistochemistry. Additionally, OA-fibroblast-like synoviocytes (FLSs) and RA-FLSs were isolated and cultured, and the expression of HMGB1 was reduced in these cells by transfection with HMGB1 siRNA. Cell proliferation, migration, and invasion abilities were detected. Furthermore, the effects of HMGB1 on matrix metalloproteinase (MMP)-2 and MMP-13 were measured using western blot analysis. At the tissue level, HMGB1 expression in synovial membrane did not differ significantly between the OA and RA-MTX groups, but was significantly lower in these groups than in the RA-noMTX group. In cell experiments, the cell doubling time in the RA-FLS HMGB1 siRNA group was significantly extended compared with that in the RA-FLS negative control (NC)-siRNA group. The amount of cell migration and invasion in the RA-FLS HMGB1 siRNA group was significantly lower compared with that in the NC-siRNA group; the MMP-2 and MMP-13 expression levels were also lower. These results showed that MTX reduced HMGB1 expression in RA synovial tissues, and through the downregulation of HMGB1 expression in tissues, MTX may slow disease progression of RA. | |
25370172 | Identifying barriers to smoking cessation in rheumatoid arthritis. | 2015 May | OBJECTIVE: The aim of this study was to investigate disease-related issues that make smoking cessation challenging for patients with rheumatoid arthritis (RA). There is currently a lack of research on tailoring smoking cessation interventions for RA patients. Qualitative exploration is a necessary first step in planning targeted interventions. METHODS: A qualitative mixed-methods study was undertaken. Participants attended either a focus group or an individual interview and completed a set of standardized questionnaires. The sample consisted of 36 RA patients: 24 current smokers and 12 ex-smokers. The transcripts were analyzed thematically using a critical realist approach to inductively identify themes. RESULTS: Five key barriers to smoking cessation that are faced by RA patients were identified. First, participants were unaware of the relationship between smoking and RA and therefore did not perceive this as a reason to quit. Second, smoking was used as a distraction from pain. Third, participants found it difficult to exercise and therefore were unable to use exercise as an alternative distraction. Fourth, smoking was used as a coping mechanism for the frustrations of living with RA. Fifth, participants felt unsupported and isolated from other RA patients. CONCLUSION: Disease-related issues may hinder smoking cessation for RA patients. Through an understanding of patients' perspectives there is an opportunity to plan an effective targeted intervention that may increase the chance of smoking cessation in RA patients where smoking may adversely influence disease progression and comorbidities. | |
26013310 | Comparison of the DAS28-CRP and DAS28-ESR in patients with rheumatoid arthritis. | 2015 Jul | AIM: To compare the Disease Activity Score with 28 joint (DAS28) using erythrocyte sedimentation rate (ESR) (DAS28-ESR) and DAS28 using C-reactive protein (CRP) (DAS28-CRP) with thresholds validated for DAS28-ESR in Turkish patients with rheumatoid arthritis. METHOD: The DAS28 data of 112 patients with rheumatoid arthritis followed in a local outpatient clinic were used. First, the correlation between DAS28-CRP and DAS28-ESR and the correlation between their unique components ([0.36 × In (CRP + 1) + 0.96] and [0.70 × In (ESR)]) were analyzed. Second, a Bland-Altman plot was constructed for the evaluation of the level of agreement between DAS28-CRP and DAS28-ESR. Lastly, the agreement between these two methods was analyzed by κ coefficient. RESULTS: Although there was a strong correlation between DAS28-CRP and DAS28-ESR, the correlation between their unique components was fair. Although more than 95% of the point data fall between the upper and lower bounds of the limit of agreement, the percentage error (46%) was higher than the acceptable proportion of 30%. The κ coefficient of agreement between DAS28- ESR and DAS28-CRP with validated thresholds for DAS28-ESR was 0.42, which was close to the lower boundary for moderate agreement. CONCLUSION: The results of this study demonstrated that there is discordance between DAS28-ESR and DAS28-CRP with the validated thresholds for DAS28-ESR. Using the DAS28-CRP with threshold values validated for DAS28-ESR may lead to errors in the determination of disease activity and therefore may lead to errors in the management of patients with rheumatoid arthritis. | |
28139553 | [Prospects for rheumatoid arthritis pharmacotherapy: New opportunities and recommendations | 2016 | The paper considers a current strategy, international and Russian recommendations for the pharmacotherapy of rheumatoid arthritis (RA), one of the most common and severe human immune-mediated inflammatory diseases. It emphasizes the need for early diagnosis and therapy with disease-modifying antirheumatic drugs, primarily methotrexate (MT), starting at the onset of the disease, and careful monitoring of therapeutic effectiveness, allowing RA remission to be achieved with a treatment-to-target strategy. The author discusses recent RA pharmacotherapy advances that are related to the rational use of MT, biological agents, and the new targeted JAK inhibitor tofacitinib. | |
26350270 | MHC2TA and FCRL3 genes are not associated with rheumatoid arthritis in Mexican patients. | 2016 Feb | Rheumatoid arthritis (RA) is a multifactorial disease. A combination of genetic and environmental risk factors contributes to its etiology. Several genes have been reported to be associated with susceptibility to the development of RA. The MHC2TA and FCRL3 genes have been associated previously with RA in Swedish and Japanese populations, respectively. In two recent reports, we show an association between FCRL3 and juvenile rheumatoid arthritis (JRA), and MHC2TA and acute coronary syndrome (ACS) in Mexican population. We assessed the association between three single nucleotide polymorphisms (SNPs) of the MHC2TA (-168G/A; rs3087456, and +16G/C; rs4774) and FCRL3 (-169T/C; rs7528684) genes and rheumatoid arthritis in Mexican population through a genotyping method using allelic discrimination assays with TaqMan probes. Our case-control study included 249 patients with RA and 314 controls. We found no evidence of an association between the MHC2TA -168G/A and +1614G/C or FCRL3 -169T/C polymorphisms and RA in this Mexican population. In this cohort of Mexican patients with RA, we observed no association between the MHC2TA or FCRL3 genes and this autoimmune disease. | |
27964757 | Discordant inflammation and pain in early and established rheumatoid arthritis: Latent Cla | 2016 Dec 13 | BACKGROUND: Rheumatoid arthritis (RA) disease activity is often measured using the 28-joint Disease Activity Score (DAS28). We aimed to identify and independently verify subgroups of people with RA that may be discordant with respect to self-reported and objective disease state, with potentially different clinical needs. METHODS: Data were derived from three cohorts: (1) the Early Rheumatoid Arthritis Network (ERAN) and the British Society for Rheumatology Biologics Register (BSRBR), (2) those commencing tumour necrosis factor (TNF)-α inhibitors and (3) those using non-biologic drugs. In latent class analysis, we used variables related to pain, central pain mechanisms or inflammation (pain, vitality, mental health, erythrocyte sedimentation rate, swollen joint count, tender joint count, visual analogue scale of general health). Clinically relevant outcomes were examined. RESULTS: Five, four and four latent classes were found in the ERAN, BSRBR TNF inhibitor and non-biologic cohorts, respectively. The proportions of people assigned with >80% probability into latent classes were 76%, 58% and 72% in the ERAN, TNF inhibitor and non-biologic cohorts, respectively. The latent classes displayed either concordance between measures indicative of mild, moderate or severe disease activity; discordantly worse patient-reported measures despite less markedly elevated inflammation; or discordantly less severe patient-reported measures despite elevated inflammation. Latent classes with discordantly worse patient-reported measures represented 12%, 40% and 21% of the ERAN, TNF inhibitor and non-biologic cohorts, respectively; contained more females; and showed worse function. In those latent classes with worse scores at baseline, DAS28 and function improved over 1 year (p < 0.001 for all comparisons), and scores differed less at follow-up than at baseline. CONCLUSIONS: Discordant latent classes can be identified in people with RA, and these findings are robust across three cohorts with varying disease duration and activity. These findings could be used to identify a sizeable subgroup of people with RA who might gain added benefit from pain management strategies. | |
25774559 | Improving medication adherence in rheumatoid arthritis (RA): a pilot study. | 2015 | The aim of this exploratory pilot study was to adapt a psychological intervention to improve adherence to medication for patients with rheumatoid arthritis (RA). The approach draws on cognitive behavioural therapy (CBT) techniques, including motivational interviewing . The current study aimed to (i) adapt the intervention for patients with RA, (ii) assess its effectiveness in improving adherence to medication and (iii) evaluate patients' experience of the intervention. Participants were randomly allocated to either the 'intervention group' (N  =  10), receiving up to six weekly sessions of 'Compliance Therapy', or to the 'wait-list control' group (N  =  8), who received standard care. Data was collected pre intervention (baseline), post intervention and at six weeks post intervention (follow-up). Eighteen female participants with a mean age of 48.78 years (SD 15.12) took part in the study. Comparisons across the two time points for each group found that only those in the 'intervention' group demonstrated significant improvement in mean scores on adherence measures. Between-group comparisons were not significant. The pilot study suggests that an intervention based on CBT may improve adherence in patients with RA, but further research is required. | |
26286007 | Implying Analytic Measures for Unravelling Rheumatoid Arthritis Significant Proteins Throu | 2016 Jun | Rheumatoid arthritis (RA) is a systemic autoimmune and inflammatory disease that mainly alters the synovial joints and ultimately leads to their destruction. The involvement of the immune system and its related cells is a basic trademark of autoimmune-associated diseases. The present work focuses on network analysis and its functional characterization to predict novel targets for RA. The interactive model called as rheumatoid arthritis drug-target-protein (RA-DTP) is built of 1727 nodes and 7954 edges followed the power-law distribution. RA-DTP comprised of 20 islands, 55 modules and 123 submodules. Good interactome coverage of target-protein was detected in island 2 (Q-Score 0.875) which includes 673 molecules with 20 modules and 68 submodules. The biological landscape of these modules was examined based on the participation molecules in specific cellular localization, molecular function and biological pathway with favourable p value. Functional characterization and pathway analysis through KEGG, Biocarta and Reactome also showed their involvement in relation to the immune system and inflammatory processes and biological processes such as cell signalling and communication, glucosamine metabolic process, renin-angiotensin system, BCR signals, galactose metabolism, MAPK signalling, complement and coagulation system and NGF signalling pathways. Traffic values and centrality parameters were applied as the selection criteria for identifying potential targets from the important hubs which resulted into FOS, KNG1, PTGDS, HSP90AA1, REN, POMC, FCER1G, IL6, ICAM1, SGK1, NOS3 and PLA2G4A. This approach provides an insight into experimental validation of these associations of potential targets for clinical value to find their effect on animal studies. | |
26535777 | Serum Sclerostin Level Among Egyptian Rheumatoid Arthritis Patients: Relation to Disease A | 2015 Jul | INTRODUCTION: Bone loss in rheumatoid arthritis is caused by increased bone resorption without increasing bone formation. The Wnt pathway is important in the control of bone formation through the regulation of osteoblast activity. Sclerostin is an important regulator of the Wnt pathway by blocking Wnt binding to its receptor and thereby inhibiting bone formation. AIM: This study aimed to assess the serum sclerostin level in a group of Egyptian rheumatoid arthritis patients and to correlate its level with bone mineral density, disease activity and radiological grading. METHODS: Forty rheumatoid arthritis patients (mean age 48.9 ± 11.6 years, disease duration 8 ± 6.4 years) and 40 age and sex matched apparently healthy subjects were included. Serum sclerostin level was measured using Enzyme linked Immunosorbent Assay. Plain radiographs of hands and feet and dual-energy x-ray absorptiometry test were done for all patients. RESULTS: No significant difference was found between rheumatoid arthritis patients and healthy controls as regard mean value of sclerostin level. Postmenopausal healthy women had higher levels of sclerostin than premenopausal healthy women only. Serum sclerostin had significantly positive correlations with the age of onset and weight of rheumatoid arthritis patients and negative correlation with Erythrocyte Sedimentation Rate. No correlation was encountered between sclerostin level and bone mineral density, disease activity or radiographic grading. CONCLUSION: For better clarification of the role of sclerostin on bone mass in rheumatoid arthritis, larger sample size is needed. More studies on serum sclerostin levels among different grades of RA activity are encouraged. . |
|
27120440 | [Prevalence of rheumatoid arthritis in Germany based on health insurance data : Regional d | 2016 Oct | BACKGROUND: Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease with a prevalence of up to 1 % in the adult population. OBJECTIVE: This study describes the prevalence of RA diagnoses in outpatient health insurance claims data, based on different case definitions and stratified by age, sex and region of residence. METHODS: Based on data from a nationwide statutory health insurance fund (BARMER GEK) from the year 2013, a cross-sectional study of insurants aged 18 years or older was conducted. The following case definitions were applied: A) a diagnosis of seropositive rheumatoid arthritis (M05) or other rheumatoid arthritis (M06) according to the international classification of diseases 10 German modification (ICD-10-GM) in at least two quarterly periods of the year 2013, B) case definition A plus determination of C‑reactive protein (CRP) or erythrocyte sedimentation rate (ESR) at least once, C) case definition B plus specific drug therapy and D) case definition A plus treatment by a rheumatologist. Raw as well as age and sex-standardized prevalences were calculated and stratified according to the federal state. RESULTS: The study population consisted of 7,155,315 insurants of whom 60.2 % were female. Overall, RA prevalences for the respective case definitions were 1.62 % (A), 1.11 % (B), 0.94 % (C) and 0.64 % (D). When standardized to the German population the prevalences were 1.38 % (A), 0.95 % (B), 0.81 % (C) and 0.55 % (D). The proportion of women was approximately 80 % for all case definitions. Prevalences increased with age, peaking in the age group 70-79 years old and showing the highest values in eastern and the lowest in southern Germany for raw as well as standardized measures. CONCLUSION: Regional differences in the prevalence of RA diagnoses in health insurance claims data were observed independent of age, sex and case definition. The expected prevalence according to the results of international studies was best achieved when case definitions with CRP or ESR were considered. | |
26030114 | Targeting NF-κΒ and TNF-α Activation by Electroacupuncture to Suppress Collagen-induced | 2015 Jul | BACKGROUND: Rheumatoid arthritis is an autoimmune disease that can cause chronic inflammation of the joints and other areas of the body. Acupuncture is an emerging alternative therapy for rheumatoid arthritis; however, the molecular mechanism underlying the beneficial effect of acupuncture has not been elucidated. OBJECTIVE: The study aimed to determine the effects of electroacupuncture (EA) on the expression of nuclear factor kappa Β (NF-κΒ) and tumor necrosis factor α (TNF-α) in model rats and to elucidate its anti-inflammatory mechanism in rheumatoid arthritis. DESIGN: The research team conducted a randomized animal study evaluating the efficacies of acupuncture on rheumatoid arthritis. Setting • All processes for the study were conducted at the Hubei University of Chinese Medicine and the Tongji Medical College of the Huazhong University of Science and Technology. Intervention • Twenty rats were randomly selected from 80 male Wistar rats and designated as the normal control (NC) group. The remaining 60 rats were prepared as rheumatoid arthritis models by administering intradermal injections of bovine, type 2 collagen emulsified in incomplete Freund's adjuvant for 3 wk. The 60 rats were randomly divided into 3 groups: (1) a rheumatoid arthritis model (model group); (2) a real-acupuncture-plus model (RA group); and (3) a sham-acupuncture-plus model (SA group), with 20 rats randomly assigned to each group. Zusanli (ST-36), Xuanzhong (GB-39), and Shenshu (BL-23) were applied for treatment of the RA group, whereas sham acupoints were selected for the SA group. OUTCOME MEASURES: The study used ultrastructural observations, an arthritis index, the expression levels of TNF-α and NF-κΒ (p65) in synovial cells, and the content of serum inflammatory cytokines to measure results. RESULTS: The arthritis index, the expression levels of NF-κΒ (p65) and TNF-α in synovial tissues, and the contents of interleukin (IL) 1-β (IL-1β), IL-6, and IL-8 increased for the 3 model groups compared with measurements for the NC group (P < .01). Those parameters were lower for the RA group than for the model group (P < .05). However, no statistically significant difference was observed between the model and SA groups. CONCLUSIONS: Acupuncture mediates the anti-inflammatory NF-kB pathway to reduce disease severity in collagen-induced arthritis. | |
25418518 | To what extent is the familial risk of rheumatoid arthritis explained by established rheum | 2015 Feb | OBJECTIVE: Family history of rheumatoid arthritis (RA) is one of the strongest risk factors for developing RA, and information on family history is, therefore, routinely collected in clinical practice. However, as more genetic and environmental risk factors shared by relatives are identified, the importance of family history may diminish. The aim of this study was to determine how much of the familial risk of RA can be explained by established genetic and nongenetic risk factors. METHODS: History of RA among first-degree relatives of individuals in the Epidemiological Investigation of Rheumatoid Arthritis case-control study was assessed through linkage to the Swedish Multigeneration Register and the Swedish Patient Register. We used logistic regression models to investigate the decrease in familial risk after successive adjustment for combinations of nongenetic risk factors (smoking, alcohol intake, parity, silica exposure, body mass index, fatty fish consumption, and education), and genetic risk factors (shared epitope [SE] and 76 single-nucleotide polymorphisms [SNPs]). RESULTS: Established nongenetic risk factors did not explain familial risk of either seropositive or seronegative RA to any significant degree. Genetic risk factors accounted for a limited proportion of the familial risk of seropositive RA (unadjusted odds ratio [OR] 4.10, SE-adjusted OR 3.72, SNP-adjusted OR 3.46, and SE and SNP-adjusted OR 3.35). CONCLUSION: Established risk factors only provided an explanation for familial risk of RA in minor part, suggesting that many (familial) risk factors remain to be identified, in particular for seronegative RA. Family history of RA therefore remains an important clinical risk factor for RA, the value of which has not yet been superseded by other information. There is thus a need for further etiologic studies of both seropositive and seronegative RA. | |
25943290 | Mast cells in rheumatic disease. | 2016 May 5 | Rheumatoid Arthritis is a chronic autoimmune disease with a complex disease pathogenesis leading to inflammation and destruction of synovial tissue in the joint. Several molecules lead to activation of immune pathways, including autoantibodies, Toll-Like Receptor ligands and cytokines. These pathways can cooperate to create the pro-inflammatory environment that results in tissue destruction. Each of these pathways can activate mast cells, inducing the release of a variety of inflammatory mediators, and in combination can markedly enhance mast cell responses. Mast cell-derived cytokines, chemokines, and proteases have the potential to induce recruitment of other leukocytes able to evoke tissue remodeling or destruction. Likewise, mast cells can secrete a plethora of factors that can contribute to tissue remodeling and fibroblast activation. Although the functional role of mast cells in arthritis pathogenesis in mice is not yet elucidated, the increased numbers of mast cells and mast cell-specific mediators in synovial tissue of rheumatoid arthritis patients suggest that mast cell activation in rheumatoid arthritis may contribute to its pathogenesis. |