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ID PMID Title PublicationDate abstract
28726020 Patterns of circulatory and peripheral blood mononuclear cytokines in rheumatoid arthritis 2017 Oct An imbalance in pro- and anti-inflammatory cytokines is suggested to contribute to tissue damage in rheumatoid arthritis (RA). This study was aimed at investigating profiles of cytokines in circulation and cytokines produced by mitogen-stimulated peripheral blood mononuclear cells (PBMC) in RA patients and healthy controls, and to explore correlations of cytokines with disease activity. Our aim was to identify patterns of cytokine expression as possible indicators of disease activity. Levels of plasma cytokines and PBMC-secreted cytokines were estimated in 26 female RA patients and 28 controls. Five pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6, IL-17, IL-12) and three anti-inflammatory cytokines (IL-4, IL-10, IL-13) were assayed in a multiplex ELISA. RA patients had significantly higher plasma levels of TNF-α, IL-12, and IL-4 compared to healthy controls. On the other hand, mitogen-activated PBMC secreted significantly higher levels of the pro-inflammatory cytokines TNF-α, IFN-γ, IL-17, and IL-12, but lower levels of the anti-inflammatory cytokine IL-10 in RA compared to healthy subjects. The ratios TNF-α/IL-10, IFN-γ/IL-10, IL-17/IL-10, IL-12/IL-10, and IFN-γ/IL-13 were significantly higher in RA patients compared to healthy controls. The range and expression of cytokines were higher in PBMC than in the plasma in all the groups studied. Multivariate pattern analysis of eight cytokines revealed a prediction accuracy of 69% in differentiating RA patients from healthy controls, and of 73% in classifying patients as in remission or active RA. Our data suggest that it is worthwhile to explore ratios of pro- to anti-inflammatory cytokines produced by mitogen-stimulated PBMC in RA, and the use of multivariate cytokine pattern and algorithms for better delineation of this condition.
28067317 Glucose-6-Phosphate Isomerase (G6PI) Mediates Hypoxia-Induced Angiogenesis in Rheumatoid A 2017 Jan 9 The higher level of Glucose-6-phosphate isomerase (G6PI) has been found in both synovial tissue and synovial fluid of rheumatoid arthritis (RA) patients, while the function of G6PI in RA remains unclear. Herein we found the enrichment of G6PI in microvascular endothelial cells of synovial tissue in RA patients, where a 3% O(2) hypoxia environment has been identified. In order to determine the correlation between the high G6PI level and the low oxygen concentration in RA, a hypoxia condition (~3% O(2)) in vitro was applied to mimic the RA environment in vivo. Hypoxia promoted cellular proliferation of rheumatoid arthritis synovial fibroblasts (RASFs), and induced cell migration and angiogenic tube formation of human dermal microvascular endothelial cells (HDMECs), which were accompanied with the increased expression of G6PI and HIF-1α. Through application of G6PI loss-of-function assays, we confirmed the requirement of G6PI expression for those hypoxia-induced phenotype in RA. In addition, we demonstrated for the first time that G6PI plays key roles in regulating VEGF secretion from RASFs to regulate the hypoxia-induced angiogenesis in RA. Taken together, we demonstrated a novel pathway regulating hypoxia-induced angiogenesis in RA mediated by G6PI.
25865479 Computer-based measurements of joint space analysis using metacarpal morphometry in hand r 2017 Sep AIM AND OBJECTIVES: The aim and objectives are as follows: (i) to perform an automated segmentation of the hand from radiographs using a dual tree complex wavelet-based watershed algorithm; ii) to compare the measured statistical features of the joint space of the hand using gray level co-occurrence matrix (GLCM) method with standard diagnostic parameters of rheumatoid arthritis (RA). METHODS: Fifty-three patients with RA and 17 age- and sex-matched healthy controls were included in the study. The erythrocyte sedimentation rate (ESR), C-reactive protein, rheumatoid factor, health assessment questionnaire score (HAQ), disease activity score (DAS) and hand radiographs of all the subjects were obtained. Joint space width and cortical thickness were measured in metacarpophalangeal joints (MCP) and metacarpal bone semi-automatically using MIMICS software. Dual tree complex wavelet transform-based watershed algorithm was applied for automated segmentation, and feature extraction was performed using the GLCM method in hand radiographs of the total population. RESULTS: In the RA group (n = 53), the joint space width measured in the MCP1, MCP3, MCP5 of the hand were reduced significantly (P < 0.01) by 16.4%, 15.6%, and 17.5%, respectively compared to the normal group (n = 17). The measured combined cortical thickness at the second, third and fourth metacarpal bones of the hand were reduced significantly (P < 0.01) by 9.5%, 12% and 8%, respectively in the RA group compared to the normal group. CONCLUSION: The dual tree complex wavelet transform-based watershed algorithm provided effective segmentation in the digitized hand radiographs. The standard diagnostic parameters for RA were highly correlated with measured statistical features at MCP3 hand joint in the total population studied.
28871338 Comparison of the effectiveness on intra-articular and subcutaneous TNF inhibitor in rheum 2018 Jan The objective of this study is to evaluate the efficacy of single intra-articular (IA) injection of tumor necrosis factor α (TNFα) inhibitor in knee joints comparing with subcutaneous injection in rheumatoid arthritis (RA) patients. Forty-eight RA patients with 73 knee arthritis were divided into three groups, group A: received a single injection of TNF inhibitor into knee joints; group B: received regular subcutaneous injection; and group C: received both of the regimen as groups A and B. Ultrasound, erythrocyte sedimentation rate, C-reactive protein (CRP), patients' global visual analogue scale (VAS), and 28-joint Disease Activity Score (DAS28) were collected pre- and post-therapy 4 weeks. The results of the study are as follows: (1) CRP, VAS, and DAS28 of all groups improved significantly post-therapy (p < 0.05); (2) After therapy, synovial hypertrophy (SH) decreased significantly from 4.40 ± 1.86 mm to 2.74 ± 1.88 mm (p < 0.05) and power Doppler (PD) signal decreased significantly from 2.63 ± 0.75 to 1.50 ± 0.93 (p < 0.01) in group A. Synovial effusion (SE), SH, and PD showed no significant improvement in group B. SE decreased significantly from 9.84 ± 4.70 mm to 5.89 ± 4.47 mm (p < 0.05), SH decreased significantly from 4.52 ± 1.97 mm to 2.49 ± 1.73 mm (p < 0.01), and PD decreased significantly from 2.46 ± 0.66 to 1.38 ± 1.04 (p < 0.01) in group C; and (3) The improvement rate of SH and PD in both groups A and C was obviously higher than that of group B (p < 0.05). Single IA injection of TNFα inhibitor was an effective treatment in improvement of SH and PD of knee joints than subcutaneous injection in RA patients.
29148413 Variable impacts of different remission states on health-related quality of life in rheuma 2018 Mar OBJECTIVES: Targeting remission in rheumatoid arthritis (RA) improves health-related quality of life (HRQoL) and disability. However, the impacts of different remission criteria and durations and their frequencies are uncertain. Our observational study assessed these factors. METHODS: We recruited RA patients with disease durations <10 years, stable suppressive therapies and stable disease activity scores for 28 joints using ESR (DAS28-ESR) ≤3.2. Intermittent and sustained remisisons were classified using DAS28ESR, simple disease activity index (SDAI) and ACR/EULAR Boolean criteria. HRQoL, measured using SF-36, fatigue, EuroQol and health assessment questionnaire (HAQ) was compared using time-integrated areas under the curve (AUC). RESULTS: 104 patients were enrolled and followed for 12 months. DAS28-ESR remissions were intermittent in 42%, sustained in 47% and absent in 11%. Boolean remissions were intermittent in 38%, sustained in 10% and absent in 52%. Baseline remissions by all criteria significantly improved HAQ, Euroqol, SF36 and fatigue scores compared with low disease activity (LDAS); AUCs showed significant benefits for all HRQoLs persisted over 12-months. Boolean remissions achieved most benefits. Over time all remission states gave significantly better HRQoL scores than LDAS. Sustained DAS28ESR and SDAI remissions improved HRQoL more than intermittent remissions. Sustained and intermittent Boolean remissions gave similar improvements. Analysis of SF-36 domains showed even sustained Boolean remissions failed to optimise pain and fatigue. CONCLUSIONS: All remissions improve HRQoL but different criteria have variable impacts. Boolean remission had most impact but occurred least. There are trade-off between optimising individual impacts (Boolean remissions) and achieving maximal overall impacts (DAS28-ESR remissions).
28900117 Dextromethorphan Exhibits Anti-inflammatory and Immunomodulatory Effects in a Murine Model 2017 Sep 12 Dextromethorphan (d-3-methoxy-17-methylmorphinan, DXM) is a commonly used antitussive with a favorable safety profile. Previous studies have demonstrated that DXM has anti-inflammatory and immunomodulatory properties; however, the effect of DXM in rheumatoid arthritis (RA) remains unknown. Herein, we found that DXM treatment attenuated arthritis severity and proinflammatory cytokine expression levels, including TNF-α, IL-6, and IL-17A, in paw tissues of CIA mice. DXM treatment also reduced serum TNF-α, IL-6, and IL-17A levels of CIA mice and patients with RA. DXM further decreased the production of anti-CII IgG, IFN-γ, and IL-17A in collagen-reactive CD4(+) T cells extracted from the lymph nodes of CIA mice. In vitro incubation of bone marrow-derived dendritic cells with DXM limited CD4(+) T-cell proliferation and inflammatory cytokine secretion. In conclusion, our results showed that DXM attenuated arthritis symptoms in CIA mice and significantly reduced proinflammatory cytokines in patients with RA, suggesting that it can be used as an anti-arthritic agent.
28028155 Abatacept reduces disease activity and ultrasound power Doppler in ACPA-negative undiffere 2017 Jan OBJECTIVES: No proven treatment exists for ACPA-negative undifferentiated arthritis (UA). The aim of this study was to evaluate whether abatacept is effective in treating poor prognosis, ACPA-negative UA, including its effect on power Doppler on US (PDUS). METHODS: A proof-of-concept, open-label, prospective study of 20 patients with DMARD-naïve, ACPA-negative UA (⩾2 joint synovitis) and PDUS ⩾ 1 with clinical and 20-joint US (grey scale/PDUS) assessments at baseline, 6, 12, 18 and 24 months. All patients received 12 months of abatacept (monotherapy for minimum first 6 months). The primary end point was a composite of the proportion of patients that at 6 months achieved DAS44 remission, a maximum of one swollen joint for at least 3 consecutive months and no radiographic progression (over 0-12 months). RESULTS: Twenty of the 23 patients screened were enrolled [14 female; mean (sd) age 53.4 (11.2) years, symptom duration 7.5 (0.9) months]. Two (10%) achieved the composite primary end point. A reduction in the mean (sd) DAS44 was observed from a baseline value of 2.66 (0.77) to 2.01 (0.81) at 6 months and to 1.78 (0.95) at 12 months. The DAS44 remission rates were 6/20 (30%; 95% CI: 15, 51%) at 6 months and 8/20 (40%; 95% CI: 22, 62%) at 12 months. A striking decrease in the median (interquartile range; IQR) total PDUS score was noted from 10 (4-23) at baseline to 3 (2-12) and 3 (0-5) at 6 and 12 months, respectively. CONCLUSION: This report is a first in potentially identifying an effective therapy, abatacept monotherapy, for poor-prognosis, ACPA-negative UA, supported by a clear reduction in PDUS. These data justify evaluation in a controlled study.
28522406 Therapeutic effect of Cryptotanshinone on experimental rheumatoid arthritis through downre 2017 Aug 15 BACKGROUND AND PURPOSE: The balance between T helper 17 (Th17) cells and regulatory T (Treg) cells, plays a critical role in rheumatoid arthritis (RA). The differentiation of Th17 cells requires the activation of STAT3, which determines the balance of Th17/Treg. Here, we investigated the therapeutic effect of Cryptotanshinone (CTS) on collagen induced mouse arthritis and explored the underlying mechanisms. EXPERIMENTAL APPROACH: Arthritis was induced in DBA/1 mice with bovine collagen type II and complete Freund's adjuvant. CTS was given at 20mgkg(-1)d(-1) or 60mgkg(-1)d(-1) by gavage for 6weeks. The immuno-inflammation and joint destruction were evaluated and the balance of Th17/Treg was determined. STAT3 acetylation and phosphorylation were detected by western blotting, and the involvement of p300 was investigated by siRNA and plasmid overexpression. KEY RESULTS: CTS at a dose of 60mgkg(-1)d(-1) ameliorated the inflammation and joint destruction in CIA mice. It improved Th17/Treg imbalance, and inhibited both acetylation and phosphorylation of STAT3. CTS reduced p300 expression and its binding to STAT3, but increased phosphorylated AMPK. Knockdown of p300 mimicked the inhibitory effect of CTS on STAT3 acetylation and phosphorylation, which could be partially rescued by overexpression of p300-WT, but not p300-dominant negative (DN) construct. CONCLUSION AND IMPLICATIONS: Our study suggested that the anti-arthritis effects of CTS were attained through suppression of p300-mediated STAT3 acetylation. Our data suggest that CTS might be a potential immune modulator for RA treatment.
28978352 Assessment of 3-month changes in bone microstructure under anti-TNFα therapy in patients 2017 Oct 4 BACKGROUND: Although one study showed minimal progression of erosions in patients with rheumatoid arthritis (RA) one year after TNFα inhibition therapy, no studies have investigated very early bone changes after initiation of anti-TNFα treatment. We investigated the effects of 3-month anti-TNFα treatment on bone erosion progression and bone microarchitecture in RA patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Patients with RA (n = 27) (17 in the anti-TNFα and 10 in the MTX-only group) underwent assessment of disease activity score in 28 joints (DAS-28), radiographs, 3-T magnetic resonance imaging (MRI) and HR-pQCT of metacarpophalangeal and wrist joints at baseline and 3 months. HR-pQCT-derived erosion volume, joint volume/width and bone microarchitecture were computed and joint destruction was assessed using Sharp and RAMRIS scorings on radiographs and MRI, respectively. RESULTS: Overall, 73 erosions were identified by HR-pQCT at baseline. Over 3 months, the anti-TNFα group had decreased mean erosion volume; increased erosion volume was observed in one clinical non-responder. The MTX-only group in contrast, trended toward increasing erosion volume despite low disease activity. In the anti-TNFα group, joint-space width and volume of MCP joints decreased significantly and was positively correlated with erosion volume changes (R (2) = 0.311, p = 0.013; R (2) = 0.527, p = 0.003, respectively). In addition, erosion volume changes were significantly negatively correlated with changes in trabecular bone mineral density (R (2) = 0.353, p = 0.020) in this group. We observed significant correlation between percentage change in erosion volume and change in DAS-28 erythrocyte sedimentation rate and C-reactive protein CRP scores (R (2) = 0.558, p < 0.001; R (2) = 0.745, p < 0.001, respectively) in all patients. CONCLUSIONS: Using HR-pQCT, our data suggest that anti-TNFα treatment prevents erosion progression and deterioration of bone microarchitecture within the first 3 months of treatment, one patient not responding to treatment, had significant progression of bone erosions within this short time period. Patients with low disease activity scores (<3.2) can have continuous HR-pQCT-detectable progression of erosive disease with MTX treatment only. HR-pQCT can be a sensitive, powerful tool to quantify bone changes and monitor RA treatment short term (such as 3 months).
28846523 Performing Pain and Inflammation: Rendering the Invisible Visible. 2017 Aug 1 These drawings represent everyday experiences of an artist who has been living with rheumatoid arthritis since her teenage years. Over the course of 20 years, the disease has damaged a series of joints in her body. Pain and inflammation accompany the most mundane of her movements and gestures. Fatigue and side effects of medications are routine parts of life. None of her impairments are publicly recognized and duly accommodated, as she is not (yet) visibly disabled. Asking for a seat on the bus, for instance, turns into a thorough social negotiation, as does having to constantly remind people that she actually is disabled. Lacking visual signs of disability, she is often accosted for "evidence"-an authentication, a reminder of "her" disability. With these drawings, each of which describes the artist's daily negotiations with pain, inflammation, and fatigue, she seeks to render visible what remains locked up within the boundaries of her skin.
29167154 Implementation of the EULAR cardiovascular risk management guideline in patients with rheu 2018 Apr The updated European League Against Rheumatism (EULAR) guideline recommends cardiovascular disease (CVD) risk assessment at least once every 5 years in all patients with rheumatoid arthritis (RA). This viewpoint starts with a literature overview of studies that investigated the level of CVD risk factor (CVD-RF) screening in patients with RA in general practices or in outpatient clinics. These studies indicate that CVD-RF screening in patients with RA is marginally applied in clinical practice, in primary as well as secondary care. Therefore, the second part of this viewpoint describes an example of the successful implementation of the EULAR cardiovascular disease risk management (CVRM) guideline in patients with RA in a region in the south of the Netherlands where rheumatologists and general practitioners (GPs) closely collaborate to manage the cardiovascular risk of patients with RA. The different components of this collaboration and the responsibilities of respectively primary and secondary care professionals are described. Within this collaboration, lipid profile was used as an indicator to assess whether CVD-RF screening was performed in the previous 5 years. In 72% (n=454) of the 628 patients with RA, a lipid profile was determined in the previous 5 years. As part of routine quality control, a reminder was sent to the GP in case a patient with RA was not screened. After sending the reminder letter, in 88% of all patients with RA, CVD risk assessment was performed. This collaboration can be seen as good practice to provide care in line with the EULAR guideline.
29288974 Jobelyn(®) attenuates inflammatory responses and neurobehavioural deficits associated wit 2018 Feb Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the physical and psychosocial wellbeing of the patients and a major cause of work disability. Current drugs for its treatment only provide palliative effect, as cure for the disease still remains elusive. Jobelyn(®) (JB), a potent anti-oxidant and anti-inflammatory dietary supplement obtained from Sorghum bicolor, has been claimed to relieve arthritic pain. Thus, this study was designed to evaluate its effect on inflammatory and biochemical changes as well as neurobehavioural deficits associated with complete Freund-adjuvant (CFA)-induced arthritis in mice. The effect of JB (50, 100 and 200 mg/kg) on inflammatory oedema, neurobehavioural deficits, levels of biomarkers of oxidative stress and inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) induced by 0.1 mL of CFA (10 mg/mL) was evaluated in male Swiss mice. Oral administration of JB (100 and 200 mg/kg) reduced inflammatory paw volume and reversed sensorimotor deficits induced by CFA. JB also reduced pain episodes, anxiety and depressive-like symptoms in CFA-mice. The increased level of oxidative stress in the joint and brain tissues of CFA-mice was reduced by JB. It also decreased tumor necrosis factor-alpha and interleukin-6 levels induced by CFA in the joint tissue of mice. These findings suggest that Jobelyn(®) attenuates inflammatory responses induced by CFA in mice via inhibition of oxidative stress and release of inflammatory cytokines. The ability of JB to attenuate CFA-induced nociception, sensorimotor deficits and depressive-like symptom suggests it might improve the quality of life of patients with arthritic conditions.
28482933 Models solely using claims-based administrative data are poor predictors of rheumatoid art 2017 May 8 BACKGROUND: This study developed and validated a claims-based statistical model to predict rheumatoid arthritis (RA) disease activity, measured by the 28-joint count Disease Activity Score (DAS28). METHOD: Veterans enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry with one year of data available for review before being assessed by the DAS28, were studied. Three models were developed based on initial selection of variables for analyses. The first model was based on clinically defined variables, the second leveraged grouping systems for high dimensional data and the third approach prescreened all possible predictors based on a significant bivariate association with the DAS28. The least absolute shrinkage and selection operator (LASSO) with fivefold cross-validation was used for variable selection and model development. Models were also compared for patients with <5 years to those ≥5 years of RA disease. Classification accuracy was examined for remission (DAS28 < 2.6) and for low (2.6-3.1), moderate (3.2-5.1) and high (>5.1) activity. RESULTS: There were 1582 Veterans who fulfilled inclusion criteria. The adjusted r-square for the three models tested ranged from 0.221 to 0.223. The models performed slightly better for patients with <5 years of RA disease than for patients with ≥5 years of RA disease. Correct classification of DAS28 categories ranged from 39.9% to 40.5% for the three models. CONCLUSION: The multiple models tested showed weak overall predictive accuracy in measuring DAS28. The models performed poorly at predicting patients with remission and high disease activity. Future research should investigate components of disease activity measures directly from medical records and incorporate additional laboratory and other clinical data.
29148420 The expression of mRNA for peptidylarginine deiminase type 2 and type 4 in bone marrow CD3 2018 Mar OBJECTIVES: Antibodies directed to citrullinated proteins are highly specific for rheumatoid arthritis (RA). Citrullination is catalyzed by peptidylarginine deiminase (PAD) enzymes. The current study examined the mRNA expression of PADI2 and PADI4 in bone marrow (BM) CD34+ cells from RA patients. METHODS: CD34+ cells were purified from BM samples obtained from 48 RA patients and from 30 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest. The expression of mRNAs for PADI2, PADI4 and Sp1 was examined by quantitative reverse transcription PCR. RESULTS: The expression of mRNA for PADI2 was significantly higher in RA BM CD34+ cells than OA BM CD34+ cells. The expression of mRNAs for PADI4 and Sp1 in RA BM CD34+ cells appeared to be increased compared to OA BM CD34+ cells, although it did not reach the statistical significance. The levels of mRNAs for PADI2, PADI4 and Sp1 were not correlated with serum C-reactive protein or with the administration of methotrexate or oral steroids. Finally, the level of PADI2 mRNA as well as that of PADI4 mRNA was significantly correlated with the level of Sp1 mRNA in RA BM CD34+ cells. CONCLUSIONS: These results indicate that the mRNA expression of PADI2, PADI4 and Sp1 is upregulated in RA BM CD34+ cells independently of the systemic inflammation or treatment regimen. Moreover, the data suggest that the enhanced mRNA expression of PADI2 and PADI4 in BM CD34+ cells might be a result of the enhanced expression of Sp1 gene in RA BM CD34+ cells.
29029330 The association between omega-3 fatty acid biomarkers and inflammatory arthritis in an ant 2017 Dec 1 OBJECTIVES: Higher circulating omega-3 fatty acids (n-3 FAs) are associated with a lower prevalence of anti-CCP antibodies and RF in subjects without RA. We examined whether, in anti-CCP+ subjects, n-3 FAs also play a role in development of inflammatory arthritis (IA). METHODS: At Colorado-based health fairs from 2008 to 2014, participants without a previous diagnosis of RA who were anti-CCP3+ (n = 47) were recruited into a follow-up study; symptom assessments and joint examinations were conducted every 6 months for the determination of IA. We measured n-3 FAs as a percentage of total lipids in red blood cell membranes (n-3 FA%) at each visit. RESULTS: We detected IA in 10 anti-CCP3+ subjects (21%) at the baseline visit. Increased total n-3 FA% in red blood cell membranes [odds ratio (OR) = 0.09, 95% CI: 0.01, 0.76], specifically docosapentaenoic acid (OR = 0.16, 95% CI: 0.03, 0.83) and docosahexaenoic acid (OR = 0.23, 95% CI: 0.06, 0.86), was associated with a lower odds of IA at the baseline visit, adjusting for n-3 FA supplement use, current smoking, RF+, elevated CRP+ and shared epitope. We followed 35 of the anti-CCP3+ subjects who were IA negative at baseline and detected 14 incident IA cases over an average of 2.56 years of follow-up. In a time-varying survival analysis, increasing docosapentaenoic acid significantly decreased risk of incident IA (hazard ratio = 0.52, 95% CI: 0.27, 0.98), adjusting for age at baseline, n-3 FA supplement use, RF+, CRP+ and shared epitope. CONCLUSION: n-3 FAs may potentially lower the risk of transition from anti-CCP positivity to IA, an observation that warrants further investigation.
28459968 Human Leukocyte Antigen Shared Epitope and Inflammation, Cardiovascular Disease, Cancer, a 2017 Jul 15 Specific alleles of the human leukocyte antigen (HLA)-DRB1 gene (HLA-DRB1) encode a "shared epitope" (SE) associated with rheumatoid arthritis (RA), especially more severe cyclic-citrullinated peptide antibody-positive (anti-CCP+) RA. We evaluated associations of number of SE alleles (0, 1, or 2) with total and cardiovascular disease (CVD) mortality and incident coronary heart disease (CHD), CVD, and cancer over a mean 8.9 (standard deviation, 3.5) years of follow-up, stratifying by baseline anti-CCP status (positive (+) vs. negative (-)). A longitudinal study, the Women's Health Initiative RA Study (1993-2010), sampled postmenopausal women who reported RA at baseline (1993-1998) or follow-up in the Women's Health Initiative, classified as anti-CCP+ RA (n = 556) or anti-CCP- non-RA (n = 1,070). Among anti-CCP+ RA women, SE alleles were not related to age-adjusted risks of CHD, CVD, or cancer or to total or CVD mortality. Among anti-CCP- non-RA women, age-adjusted hazard ratios for 1 and 2 SE alleles versus 0 SE alleles were 0.41 (95% confidence interval (CI): 0.34, 0.50) and 0.44 (95% CI: 0.27, 0.72), respectively, for CVD; 0.43 (95% CI: 0.37, 0.53) and 0.30 (95% CI: 0.16, 0.64), respectively, for CHD; and 0.62 (95% CI: 0.53, 0.73) and 0.52 (95% CI: 0.33, 0.83), respectively, for cancer. Associations persisted after adjustment for CVD risk factors, joint pain, rheumatoid factor positivity, and inflammatory markers (white blood cell count or cytokine level). In future studies, investigators should evaluate SE associations among anti-CCP- adults without RA and potential mechanisms.
28255205 The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoi 2017 Rheumatoid arthritis (RA) is a complex and not fully understood autoimmune disease associated with multijoint damage. The main effector cells, the synovial fibroblasts, are apoptosis resistant and hyperplastic which indicate that autophagy level is high in synovial tissue. Real-time PCR, immunocytochemistry, and western blotting were used in this paper to study the autophagy status of the synovial tissues obtained from RA and OA patients at the time of joint replacement surgery. We further evaluated the correlation between autophagy levels with RA activity-associated serum markers with SPSS. The results showed that the expression levels (both in mRNA and in protein level) of autophagy-related proteins (belcin1, Atg5, and LC3) in the synovial tissue of patients with active rheumatoid arthritis (n = 20) were significantly higher than those in OA patients (n = 16). We further showed that the LC3-II/β-actin relative gray value was strongly correlated with the serum levels of several RA activity-related markers: CRP, ESR, CCP, and RF. Our results indicate that evaluating the autophagy level of synovial biopsies might be a useful way to diagnose RA and to estimate the disease activity. Reducing the expression level of autophagy-related genes might become a new therapeutic target for active rheumatoid arthritis.
28401820 [A man with a curved deformity of the hand]. 2017 A 63-year-old male was seen at the rheumatology outpatient clinic because of a curved deformity of his left hand, with fixed flexion of the MCP joints and hyperextension of the PIP and DIP joints. This so-called striatal hand, a feature of Parkinson's disease, can easily be confused with rheumatoid arthritis or Dupuytren's contracture.
29382430 [Genetic polymorphisms of ARL15 and HLA-DMA are associated with rheumatoid arthritis in Ha 2017 Dec Objective To establish the methods for detecting single nucleotide polymorphisms (SNPs) of ADP-ribosylation factor-like GTPase 15 (ARL15), major histocompatibility complex class II-DM alpha (HLA-DMA ) and nuclear factor kappa B subunit 2 (NFKB2) genes using high resolution melting (HRM) technology, and to explore the association of those SNPs with the susceptibility of rheumatoid arthritis (RA) in northwestern Han Chinese population. Methods The PCR-HRM detection system for four SNPs (rs255758, rs1063478, rs397514331 and rs397514332) was established for genotyping, and gene sequencing was performed to validate the genotyping ability of the system. 588 RA cases and 200 controls were enrolled in a case-control study to analyze the associations of ARL15 and HLA-DMA gene polymorphisms with RA risk. Results The direct sequencing validated that the established PCR-HRM detection system could be used for genotyping clinical samples correctly. The mutated genotype of rs397514331 and rs397514332 from NFKB2 gene are not found in this study. The genotype frequencies of rs255758 and rs1063478 had statistical difference between the cases and controls, but no statistical difference in allelic frequencies. Under the dominant model (AA vs AC/CC), the AA genotype of rs255758 decreases the RA risk (OR=0.666, 95%CI=0.478-0.927, P=0.016). Conclusion The method of PCR-HRM we established can be applied to the routine detection of rs255758, rs1063478, rs397514331 and rs397514332. The ARL15 and HLA-DMA gene polymorphisms are associated with RA risk in Northwestern Han Chinese population.
28282578 Aberrant methylation patterns affect the molecular pathogenesis of rheumatoid arthritis. 2017 May This study aims to investigate DNA methylation signatures in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA), and to explore the relationship with transcription factors (TFs) that help to distinguish RA from osteoarthritis (OA). Microarray dataset of GSE46346, including six FLS samples from patients with RA and five FLS samples from patients with OA, was downloaded from the Gene Expression Omnibus database. RA and OA samples were screened for differentially methylated loci (DMLs). The corresponding differentially methylated genes (DMGs) were identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis. A transcriptional regulatory network was built with TFs and their corresponding DMGs. Overall, 280 hypomethylated loci and 561 hypermethylated loci were screened. Genes containing hypermethylated loci were enriched in pathways in cancer, ECM-receptor interaction, focal adhesion and neurotrophin signaling pathways. Genes containing hypomethylated loci were enriched in the neurotrophin signaling pathway. Moreover, we found that CCCTC-binding factor (CTCF), Yin Yang 1 (YY1), v-myc avian myelocytomatosis viral oncogene homolog (c-MYC), and early growth response 1 (EGR1) were important TFs in the transcriptional regulatory network. Therefore, DMGs might participate in the neurotrophin signaling pathway, pathways in cancer, ECM-receptor interaction and focal adhesion pathways in RA. Furthermore, CTCF, c-MYC, YY1, and EGR1 may play important roles in RA through regulating DMGs.