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ID PMID Title PublicationDate abstract
25524204 Rheumatoid arthritis and the alpha-chemokine IP-10. 2014 Interferon(IFN)-gamma-induced protein 10 (IP-10) and its receptor, CXCR3, appear to contribute to the pathogenesis of rheumatoid arthritis (RA). IP-10 has been detected in sera, synovial fluid (SF), and synovial tissue in RA patients. IP-10 is mainly expressed by infiltrating macrophage-like cells and fibroblast-like synoviocytes in RA synovium. The elevated expression of CXCR3 on T cells from SF has been associated with high levels of IFN-gamma, which suggest a preferential Th1 phenotype. A human phase II clinical trial using an anti-IP-10 monoclonal antibody (MDX-1100) for RA patients who had an inadequate response to methotrexate treatment has shown that blocking IP-10 significantly increased response rate compared to the placebo group, suggesting a possible therapeutic use in humans.
22451025 Relationship between sonographic parameters and YKL-40 levels in rheumatoid arthritis. 2013 Feb YKL-40, also known as human cartilage glycoprotein 39, is a member of the "mammalian chitinase-like proteins" family without chitinase activity. Increased serum concentrations are associated with inflammatory processes and several types of cancer. In this study, we evaluated YKL-40 levels in serum and synovial fluid of patients with rheumatoid arthritis in comparison with the ultrasonographic findings. YKL-40 levels were measured by enzyme-linked immunosorbent assay in 25 patients with active rheumatoid arthritis and in 40 healthy subjects. B mode and power Doppler were performed to determine synovial thickening and vascularization. Serum YKL-40 level in patients was significantly higher than the concentration in healthy controls (P < 0.01). In patients with rheumatoid arthritis, the level of the glycoprotein in synovial fluid was remarkably elevated compared to the serum level (P = 0.003). The B mode and power Doppler scores correlated to YKL-40 in serum and synovial fluid (P = 0.07). Serum YKL-40 levels were related positively to serum markers of inflammation such as C-reactive protein (P = 0.004) and erythrocyte sedimentation rate (P = 0.003). This study is the first to demonstrate a relationship between YKL-40 levels and ultrasonographic examinations in Bulgarian patients with rheumatoid arthritis. The findings suggest that YKL-40 might be implicated in the pathogenesis of the disease and could indicate the level of joint inflammation.
22669596 Significant improvement in MRI-proven bone edema is associated with protection from struct 2013 Mar OBJECTIVE: To identify the value of magnetic resonance imaging (MRI)-proven bone edema in patients with very early rheumatoid arthritis (RA). METHODS: All of the 13 patients included in the study were positive at entry for MRI-proven bone edema of the wrist and finger joints and anti-cyclic citrullinated peptide antibodies or IgM-rheumatoid factor. A tight control approach was applied for 12 months. Plain MRI and radiographs of both wrist and finger joints were examined every 6 months. MRI was scored by the RA MRI scoring (RAMRIS) technique and plain radiographs were scored using the Genant-modified Sharp score. Variables that were correlated with plain radiographic changes at 12 months were examined. RESULTS: Simplified disease activity index (SDAI) remission was achieved in 7 patients, and a significant reduction in the RAMRIS bone edema score, which declined to <33 % as compared with the baseline, was achieved in 8 out of 13 patients. Four patients showed plain radiographic progression while 9 patients did not. Significant reductions in the RAMRIS bone edema score (p = 0.007) and the time-integrated SDAI (p = 0.031) were the variables involved in plain radiographic progression. CONCLUSIONS: Improvement in bone edema may be associated with protection against structural damage in very early RA patients managed using the tight control approach.
24803297 Increased serum GP88 (Progranulin) concentrations in rheumatoid arthritis. 2014 Oct GP88 (Progranulin; PGRN) is a secreted glycosylated protein with important functions in several processes, including immune response and cancer growth. Recent reports have shown that PGRN is a therapeutic target for rheumatoid arthritis (RA) because of its capability to bind with tumor necrosis factor receptor (TNFR). However, the serum PGRN level in RA patients has not been investigated. We used enzyme-linked immunosorbent assay (ELISA) to quantify the serum levels of PGRN in 417 healthy subjects, 56 patients with RA and 31 patients with osteoarthritis (OA). In RA patients, we also measured the serum TNF-α and sTNFR concentration. Immunohistochemical staining of PGRN was performed using synovectomy tissue of RA patients. The serum PGRN normal range was established as 40.1 ± 8.7 ng/ml. PGRN levels were not influenced by sex or age. A significant increase in serum PGRN levels was observed in RA (50.2 ± 11.1 ng/ml) and OA (45.4 ± 6.6 ng/ml) groups compared to those in age-matched healthy controls (40.4 ± 9.9 ng/ml) (p<0.05, Tukey). Further, PGRN levels in the synovial fluid of RA patients (68.4 ± 3.4 ng/ml) were found to be significantly higher than those in OA patients (35.9 ± 16.8 ng/ml). Immunohistochemical staining of PGRN revealed that the highest positive signal was detected in macrophages. Circulating PGRN in RA patients was weakly associated with TNF-α and sTNFR 2 concentration. Furthermore, PGRN/TNF-α ratio was correlated the stage of the disease in RA patients. The concentrations of serum PGRN in RA were found to be significantly higher than those in age-matched healthy controls, although it remains to be clarified how blood PGRN is related to the pathogenesis of RA. Our results showed that the serum PGRN may be a useful approach to monitor the disease activity in RA patients.
24504853 How to select the right cost-effectiveness model? : A systematic review and stepwise appro 2014 May OBJECTIVE: In the current study, we propose an approach for selection of a model that is transferable to a specific decision-making context (in this case, the Netherlands), using the case of rheumatoid arthritis (RA). The objectives of this study were (a) to perform a systematic literature review to identify existing health economic evaluation models for economic evaluation of disease-modifying antirheumatic drugs (DMARDs) in RA; and (b) to test the appropriateness of a stepwise model-selection process. METHODS: First, we searched Medline and Embase to identify relevant studies in the English language, published between 1 January 2002 and 31 August 2012. From the included studies, all unique models were identified. Second, we applied a multi-step approach to model selection. Models that did not meet all minimal methodological and structural requirements based on the Outcome Measures in Rheumatology (OMERACT) criteria were excluded. Next, models were assessed on the basis of their fit when transferred to the Dutch health care setting. The criteria for model fit were transferability factors, as published by Welte et al., after exclusion of those that were deemed transferable by simple adaptation. Finally, the remaining models underwent a general quality check using the Philips checklist. Models showing good fit and high quality were considered to be transferable to the Dutch health care setting, using simple adaptation. RESULTS: The systematic literature search identified 498 articles, which included 33 unique health economic evaluation models. Only six models passed the minimal methodological and structural requirements. Two of these models had an imperfect transferability fit to the Dutch health care setting, according to the Welte method. The remaining four models were, according to the Philips method, of good quality and were expected to be transferable by a simple adaptation. CONCLUSION: This study introduces a stepwise approach for selecting health economic evaluation models that are transferable by a simple adaptation. The approach seems feasible and can be applied in various therapeutic areas, provided that the minimal methodological and structural requirements are defined accordingly. Availability of health economic evaluation models coupled with structured model selection could improve the efficiency, quality and comparability of health economic research.
23768941 Genetics in rheumatoid arthritis beyond HLA genes: what meta-analyses have shown? 2013 Aug OBJECTIVE: Rheumatoid arthritis (RA) is a complex disorder with many genetic and environmental factors to account for disease susceptibility. Individual genetic association studies usually suffer from small sample size leading to biased results of polymorphisms association with RA liability. Therefore, meta-analyses seem to resolve this limitation, up to a point, increasing the power of statistical analyses. In this review, we summarize the current knowledge of non-HLA genetic factors contributing to RA predisposition based on meta-analyses. METHODS: Using the key words: rheumatoid arthritis, meta-analysis, and polymorphism, we searched the PubMed database for the associated articles. Up to the middle of November 2012, seventy-nine articles fulfilled the criteria and highlighted the current findings on the genetic factors contributing to RA susceptibility. RESULTS: The association with RA was confirmed for 32 gene polymorphisms, being population specific in some cases. However, meta-analyses did not confirm an association in case of 16 gene variants, previously studied in individual studies for their association with RA. CONCLUSIONS: The use of bioinformatics tools and functional studies of the summarized implicated genes in RA pathogenesis could shed light on the molecular pathways related to the disorder, helping to the development of new drug targets for a better treatment of RA.
24111422 Development of lifelog sharing system for rheumatoid arthritis patients using smartphone. 2013 In this paper, we report the development of a lifelog sharing system for rheumatoid arthritis patients. Our system can objectively assess patients' condition from day to day via their smartphone use. We conducted a field experiment to investigate the feasibility of lifelog collection and sharing. The rate of patient assessment is very high. The system collects daily change in patients' activity as influenced by the disease.
22618411 Major depressive disorder in patients with rheumatoid arthritis. 2013 Mar OBJECTIVE: To investigate the point prevalence of major depressive disorder (MDD) as diagnosed by the Mini-International Neuropsychiatric Interview (M.I.N.I) in patients with rheumatoid arthritis (RA) and to determine whether MDD is related to features of RA disease, such as disease activity or physical dysfunction. METHODS: Of the patients with RA who participated in the IORRA survey conducted in October 2005, 162 were evaluated using the M.I.N.I., the Center for Epidemiologic Studies-Depression (CES-D) scale, and the two-question depression screen for MDD. RA clinical features were obtained from the concomitant IORRA cohort database. Relationships between MDD and RA disease features were analyzed by the Wilcoxon rank sum test and Pearson's chi-square test. RESULTS: The point prevalence of MDD as diagnosed by the M.I.N.I. was 6.8 % in our Japanese patients with RA. The percentage of depressive patients was determined to be 23.5, 17.3, or 7.4 % according to the CES-D scale with cut-off points of 16, 19, or 27, respectively, and 14.2 % according to the two-question depression screen. The best cut-off point for CES-D for risk of MDD diagnosed by M.I.N.I. in this study was determined to be 23, with 11.7 % depressive patients having the highest sum of sensitivity and specificity. No relationship between MDD and RA disease activity was detected. CONCLUSION: By using the well-established structural interview instrument M.I.N.I., we determined the point prevalence of MDD in the RA patients enrolled in this study to be 6.8 %, leading to the conclusion that concomitant MDD does not seem to influence disease activity in RA patients.
24252037 Increased generation of pre-plasmacytoid dendritic cells in bone marrow of rheumatoid arth 2014 May OBJECTIVE: Plasmacytoid dendritic cells (pDCs) have been found to be accumulated in synovial tissues in rheumatoid arthritis (RA). Since pDCs originate from bone marrow (BM), we explored the differentiation of pDC in BM in RA and osteoarthritis (OA). METHODS: BM mononuclear cells (BMMNCs) of the posterior ileac crest from 25 RA patients and 22 OA patients were examined for the expression of BDCA2 and CD34 by flow cytometry. The degree of synovial proliferation was assessed on light microscopy in 10 of 25 RA patients. RESULTS: There were no significant differences in percentages of CD34 + cells or BDCA2 + cells within BMMNC between RA and OA. However, RA BMMNC contained higher percentages of BDCA2 + CD34 + cells (pre-pDCs) than OA BMMNCs. Accordingly, percentages of BDCA2 + CD34+ cells within BM CD34 + cells were significantly higher in RA than in OA. Finally, the percentages of BDCA2 + CD34+ cells within BM CD34 + cells were significantly correlated with the degree of synovial proliferation in RA. CONCLUSION: These results indicate that the generation of pre-pDC from BM CD34 + cells is increased in RA compared with OA. Moreover, the data suggest that the increased output of pDC from BM might be involved in the synovial proliferation in RA.
24891304 "Stiffness has different meanings, I think, to everyone": examining stiffness from the per 2014 Nov OBJECTIVE: Stiffness is a well-recognized symptom of rheumatoid arthritis (RA). It is frequently queried during clinic visits as an indicator of disease activity and was included in the 1961 and 1987 RA classification criteria. Little is known about how people with RA experience stiffness and its impact on their lives. METHODS: We conducted 4 focus groups including 20 people with RA (4-6 participants per group) from 1 academic clinical practice and 1 private practice to generate accounts of stiffness experiences. Qualitative inductive thematic data analysis was conducted. RESULTS: Five overarching themes were identified: relationship of stiffness with other symptoms, exacerbating or alleviating factors and self-management, stiffness timing and location, individual meanings of stiffness experiences, and impact of stiffness on daily life. CONCLUSION: Focus group discussions revealed individual stiffness experiences as diverse and complex. Several stiffness features were endorsed by a majority of participants, but few, if any, were universally experienced; thus, the significance of stiffness as an expression of the disease varied widely. Discussions yielded descriptions of how individual limits imposed by RA in general and stiffness in particular may change over time and were intertwined with adaptations to preserve participation in valued life activities. These results concerning the diversity of the stiffness experience, consequential adaptations, and its impact suggest that a more individualized approach to stiffness measurement may be needed to improve stiffness assessments.
24896630 Specific therapy to regulate inflammation in rheumatoid arthritis: molecular aspects. 2014 Rheumatoid arthritis (RA) is a chronic inflammatory disease in which persistent inflammation of synovial tissue results in a progressive functional decline of the joint and premature mortality. TNF inhibitors were the first biological disease-modifying antirheumatic drugs (DMARDs) used to treat RA. Since then, new biological drugs have emerged, such as inhibitors of IL-1, IL-6 and others, with different mechanisms of action that include the depletion of B cells and the inhibition of T-cell costimulation. Recently, RA treatments have incorporated the use of synthetic DMARDs. This review describes the molecular aspects of the mechanisms of action of biological and synthetic DMARDs, discusses the adverse effects and limitations of established therapies and analyses the alternative approaches to RA treatment.
23885620 [Effects of moxibustion on expression of hypothalamic POMC mRNA and PDYN mRNA in rats with 2013 May OBJECTIVE: To explore the central mechanism of moxibustion on analgesic effect. METHODS: Male Wistar rats were screened by pain threshold value before making model, and 48 rats whose pain threshold was (250 +/- 25) g were selected. Twelve male Wistar rats were randomly selected as a normal group. For the rest rats the rheumatoid arthritis (RA) model was duplicated by raising in a windy, cold and wet environment combined with injection of Freund's complete adjuvant (FCA), and then they were randomly divided into a model group, a moxibustion group and a moxa volatile oil group, 12 rats in each group. The moxibustion and the moxa volatile oil igroup were treated with moxibustion and moxa volatile oil at "Shenshu"(BL 23) and "Zusanli"(ST 36), respectively, for 15 days. No interventions were added on the model group and the normal group. The pain threshold in Iinjured foot and the expression of hypothalamic POMC mRNA and PDYN mRNA in rats were observed. RESULTS: Compared with the normal group, the pain threshold and the expression of hypothalamic POMC mRNA and PDYN mRNA in the model group were increased (all P < 0.01). Compared with the model group, the pain threshold and the expression of hypothalamic POMC mRNA and PDYN mRNA in the moxibustion group were increased significantly (all P < 0.01), but no statistically significance in the moxa volatile oil group (P > 0.05). Compared with the moxa volatile oil group, the above-mentioned observative indices in moxibustion group were all increased significantly (all P < 0.01). CONCLUSION: Moxibustion has obvious analgesic effect and its mechanism may be related to the increasing expression of hypothalamic POMC and PDYN mRNA through the warming effect of moxibustion.
22116525 Undifferentiated connective tissue disease in a rheumatology center in Cali, Colombia: cli 2013 Apr The aim of the study is to evaluate the clinical and serological features of patients with undifferentiated connective tissue disease (UCTD) of a rheumatology referral center in Cali, Colombia, who were followed for a year. A retrospective analysis of a cohort of patients with an initial diagnosis of UCTD and monitoring for at least 12 months was carried out. A total of 94 patients with UCTD (97.9% women) were evaluated, with an average follow-up of 51 ± 35.7 months. Only 13 patients (13.8%) evolved into a defined connective tissue disease (CTD), of which 8.5% (n:8) developed systemic lupus erythematosus (SLE), 4.2% (n:4) Sjögren syndrome (SS) and 1.1% (n:1) rheumatoid arthritis (RA). A mean period of 35.8 ± 29.2 months between UCTD diagnosis and definite develop of a CTD was found. Arthritis, Raynaud's phenomenon and photosensitivity were statistically significant (<0.001) for development of CTD. After a mean follow-up of 4.25 years, most of the patients with UCTD showed a favorable evolution. Arthritis, Raynaud's phenomenon and the presence of photosensitivity were predictors for the development of CTD. It requires a consensus to establish criteria for the classification of UCTD.
24670135 Weighting with the Lansbury articular index improves the correlation of ultrasound score w 2014 Nov OBJECTIVE: To determine whether weighting improves the correlation of ultrasound (US) score with serum matrix metalloproteinase-3 (MMP-3) level in rheumatoid arthritis (RA). METHODS: As ultrasound examination was performed on 100 RA patients, and the severity of synovial effusion and synovial hypertrophy and the blood flow were semi-quantitatively graded from 0 to 3 by using the gray-scale (GS) and power Doppler (PD) modes. We then calculated the sums of the scores of the 28 joints of each patient in the 2 modes, that is, the GS28 and PD28 scores, as well as the respective scores weighted using the Lansbury articular index (LAI, shoulder and elbow, × 12; wrist, × 8; and knee, × 24)-Lans GS28 and Lans PD28 scores. RESULT: The Lans PD28 score showed a higher correlation with MMP-3 (r = 0.591; 95% confidence interval, 0.446-0.705, p < 0.0001) than the existing measures. The scores of the large joints-the knee, shoulder, and elbow-correlated well with the serum MMP-3 level. CONCLUSION: Weighting with the LAI can improve the correlation of US findings with serum MMP-3 level. Bidirectional approach based on both serum MMP-3 level and US scores can further improve the assessment of disease activity in RA patients.
24692402 Associations of hydroxychloroquine use with lipid profiles in rheumatoid arthritis: pharma 2014 Nov OBJECTIVE: To evaluate the association of hydroxychloroquine (HCQ) use with lipid profiles in a Veterans Affairs Rheumatoid Arthritis (VARA) cohort. METHODS: Lipid profiles in HCQ users were compared with HCQ nonusers, adjusting for potential confounders (age, sex, race, disease activity, prednisone, disease-modifying antirheumatic drugs, diabetes mellitus, and statin use). Applying current National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines for reduction of cardiovascular disease (CVD) events risk, the frequency of target lipid profiles with HCQ status was evaluated. Varied periods of HCQ exposure were compared to ascertain pharmacologic associations with lipid values. CVDs were compared between HCQ users and nonusers. RESULTS: In an elderly, predominantly male VARA cohort, 1,011 patients had lipid profiles; 787 patients (77.8%) were white. Statin use was recorded in 11.6% of patients, diabetes mellitus in 33.5%, and CVD in 31.2%. HCQ users (n = 150) were older, had longer rheumatoid arthritis (RA) disease duration, and had lower disease activity. Optimum lipid profiles, including total cholesterol:high-density lipoprotein (HDL) and HDL:low-density lipoprotein ratios (P ≤ 0.001), were more frequent in HCQ users, with the exception of HDL (P = 0.165), and persisted in multivariate analyses. Similarly, more HCQ users had NCEP-ATP III target levels. Varied periods of HCQ exposure suggested lipid changes to occur early, but lost within a year of drug discontinuation. HCQ users had less prevalent CVD. CONCLUSION: In RA patients, HCQ use of at least 3 months' duration was associated with better lipid profiles irrespective of disease activity or statin use. Given the increased CVD risks in RA and the relative low cost and toxicity of HCQ, continued use, regardless of treatment regimen, should be considered.
23188554 A study of the link between bone turnover markers and bone mineral density with inflammati 2013 Mar In this study, the levels of bone turnover markers (BTMs) and bone mineral density (BMD) were studied in relation to body mass and several inflammatory markers, in postmenopausal patients with rheumatoid arthritis (RA). Fifty-nine postmenopausal women with active RA (lean, overweight, obese) were studied. The femoral BMD and serum levels of BTMs: osteocalcin (OC) and collagen type I cross-linked C-telopeptide fragments (CTX), and osteopontin (OPN), resistin, high sensitivity C-reactive protein, interleukin-6, tumor necrosis factor (TNF)-α in these patients were measured. It has been noticed that obese women had significantly higher total femoral BMD and total T-score compared to the lean subjects (p ≤ 0.01). The significant associations of BMD measures and CTX levels with body mass parameters (p ≤ 0.01 and p < 0.05, respectively) were found. Values of neck BMD adjusted for BMI were inversely associated with concentrations of TNF-α (p < 0.05). Osteocalcin levels inversely correlated with resistin (p ≤ 0.01) and CTX levels positively correlated with OPN (p ≤ 0.01). There were found no associations between BTMs and BMD with other inflammatory indices. Inverse correlations between OPN levels and body mass (p < 0.05), waist circumference (p < 0.05), and duration of postmenopausal period (p ≤ 0.01) were observed. Findings of the present study suggest that body mass and inflammatory markers, most of all OPN, resistin and TNF-α, play an important role in bone metabolism in postmenopausal women with active RA.
24760349 Bee venom acupuncture for rheumatoid arthritis: a systematic review protocol. 2014 Apr 23 INTRODUCTION: This systematic review aims to analyse the trial data on the effects of bee venom acupuncture (BVA) for rheumatoid arthritis (RA). METHODS AND ANALYSIS: The following 14 databases will be searched from their inception to March 2014: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), AMED, CINAHL, six Korean medical databases (OASIS, Korean Traditional Knowledge Portal, Korean Studies Information Service System, KoreaMed, Korean Medical Database and DBPIA) and three Chinese databases including CNKI (China National Knowledge Infrastructure), Wanfang and VIP. The methodological quality will be assessed using the Cochrane risk of bias tool. DISSEMINATION: The systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print. TRIAL REGISTRATION NUMBER: PROSPERO 2013: CRD42013005853.
24484294 Rheumatoid arthritis and genetic variations in cytokine genes: a population-based study in 2014 OBJECTIVE: The aim of our study was to determine the genetic associations between polymorphisms of the IL1β gene (-511C/T and +3953C/T) and IL6 gene (-174G/C) with disease susceptibility and severity in patients with rheumatoid arthritis (RA) in ethnic Kashmiri population. METHODS: Allele and genotype frequencies of IL1β -511 C/T, IL1β +3953 C/T and IL6 -174 G/C polymorphisms were compared between 150 RA patients and 200 healthy controls by using PCR-RFLP method. RESULTS: We did not find any significant association between IL1b +3953 C/T and IL6 -174 G/C polymorphism and Rheumatoid Arthritis risk (p>0.05), but IL1β +3953 CT genotype was associated significantly with increased SJC and ESR and IL6 -174 GG genotype was associated significantly with increased ESR. However IL1b -511C/T polymorphism was significantly associated with rheumatoid arthritis risk and the carriers of IL1β -511 'C' allele (CC and TC genotypes) appeared to have lower risk for RA development. CONCLUSION: Our findings suggest that the IL1b -511 'C' allele has a protective role from disease development. Furthermore our results suggest a possible role of IL1b +3953 CT and IL6 -174 GG genotypes as disease activity markers of rheumatoid arthritis.
24550173 The global burden of rheumatoid arthritis: estimates from the global burden of disease 201 2014 Jul OBJECTIVES: To estimate the global burden of rheumatoid arthritis (RA), as part of the Global Burden of Disease 2010 study of 291 conditions and how the burden of RA compares with other conditions. METHODS: The optimum case definition of RA for the study was the American College of Rheumatology 1987 criteria. A series of systematic reviews were conducted to gather age-sex-specific epidemiological data for RA prevalence, incidence and mortality. Cause-specific mortality data were also included. Data were entered into DisMod-MR, a tool to pool available data, making use of study-level covariates to adjust for country, region and super-region random effects to estimate prevalence for every country and over time. The epidemiological data, in addition to disability weights, were used to calculate years of life lived with disability (YLDs). YLDs were added to the years of life lost due to premature mortality to estimate the overall burden (disability-adjusted life years (DALYs)) for RA for the years 1990, 2005 and 2010. RESULTS: The global prevalence of RA was 0.24% (95% CI 0.23% to 0.25%), with no discernible change from 1990 to 2010. DALYs increased from 3.3 million (M) (95% CI 2.6 M to 4.1 M) in 1990 to 4.8 M (95% CI 3.7 M to 6.1 M) in 2010. This increase was due to a growth in population and increase in aging. Globally, of the 291 conditions studied, RA was ranked as the 42nd highest contributor to global disability, just below malaria and just above iodine deficiency (measured in YLDs). CONCLUSIONS: RA continues to cause modest global disability, with severe consequences in the individuals affected.
22736097 A novel mouse model that develops spontaneous arthritis and is predisposed towards atheros 2013 Jan OBJECTIVES: Patients with rheumatoid arthritis (RA) have a reduced life expectancy due to increased cardiovascular disease. The lack of a suitable animal model resembling both RA and atherosclerosis has hindered studies demonstrating a direct link between systemic inflammation in RA and the development of atherosclerosis. Our objective was to overcome this barrier by generating an animal model (K/BxA(g7)) that spontaneously develops both RA-like disease and atherosclerosis. METHODS: Arthritis severity was evaluated using clinical indices and immunohistochemical staining of ankle joint specimens. Aortic atherosclerosis was delineated via Sudan IV staining and immunohistochemical analysis. Serum cholesterol and lipoprotein levels were measured using enzymatic assays. Serum levels of cytokines, chemokines and adipokines were determined by Luminex assays. RESULTS: K/BxA(g7) mice developed a destructive arthropathy followed by prominent aortic atherosclerosis. These animals also displayed dyslipidaemia, characterised by reduced serum levels of total cholesterol and high-density lipoprotein, and increased low-density lipoprotein (LDL)/vLDL compared with control mice. Further, there were higher levels of circulating inflammatory mediators, such as interleukin-6, sRANKL and CCL5 in atherosclerotic K/BxA(g7) mice compared with controls. Treatment with etanercept reduced arthritis and atherosclerosis development in K/BxA(g7) mice. CONCLUSIONS: K/BxA(g7) mice recapitulate the same sequence of events occurring in patients with RA, namely an erosive, inflammatory arthritis followed by atherosclerosis. These data suggest that the K/BxA(g7) mouse is a novel system for investigating the interplay between systemic inflammation occurring in RA and the development of atherosclerosis.