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ID PMID Title PublicationDate abstract
23215763 Bi(o)communications among peripheral blood fractions: a focus on NK and NKT cell biology i 2013 Jun Rheumatoid Arthritis (RA) is an autoimmune disease with unknown pathophysiology involving many interwoven signalling cascades. ROS, NK and NKT cells might be crucial in the disease severity of RA of which the role of NK and NKT cells are controversial in literature. However, the role of oxidative stress, its impact on NK and NKT cell immunobiology and disease activity (DAS28) is largely unknown. Therefore, we studied the role of oxidative stress and NK cell subsets in the pathogenesis of RA. The state of oxidative stress in various peripheral blood fractions, percentage NK and NKT cell expression, their altered apoptotic signaling pathways involving mitochondrial membrane potential, FAS associated death domain (FADD) mediated pathways and DNA damage were analyzed. Results indicated a state of profound oxidative stress in the peripheral blood of RA patients where percentage of NK and NKT cell subsets diminished while ROS levels increased. The depolarized mitochondrial membrane potential, FAS, FASL and active caspase-3 positive NK and NKT cell subsets were considerably elevated in patients. The DNA damage, assessed as percentage of DNA in comet tail, was significantly elevated. Findings of the present work indicate increased apoptosis of peripheral NK and NKT cells in the diseased condition. PBMC and RBC are the major sites of enhanced oxidative stress. The state of oxidative stress and altered immunobiology of NK and NKT cells strongly correlated with Disease activity score. The present study strongly supports the protective role of NK cell subsets in the pathogenesis of RA.
25305139 Inflammatory burden interacts with conventional cardiovascular risk factors for carotid pl 2015 May OBJECTIVE: Patients with RA have an increased risk of atherosclerosis and cardiovascular (CV) diseases compared with the general population. The aim of this study was to evaluate the role of inflammatory burden in the formation of carotid plaques in patients with RA. METHODS: We performed carotid artery US to measure the carotid intima-media thickness (IMT) and plaques in 406 patients with RA and 209 age- and sex-matched healthy controls. To assess the inflammatory burden, the area under the curve (AUC) of ESR over time was calculated. RESULTS: The carotid plaque frequency and mean IMT were significantly increased in patients with RA relative to controls. After adjustment for age and gender, the presence of carotid plaques in patients with RA was associated with HAQ score, tender joint count (TJC), swollen joint count (SJC), 28-joint DAS, ESR, CRP, LEF use, current corticosteroid dose and the number of conventional CV risk factors. After multivariate regression analysis, the factors significantly associated with plaque formation were TJC (P = 0.002), ESR (P = 0.002) and the number of conventional CV risk factors (P = 0.041). Among 194 RA patients with ESR AUC data, the presence of carotid plaque was independently associated with both the ESR AUC and number of conventional CV risk factors, which showed a synergistic interaction. CONCLUSION: Cumulative inflammatory burden contributes to the development of carotid atherosclerosis through a synergistic interaction with conventional CV risk factors in patients with RA.
24924607 25-Hydroxy vitamin D and its relationship with clinical and laboratory parameters in patie 2015 Feb The objective of this study is to evaluate the prevalence of vitamin D insufficiency in patients with rheumatoid arthritis (RA) and its association with disease activity, severity and physical disability. We included patients with rheumatoid arthritis followed in Rheumatology Department of Hassan II University Hospital, Fez, Morocco. Patients suffering from liver and kidney insufficiency and those who had received vitamin D in the previous 12 months have been excluded. Statistical analysis was done using SPSS v 18. A bivariate analysis and logistic regression were used to identify factors associated with vitamin D deficiency. One hundred seventy patients were included with a mean age of 50 ± 12.1 [17-83] years, and a female predominance (88.1%). All of our patients had hypovitaminosis D. The prevalence of 25(OH)-D insufficiency and deficiency was 64.5 and 35.5% successively. In unadjusted analysis, vitamin D concentration was inversely associated with pain visual analog scale VAS score (p < 0.001), asthenia VAS (p < 0.001), morning stiffness (p = 0.03), number of tender joints (p = 0.004), number of swollen joints (p < 0.001), inflammatory markers (p = 0,012), Disease Activity Score (p = 0.009), physical disability using Health Assessment Questionnaire (HAQ) (p = 0.001), and severity of the disease (p < 0.001). After logistic regression persisted association with female sex (OR = 4.3, CI = [0.94 to 20.976], p = 0.05), asthenia VAS (OR = 1.029, CI = [1.011 to 1.046], p = 0.001), and with the severity of the disease (OR = 2.910, CI = [1.314-6.441], p = 0.008). The vitamin D deficiency is common in our patients with RA. This deficiency is associated with female sex, severe asthenia, and the severity of the disease.
22986289 Traditional cardiovascular risk factors, inflammation and cardiovascular risk in rheumatoi 2013 Jan Multiple studies demonstrate an increased cardiovascular (CV) risk associated with RA compared with the general population. While part of this risk appears to be mediated by RA-specific factors, such as long-term inflammation, traditional CV comorbidities also play an important role. We review evidence from previous studies of the relationship between RA and traditional CV comorbidities such as dyslipidaemia, obesity, insulin resistance and diabetes, hypertension, cigarette smoking and physical inactivity. We examine the prevalence and consider the effect of inflammation and RA treatments on these risk factors. Finally, we discuss three widely used CV risk estimators, the Framingham Risk Score, Reynolds Risk Score and the Systematic Coronary Risk Evaluation, and their performance in patients with RA. The traditional CV risk factors that appear to differ significantly between RA cases and controls include insulin resistance, abnormal fat distribution, cigarette smoking and lack of physical activity. Dyslipidaemia, diabetes and hypertension may also be elevated in RA; however, the evidence is conflicting. Overall, we found that the majority of information regarding CV risk factors in RA stems from data collected as covariates for studies on CV disease. A gap in knowledge exists regarding detailed information on individual risk factors in RA, their prevalence and modifications that occur as a result of inflammation or treatment. More studies are needed to develop methods for accurate CV risk estimation in RA.
24665115 The autoimmune-associated genetic variant PTPN22 R620W enhances neutrophil activation and 2015 Aug OBJECTIVES: A genetic variant of the leukocyte phosphatase PTPN22 (R620W) is strongly associated with autoimmune diseases including rheumatoid arthritis (RA). Functional studies on the variant have focussed on lymphocytes, but it is most highly expressed in neutrophils. We have investigated the effects of the variant on neutrophil function in health and in patients with RA. METHODS: Healthy individuals and patients with RA were genotyped for PTPN22 (R620W) and neutrophils isolated from peripheral blood. Neutrophil adhesion and migration across inflamed endothelium were measured. Calcium (Ca(2+)) release and reactive oxygen species (ROS) production in response to fMLP stimulation were also assessed. RESULTS: Expression of R620W enhanced neutrophil migration through cytokine activated endothelium (non-R620W=24%, R620W=45% migrating cells, p<0.001). Following fMLP stimulation, neutrophils that were heterozygous and homozygous for R620W released significantly more Ca(2+) when compared to non-R620W neutrophils, in healthy individuals and patients with RA. fMLP stimulation, after TNF-α priming, provoked more ROS from neutrophils heterozygous for R620W in patients with RA (non-R620W vs R620W=∼1.75-fold increase) and healthy individuals (non-R620W vs R620W=fourfold increase) and this increase was statistically significant in healthy individuals (p<0.001) but not in patients with RA (p<0.25). CONCLUSIONS: Expression of PTPN22 (R620W) enhanced neutrophil effector functions in health and RA, with migration, Ca(2+) release and production of ROS increased. Neutrophils are found in large numbers in the RA joint, and this hyperactivity of R620W cells may directly contribute to the joint damage, as well as to the initiation and perpetuation of the chronic immune-mediated inflammatory processes driving the disease.
23671588 Neutrophils are essential as a source of IL-17 in the effector phase of arthritis. 2013 OBJECTIVE: Th17 has been shown to have a pivotal role in the development of arthritis. However, the role of IL-17 in the T cell-independent effector phase has not fully been examined. We investigated whether IL-17 is involved in the effector phase of arthritis by using K/BxN serum-induced arthritis model. METHODS: K/BxN serum was transferred into IL-17 knockout (KO) mice, SCID mice and their control mice, and arthritis was evaluated over time. In order to clarify the source of IL-17 in the effector phase, neutrophils or CD4+ T cells collected from IL-17 KO or control mice were injected into IL-17 KO recipient mice together with K/BxN serum. To examine if neutrophils secrete IL-17 upon stimulation, neutrophils were stimulated with immune complex in vitro and IL-17 in the supernatant was measured by ELISA. RESULTS: K/BxN serum-induced arthritis was much less severe in IL-17 KO mice than in WT mice. Since K/BxN serum-transferred SCID mice developed severe arthritis with high serum IL-17 concentration, we speculated neutrophils are the responsible player as an IL-17 source. When wild type (WT) but not IL-17 KO neutrophils were co-injected with K/BxN serum into IL-17 KO mice, arthritis was exacerbated, whereas co-injection of WT CD4+ T cells had no effect. In vitro, stimulation of neutrophils with immune complex caused IL-17 secretion. CONCLUSIONS: Neutrophils are essential as a source of IL-17 in the effector phase of arthritis. The trigger of secreting IL-17 from neutrophils may be immune complex.
25438197 Treatment of moderate rheumatoid arthritis with different strategies in a health resource- 2015 Jan OBJECTIVES: This paper aims to explore the cost-effectiveness of reduced doses or discontinuation of etanercept biosimilar (Yisaipu) in patients with moderately active rheumatoid arthritis (RA). METHODS: A discrete event simulation model was developed to project lifetime medical costs and quality-adjusted life-years (QALYs) in moderately active RA. Strategies starting with Yisaipu 50 mg/week for nine months following Yisaipu 50 mg/week, 25 mg/week or MTX maintenance were compared. Resource consumptions related to RA were estimated from the perspective of the Chinese health care system. An endpoint of the American College of Rheumatology (ACR) response was used to estimate the utility scores. Uncertainty in model parameters was analysed by sensitivity analyses. RESULTS: When using ACR as an endpoint for determining successful treatment, strategies starting with Yisaipu 50 mg/week for nine months following Yisaipu 50 mg/week or 25 mg/week maintenance showed the greatest number of QALYs gained (nearly 11.9 and 11.3 with or without rituximab after the failure of Yisaipu, respectively). If decision makers use a threshold of 3×the per capita GDP of China or Shanghai City in 2012, then the strategies most likely to be cost-effective are initial treatment with Yisaipu 50 mg/week for nine months following MTX maintenance and Yisaipu 25 mg/week maintenance, respectively. Results were sensitive to the cost of Yisaipu. CONCLUSIONS: The analysis indicates that, in China, replacing branded etanercept with Yisaipu is likely to be a cost-effective strategy in patients with moderately active RA.
24123677 A novel disease-modifying antirheumatic drug, iguratimod, ameliorates murine arthritis by 2013 Nov 15 Iguratimod, a novel disease-modifying antirheumatic drug, which is now used in clinics in China and Japan, has been confirmed as a highly efficacious and safe drug for rheumatoid arthritis therapy. The antiarthritic mechanism of iguratimod, especially compared with that of the classical disease-modifying antirheumatic drugs, has not been elucidated. In this study, we conducted a comparative analysis of the antiarthritic effects of iguratimod and two reference drugs, methotrexate and leflunomide. We found that iguratimod dose dependently and potently inhibited arthritic inflammation of the synovium in collagen-induced arthritis and predominantly targeted IL-17 signaling. Consistent with its effects in vivo, iguratimod significantly suppressed the expression of various proinflammatory factors triggered by IL-17 in the cultured fibroblast-like synoviocytes. The inhibition of IL-17 signaling by iguratimod was further linked to a decrease in the mRNA stability of related genes and a reduction in phosphorylation of MAPKs. Iguratimod mainly targets Act1 to disrupt the interaction between Act1 and TRAF5 and IKKi in the IL-17 pathway of synoviocytes. Together, our results suggest that iguratimod yields a strong improvement in arthritis via its unique suppression of IL-17 signaling in fibroblast-like synoviocytes. This feature of iguratimod is different from those of methotrexate and leflunomide. This study may be helpful for further understanding the unique antiarthritic mechanism of iguratimod in patients with rheumatoid arthritis.
23873875 Evaluation of myocardial function in patients with rheumatoid arthritis using strain imagi 2014 Oct OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD), although strategies to detect subclinical CVD are poorly characterised. The purpose of this study was to assess myocardial function by speckle-tracking echocardiography strain imaging in patients with RA without known CVD. METHODS: Eighty-seven patients with RA selected from a population-based sample underwent echocardiography. Left ventricular (LV) and right ventricular (RV) longitudinal peak systolic strain were measured. A subset of 59 patients with RA was compared with 59 age-, gender- and race-matched subjects with normal echocardiography and no CVD or risk factors. RESULTS: The mean ± SD age of the patients with RA and the normal patients was 55.7±12.1 and 54.5±12.2 years (p=0.42), respectively, with 45 (76%) women in each group. Global LV strain (-15.7±3.2% vs -18.1±2.4%, p<0.001) and RV strain (-17.9±4.7% vs -20.7±2.4%, p<0.001) was reduced in patients with RA compared with normal patients. Among all 87 patients with RA the mean disease duration and C-reactive protein at echocardiography were 10.0±6.1 years and 3.5±3.7 mg/L, and 74% were seropositive. Adjusted univariate regression analysis demonstrated a significant correlation between global LV strain and RA Health Assessment Questionnaire disability index (p=0.032), and borderline associations with prior use of oral corticosteroids (p=0.062) and methotrexate (p=0.054) after adjustment for age, gender, blood pressure, body mass index, heart rate and LV mass index. CONCLUSIONS: Global longitudinal LV and RV strain is reduced in patients with RA compared with healthy patients. Strain abnormalities correlate with RA disease severity. Strain imaging by echocardiography may detect early myocardial dysfunction in RA.
25274891 Coronary and abdominal aorta calcification in rheumatoid arthritis: relationships with tra 2014 Nov OBJECTIVE: To assess the influence of traditional cardiovascular (CV) risk factors, disease characteristics, and concomitant treatments in patients with rheumatoid arthritis (RA) on coronary artery calcification (CAC) and abdominal aorta calcification (AAC). METHODS: In our cross-sectional study, 75 patients with RA were compared with 75 age-matched and sex-matched control participants. The CAC and AAC scores were measured by computed tomography in patients with no clinical evidence of coronary artery disease. The relationships between the presence or absence of CAC and AAC and traditional CV risk factors, disease characteristics, and concomitant treatments in patients with RA were assessed in a multiple logistic regression analysis. RESULTS: The RA and control groups did not differ significantly in terms of age, sex composition, or the prevalence of traditional CV risk factors. AAC and CAC were more prevalent and severe in patients with RA than in controls. Older age (OR=1.15, p<0.01) and hypertension (OR=3.77, p=0.04) were found to be independently associated with CAC, whereas current use of methotrexate (MTX; OR=0.12, p=0.01) was found to be associated with the absence of CAC. Older age (OR per yr=1.17, p<0.001) and erosive arthritis (OR=3.78, p=0.03) were found to be independently associated with AAC. CONCLUSION: Our study demonstrates that in patients with RA, (1) CAC and AAC are more prevalent and more severe compared with age-matched and sex-matched control participants, (2) current use of MTX is a major determinant of the absence of CAC, and (3) erosive arthritis is a major determinant of AAC.
24023009 Depressive symptoms and rheumatoid arthritis: spouse empathic responding as a buffer. 2014 Apr OBJECTIVE: To examine the effects of depressive symptoms and spouse empathic responding on patient disability and marital quality over time and to identify factors that contribute to patients perceiving their spouses as responding empathically to their rheumatoid arthritis (RA). METHODS: Patients diagnosed with RA and their spouses (n = 133 couples) independently completed mailed questionnaires at baseline and 1 year later. Patients completed measures of functional impairment, marital quality, depressive symptoms, and perceived empathic responding from their spouse. Spouses reported their own depressive symptoms and empathic responding behavior. RESULTS: Perceived empathic responding was found to interact with spouse depressive symptoms, contributing significantly to the prediction of patient functional impairment at followup. Only when spouse empathic responding was low was spouse depression associated with greater patient functional impairment 1 year later. Similarly, in the model predicting patient marital quality at followup, there were significant 2-way interactions between perceived empathic responding and both spouse depressive symptoms and patient depressive symptoms. Only when spouse empathic responding was low did patient or spouse depression significantly predict poorer marital quality at followup. Patient perceptions of spouse empathic responding were found to depend on spouse reports of their own empathic responding, patient marital satisfaction, and the interaction of patient depressive symptoms and marital satisfaction. CONCLUSION: Empathic responding from the spouse was found to buffer against the negative effects of spouse depression on functional and marital outcomes for patients with RA. In developing couple-oriented RA treatments, increasing perceived empathic responding could serve as a useful target for intervention.
25146406 [The clinical electrophysiology and pathological characteristics of 15 cases of vasculitic 2014 May OBJECTIVE: To summarize the clinical features, electrophysiology and neuropathological characteristics of peripheral nerves in patients with vasculitic neuropathy. METHODS: We retrospectively analyzed the clinical, electrophysiology and neuropathological characteristics of 15 patients with vasculitic neuropathy who underwent electrophysiology and sural nerve biopsy in our department from January 2009 to June 2013. RESULTS: There were 8 males and 7 females, aged from 38 to 82 years old, with a peripheral neuropathy course ranged from 0.5 month to 60 months. In the total of 15 patients, 3 patients were diagnosed as nonsystemic vasculitic neuropathy, while the other 12 patients were diagnosed as systemic vasculitis neuropathy (SVN) including 5 cases of primary systemic vasculitis and 7 cases of secondary systemic vasculitis. In patients diagnosed as primary systemic vasculitis, there were 2 cases of Churg-Strass syndrome (CSS) and 3 cases of ANCA associated vasculitis. In patients diagnosed as secondary systemic vasculitis, there were 1 case of systemic lupus erythematosus (SLE), 2 cases of sicca syndrome (SS), 3 cases of rheumatoid arthritis (RA), 1 case of Behcet' s disease associated with thyroid papillary carcinoma, 1 case of hepatitis B and 1 case of RA-associated SS. For the pathological features of vasculitic neuropathy, type 1 lesion was found in 4 patients, type 2 lesion in 2 patients, and type 3 lesion in 9 patients. Axon degeneration was observed in 8 patients, while 7 patients manifested as axon degeneration associated with demyelination and local thickening of the perineurium was found in 2 patients. CONCLUSION: Multiple mononeuropathy and asymmetric polyneuropathy are the common clinical presentations of vasculitic neuropathy. Electrodiagnostic testing almost always reveals the evidence of a predominantly axonal and sensorimotor process with associated demyelination presented in some cases. Sural nerve biopsy shows changes indicative of an axonopathy.
24029290 [How to read a meta-analysis?]. 2014 Apr Meta-analysis is aimed at assessing an exhaustive, unbiased, reproducible, quantified and accurate synthesis of a research problem. It is sustained by a systematic review of the literature and has statistical particularities. Sources of error and bias are numerous. In this paper, we describe them following the methodology steps of a well-conducted meta-analysis. Causes of divergent conclusions of meta-analyses are described and illustrated with the example of cancer risk assessment in TNF inhibitor-treated rheumatoid arthritis patients. Eventually, this article provides key-points to help readers to detect sources of error and bias in meta-analyses.
22627098 Rituximab-induced hepatitis C virus reactivation in rheumatoid arthritis. 2013 Feb The B-cell depletion agent rituximab (RTX) is used in lymphoma and rheumatoid arthritis (RA), and there have been several case reports of an RTX-induced reactivation of hepatitis C virus in patients with lymphoma. However, there have been no papers detailing hepatitis C virus reactivation after RTX therapy in a patient with RA. Here we report a case of RTX-induced hepatitis C virus reactivation in a patient with RA. Physicians should be aware that a close follow-up of liver function and viral load is mandatory after RTX therapy in patients with RA and concomitant hepatitis C.
23504384 Osteonecrosis of the jaw and nonmalignant disease: is there an association with rheumatoid 2013 Jun OBJECTIVE: To review cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) occurring in association with benign disease and to describe and compare the clinical course and outcome for patients with BRONJ and rheumatoid arthritis (RA) or osteoporosis. METHODS: We retrospectively reviewed observations of all patients referred for treatment and followup for BRONJ from January 2007 to December 2011. Only patients with malignant disease were excluded. Demographic data, medical history, maxillofacial findings, BRONJ treatment, and followup were reviewed for each case. RESULTS: Over a 5-year period, we diagnosed 112 patients with BRONJ. Among these patients, 15 received bisphosphonate (BP) treatment for nonmalignant disease (mean age 65.7 ± 19.8 yrs, 80% women). Patients received BP for a variety of reasons: 8 (53%) to prevent osteoporosis in association with underlying RA; 6 (40%) to prevent idiopathic osteoporosis; and 1 (7%) to treat ankle algodystrophy. The mean oral BP exposure period was 48.4 months (median 36 mo). In 13 cases (86.6%), BRONJ was diagnosed following dental extraction. Of the 8 patients with RA, 5 (62.5%) were taking prednisone at the time of the discovery of BRONJ. Major surgery, sequestrectomy, or alveolectomy was performed in 9 patients (60%), all of whom healed within 3 to 36 months (mean 11.5 mo). Comparative analysis of all the variables showed no statistically significant differences between patients with RA and others. CONCLUSION: ONJ is a rare adverse effect of BP therapy, especially when administered orally. Within the limits of our study, we were unable to demonstrate a difference in BRONJ disease spectrum, clinical course, or outcome between patients with and those without RA.
25211401 Efficacy and safety of abatacept for patients with Sjögren's syndrome associated with rhe 2015 Mar Abstract Objective. To assess the efficacy and safety of abatacept for secondary Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). Methods. The primary endpoint of this 1-year, open-labeled, prospective, observational multicenter study of RA-associated secondary SS was the rate of SDAI remission at 52 weeks after initiation of abatacept therapy. The secondary endpoints included that of Saxson's test and Schirmer's test. Adverse events during the study period were also analyzed. Results. Thirty-two patients (all females) were enrolled in this study. Interim analysis at 24 weeks included assessment of efficacy (n = 31) and safety (n = 32). The mean SDAI decreased from 19.8 ± 11.0 (± SD) at baseline to 9.9 ± 9.9 at 24 weeks (P < 0.05). Patients with clinical remission, as assessed by SDAI, increased from 0 patient (0 week) to 8 patients (25.8%) at 24 weeks. Saliva volume (assessed by Saxson's test) increased slightly from 2232 ± 1908 (0 week) to 2424 ± 2004 (24 weeks) mg/2 min (n = 29). In 11 patients with Greenspan grading 1/2 of labial salivary glands biopsy, saliva volume increased from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min (P < 0.05). Schirmer's test for tear volume showed increase from 3.6 ± 4.6 (0 week) to 5.5 ± 7.1 (24 weeks) mm/5 min (n = 25; P < 0.05). Five adverse events occurred in five of 32 patients (15.6%), and three of these events were infections. Conclusion. Abatacept seems to be effective for both RA and RA-related secondary SS.
23335080 Tumor necrosis factor α induces sustained signaling and a prolonged and unremitting infla 2013 Apr OBJECTIVE: The nonresolving character of synovial inflammation in rheumatoid arthritis (RA) is a conundrum. To identify the contribution of fibroblast-like synoviocytes (FLS) to the perpetuation of synovitis, we investigated the molecular mechanisms that govern the tumor necrosis factor α (TNFα)-driven inflammatory program in human FLS. METHODS: FLS obtained from the synovial tissues of patients with RA or osteoarthritis were stimulated with TNFα and assayed for gene expression and cytokine production by real-time quantitative reverse transcription-polymerase chain reaction analysis and enzyme-linked immunosorbent assay. NF-κB signaling was evaluated by Western blotting. Histone acetylation, chromatin accessibility, and NF-κB p65 and RNA polymerase II (Pol II) occupancy at the interleukin-6 (IL-6) promoter were measured by chromatin immunoprecipitation and restriction enzyme accessibility assays. RESULTS: In FLS, TNFα induced prolonged transcription of messenger RNA (mRNA) for IL-6 and progressive accumulation of IL-6 protein over 4 days. Similarly, induction of mRNA for CXCL8/IL-8, CCL5/RANTES, matrix metalloproteinase 1 (MMP-1), and MMP-3 after TNFα stimulation was sustained for several days. This contrasted with the macrophage response to TNFα, which characteristically involved a transient increase in the expression of proinflammatory genes. In FLS, TNFα induced prolonged activation of NF-κB signaling and sustained transcriptional activity, as indicated by increased histone acetylation, chromatin accessibility, and p65 and Pol II occupancy at the IL-6 promoter. Furthermore, FLS expressed low levels of the feedback inhibitors A20-binding inhibitor of NF-κB activation 3 (ABIN-3), IL-1 receptor-associated kinase M (IRAK-M), suppressor of cytokine signaling 3 (SOCS-3), and activating transcription factor 3 (ATF-3), which terminate inflammatory responses in macrophages. CONCLUSION: TNFα signaling is not effectively terminated in FLS, which leads to an uncontrolled inflammatory response. The results suggest that prolonged and sustained inflammatory responses by FLS in response to synovial TNFα contribute to the persistence of synovial inflammation in RA.
23727459 Osteoimmunology: the study of the relationship between the immune system and bone tissue. 2013 Sep Bone tissue is a highly regulated structure, which plays an essential role in various physiological functions. Through autocrine and paracrine mechanisms, bone tissue is involved in hematopoiesis, influencing the fate of hematopoietic stem cells. There are a number of molecules shared by bone cells and immune system cells indicating that there are multiple connections between the immune system and bone tissue. In order to pool all the knowledge concerning both systems, a new discipline known under the term «osteoimmunology» has been developed. Their progress in recent years has been exponential and allowed us to connect and increase our knowledge in areas not seemingly related such as rheumatoid erosion, postmenopausal osteoporosis, bone metastases or periodontal disease. In this review, we have tried to summarize the most important advances that have occurred in the last decade, especially in those areas of interest related to rheumatology.
25381978 Insights on the role of physical activity in patients with rheumatoid arthritis. 2014 Nov Patients with rheumatoid arthritis (RA) are physically inactive, and trials have been undertaken to examine the effect of physical activity on pain, disease activity, functional ability and quality of life (QoL) in RA. The aim of this study was to explore the relationship between physical activity and disease-activity in RA and in healthy controls. Our findings showed that fewer RA patients had a professional occupation compared with controls, but patients and controls were similar with respect to the sedentary extent of their job. Physical exercise was inversely associated with disease activity (DAS-28), stiffness visual analog scale (VAS), patient global VAS and SF-36, but not associated with Health Assessment Questionnaire (HAQ), pain VAS, fatigue VAS, global health and the Arthritis Ipact Measurement Scale (AIMS), suggesting that pain and fatigue are important barriers to physical activity. Our findings suggest that this is more pronounced in RA patients who do not participate in regular physical activity, and so physical exercise should be recommended as part of comprehensive RA care.
24682293 Assessment of the treat-to-target strategy in patients with refractory rheumatoid arthriti 2014 Oct AIM: The goal of the present study was to prospectively assess the long-term clinical outcome of biologic modifying drug therapy in a population of Saudi rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: This is the first prospective, long-term report on the efficacy and safety of biologic therapy in Saudi RA patients. It is a single center, observational study with a follow-up period of 3 years. Enrolled were 120 biologic naïve patients (94 women, 78.3 %; mean age 48.4 ± 17.9 years, mean disease duration 7.3 ± 3.9 years) with the diagnosis of RA (ACR/EULAR, 2010 criteria) who were inadequate responders to methotrexate and synthetic DMARDs. RESULTS: After 3 years, the mean Disease Activity Index-28 (DAS-28), Health Assessment Questionnaire (HAQ), Pain Score, ESR, and CRP values improved significantly. Of the 99 patients completing the 3-year follow-up, 35.3 % of patients achieved DAS-28 remission and 53.5 % achieved low disease activity, and 11.1 % of patients had moderate to high activity scores. At the 3-year follow-up, 80 % of patients had no evidence of significant radiographic progression (achieved < 0.5 of the mean total Sharp score). Infections were reported in 11.7 % and significantly correlated with conjugate use of oral prednisolone at doses above 5 mg/day, with chest infections being the most common type of infection (6.7 %). CONCLUSION: The results of this study can be understood as real-life clinical experience displaying the incremental benefit of biologic therapy in refractory disease when it is added to other optimal strategies. The study showed satisfying clinical and functional benefit with considerable safety.