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ID PMID Title PublicationDate abstract
23225345 Crosscultural measurement equivalence of the Health Assessment Questionnaire II. 2013 Jun OBJECTIVE: To evaluate the crosscultural measurement equivalence of the US and Dutch Health Assessment Questionnaire II (HAQ-II) in rheumatoid arthritis (RA). METHODS: Item response theory (IRT) analyses were performed on US (n = 18,747) and Dutch (n = 1,022) HAQ-II data to evaluate the equivalence of crosscultural item performance. The observed inconsistencies were modeled by assigning country-specific item parameters to biased items. The impact of crosscultural item bias on the comparability of the Dutch and US total scores was analyzed by evaluating the agreement between physical function levels estimated from an IRT model with country-specific item parameters for biased items and physical function levels estimated from the original model that did not account for cultural bias. RESULTS: Two items showed significant crosscultural bias. However, the agreement in physical function estimates between the respecified and original models was very high, with an intraclass correlation coefficient >0.99 and Bland-Altman limits of agreement ranging from -0.08 to -0.01 on a latent scale with a mean of 0 and an SD of 1. CONCLUSION: This study suggests that the Dutch and US HAQ-II produce total scores that can be interpreted interchangeably across countries in RA studies, despite some minor bias at the item level.
24512606 In vivo kinematics of three-component mobile-bearing total ankle replacement in rheumatoid 2014 Nov OBJECTIVE: It is often that patients with rheumatoid arthritis (RA) who require ankle surgeries already have the degeneration of talocalcaneal joints. When talocalcaneal joint was fused, whether operatively or spontaneously, ankle kinematics would be affected. The purpose of this paper was to study in vivo kinematics of mobile-bearing total ankle replacement (TAR) in rheumatoid ankle with concomitant talocalcaneal arthrodesis or with preexisting spontaneous talocalcaneal fusion. METHODS: Thirteen TARs in ten patients with RA, in whom talocalcaneal joints had already been fused spontaneously or surgically, were studied. Fluoroscopic images were obtained while each patient was walking with full weightbearing on the implanted ankle. Thereafter tibio-talar motion was analyzed by 2D/3D registration technique. RESULTS: Average tibio-talar motion was 4.0 ± 5.3° for plantarflexion and 6.6 ± 0.3° for dorsiflexion. Average range of internal/external rotation, inversion/eversion and AP translation was 3.8 ± 1.3°, 2.7 ± 1.0° and 1.6 ± 0.6 mm, respectively. CONCLUSIONS: Mobility of mobile-bearing TAR with talocalcaneal fusion was small during the stance phase of gait, but clinically measured ROM was mostly preserved. The movements of internal/external rotation and AP translation were allowed to a certain degree, but not of inversion/eversion. Even though the movement of inversion/eversion is limited, talocalcaneal arthrodesis could be accompanied with mobile-bearing TAR in rheumatoid ankles.
24623460 In palindromic rheumatism, hand joint involvement and positive anti-CCP antibodies predict 2014 Jun This study aimed to determine the frequency of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies in a cohort of patients with palindromic rheumatism (PR) and to find determinants for progression to rheumatoid arthritis (RA). All new cases of PR (n=90) were included prospectively and followed up for 1 year, and a comparison group of RA cases (n=70) was also included. At study entry in all patients in both groups, RF and anti-CCP antibodies were tested, and the findings were compared and correlated. In the PR group at presentation, RF was positive in 30 patients (33.3%) and, in the RA group, in 45 patients (64.3%). Anti-CCP antibodies were positive in 35 patients (38.9%) with PR and in 58 patients (82.9%) with RA. In the PR group, positive correlations were observed between RF and C-reactive protein (CRP) (p=0.036), while anti-CCP positively correlated with disease duration (p=0.015) and CRP (p<0.001). At 1-year follow-up, 25 cases (27.5%) had progressed to RA, 3 (3.3%) cases had developed systemic lupus, 43 cases had responded to hydroxychloroquine with complete remission, five cases had developed other rheumatic diseases, and 14 cases had progressed to undifferentiated arthritis. After regression analysis, the involvement of hand joints and positive anti-CCP were the only predictors that determined progression into RA within a year (p<0.001 and p=0.02, respectively). Early hand joint involvement and positive anti-CCP at disease onset are good predictors for progression to RA in this domain.
25068448 Decreased circulating visfatin is associated with improved disease activity in early rheum 2014 OBJECTIVE: To evaluate circulating visfatin and its relationship with disease activity and serum lipids in patients with early, treatment-naïve rheumatoid arthritis (RA). METHODS: Serum visfatin was measured in 40 patients with early RA before and after three months of treatment and in 30 age- and sex-matched healthy individuals. Disease activity was assessed using the Disease Activity Score for 28 joints (DAS28) at baseline and at three and 12 months. Multivariate linear regression analysis was performed to evaluate whether improved disease activity is related to serum visfatin or a change in visfatin level. RESULTS: Serum visfatin was significantly elevated in early RA patients compared to healthy controls (1.92±1.17 vs. 1.36±0.93 ng/ml; p = 0.034) and significantly decreased after three months of treatment (to 0.99±0.67 ng/ml; p<0.001). Circulating visfatin and a change in visfatin level correlated with disease activity and improved disease activity over time, respectively. A decrease in visfatin after three months predicted a DAS28 improvement after 12 months. In addition, decreased serum visfatin was not associated with an improved atherogenic index but was associated with an increase in total cholesterol level. CONCLUSION: A short-term decrease in circulating visfatin may represent an independent predictor of long-term disease activity improvement in patients with early RA.
23507374 The physiologic increase in expression of some type I IFN-inducible genes during pregnancy 2013 Jun During pregnancy, most patients with rheumatoid arthritis (RA) experience a spontaneous improvement in their condition. Since type I interferons (IFN) have immunomodulatory properties, we investigated whether type I IFN-inducible genes are upregulated in pregnant patients with RA. Peripheral blood mononuclear cells were evaluated using quantitative real-time polymerase chain reaction for type I IFN-inducible genes (IFI 35, IFI44, IFI44L, IFIT3, OAS1, and Siglec1) in patients with RA and healthy women during and after pregnancy as well as in nonpregnant controls. IFN-alpha and IFN-beta levels in sera of patients and healthy donors were analyzed by enzyme linked immunosorbent assay. It was found that healthy women did not show a change of gene expression levels from the second trimester until postpartum, yet some type I IFN-inducible genes were significantly upregulated in pregnant and postpartum women compared with nonpregnant individuals. In patients with RA, a pronounced upregulation of IFI35 and IFI44 at the second trimester and a peak expression of Siglec1 at the third trimester were observed. Pregnancy levels of IFI35 and IFI44 in patients with RA were higher than those of nonpregnant patients with RA. No significant association of gene expression levels with disease activity was found. In the sera of patients and healthy women, IFN-beta was undetectable and IFN-alpha levels remained stable throughout pregnancy and postpartum. Thus, pregnancy can give rise to an increased expression of type I IFN-inducible genes, reflecting an upregulation of the innate immune system. However, an association of type I IFN-inducible genes with pregnancy induced disease amelioration seems unlikely.
22700248 Scientific basis of botanical medicine as alternative remedies for rheumatoid arthritis. 2013 Jun Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder that causes permanent disability and mortality to approximately 1 to 100 people in the world. Patients with RA not only suffer from pain, stiffness, swelling, and loss of function in their joints, but also have a higher risk of cardiovascular disease and lymphoma. Typically prescribed medications, including pain-relieving drugs, nonsteroidal anti-inflammatory drugs (NSAID), and disease-modifying antirheumatic drugs, can help to relieve pain, reduce inflammation and slow the course of disease progression in RA patients. However, the general effectiveness of the drugs has been far from satisfactory. Other therapeutic modalities like TNF-alpha (TNF-α) inhibitors and interleukin-1 receptor antagonists targeting precise pathways within the immune system are expensive and may be associated with serious side effects. Recently, botanical medicines have become popular as alternative remedies as they are believed to be efficacious, safe and have over a thousand years experience in treating patients. In this review, we will summarize recent evidence for pharmacological effects of herbs including Black cohosh, Angelica sinensis, Licorice, Tripterygium wilfordii, Centella asiatica, and Urtica dioica. Scientific research has demonstrated that these herbs have strong anti-inflammatory and anti-arthritic effects. A wide range of phytochemicals including phenolic acids, phenylpropanoid ester, triterpene glycosides, phthalide, flavonoids, triterpenoid saponin, diterpene and triterpene have been isolated and demonstrated to be responsible for the biological effects of the herbs. Understanding the mechanisms of action of the herbs may provide new treatment opportunities for RA patients.
23493630 Interleukin-6 receptor blockade selectively reduces IL-21 production by CD4 T cells and Ig 2013 Interleukin-6 (IL-6) levels are known to be increased in patients with rheumatoid arthritis (RA). Tocilizumab, a monoclonal antibody to the IL-6 receptor (IL-6R), reduces disease activity in RA, although its mechanisms of action remain unclear. Since IL-6 regulates cytokine production by CD4 T cells during activation, we investigated whether treatment with tocilizumab altered the phenotype and cytokine production by CD4 T cells in patients with rheumatoid arthritis. We show here that tocilizumab treatment does not change the production of cytokines by naïve CD4 T cells. However, tocilizumab treatment causes a selective decrease of IL-21 production by memory/activated CD4 T cells. Since IL-21 is known to promote plasma cell differentiation, we examined the effect of tocilizumab on the production of autoantibodies. We show that there is a decrease in the levels of IgG4 anti-CCP antibodies, but there is no effect on IgG1 anti-CCP antibodies. In addition, we show that IL-21 is a powerful inducer of IgG4 production by B cells. Thus, IL-6 contributes to the presence of IgG4-specific anti-CCP autoantibodies in RA patients, likely through its effect on IL-21 production by CD4 T cells, and IL-6R blockade down-regulates this pathway.
24751698 Premature immunosenescence is associated with memory dysfunction in rheumatoid arthritis. 2015 BACKGROUND: Rheumatoid arthritis (RA) has been associated with premature immunosenescence and an increased prevalence of age-related morbidities including poor cognitive function. OBJECTIVE: We explored the relationships among lymphocyte subsets and memory in RA. METHODS: Thirty patients with RA and 19 age-matched healthy controls took part in this study. Cognitive function stress and depression scores were evaluated by structured clinical questionnaires. Lymphocytes were isolated and immunophenotyped by flow cytometry to investigate the following subsets: B cells, activated and naïve/memory T cells, regulatory FoxP3+ T (Treg) cells, Th17+ cells, NK cells and senescence-associated CD28- T cells. RESULTS: RA patients were more depressed than controls, but stress levels were similar in the 2 groups. Patients had impaired memory performance compared to controls, demonstrated by lower Mini-Mental State Examination scores and logical and working memories (all p < 0.0001). These group effects remained significant after correcting for depression and age. Patients had expansion of regulatory T cells, naïve CD4+ T cells and CD8+CD28- cells but reduced percentages of B cells and memory CD8+CD45RO+ T cells compared to controls. CD8+CD28- and CD8+CD45RO+ T cells were found to be negatively associated with memory. CONCLUSION: RA patients had reduced memory performance compared to healthy controls. Expansion of activated and senescence-associated T cells was correlated with poor memory performance.
23690656 Serum matrix metalloproteinase-3 in comparison with acute phase proteins as a marker of di 2013 Matrix metalloproteinase-3 (MMP-3) is involved in the immunopathogenesis of rheumatoid arthritis (RA), but little is known about its relationship to genetic susceptibility and biomarkers of disease activity, especially acute phase reactants in early RA. MMP-3 was measured by ELISA in serum samples of 128 disease-modifying, drug-naïve patients and analysed in relation to shared epitope genotype, a range of circulating chemokines/cytokines, acute phase reactants, autoantibodies, cartilage oligomeric protein (COMP), and the simplified disease activity index (SDAI). MMP-3 was elevated >1.86 ng/ml in 56.25% of patients (P < 0.0001), correlated with several biomarkers, notably IL-8, IL-6, IFN γ , VEGF and COMP (r values = 0.22-0.33, P < 0.014-0.0001) and with CRP and SAA levels (r = 0.40 and 0.41, resp., P < 0.0000) and SDAI (r = 0.29, P < 0.0001), but not with erosions or nodulosis. However, the correlations of CRP and SAA with SDAI were stronger (respective values of 0.63 and 0.54, P < 0.001 for both). COMP correlated with smoking, RF, and MMP-3. MMP-3 is significantly associated with disease activity, inflammatory mediators and cartilage breakdown, making it a potential biomarker of disease severity, but seemingly less useful than CRP and SAA as a biomarker of disease activity in early RA.
23129427 Association of TLR4 gene non-missense single nucleotide polymorphisms with rheumatoid arth 2013 May Toll-like receptor4 (TLR4) plays an important role in the induction and regulation of the innate or adaptive immune responses. Thus, the genetic variation in TLR4 gene may influence the development of autoimmune diseases such as rheumatoid arthritis (RA). Several studies have investigated the roles of genetic polymorphisms of TLR4 gene in RA, but most of these studies were restricted to two cosegregating functional missense polymorphisms Asp299Gly and Thr399Ile. To determine whether non-missense genetic polymorphisms located in regulatory region of TLR4 are related to RA in a Chinese Han population, four single nucleotide polymorphisms (SNPs) situated on 3' untranslating region (UTR) and 5' UTR were genotyped in 213 RA patients and 247 unrelated ethnically matched controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing techniques. Significant genetic associations were observed with the 3' UTR SNP rs41426344 and rs7873784. The minor allele C and homozygotic variant genotype CC of rs41426344 and minor allele C of rs7873784 were identified to be risk factors for the development of RA in Chinese Han people. Furthermore, by comparing the variation allele frequencies to other populations, prevalent genetic ethnic specificity was observed in all the four SNPs. Our study suggested that the effect of non-missense polymorphisms located in regulatory region would not be neglected in disease association analysis.
24290736 Is it possible to withdraw biologics from therapy in rheumatoid arthritis? 2013 Dec BACKGROUND: Biologic agents targeting tumor necrosis factor (TNF) have revolutionized the treatment of rheumatoid arthritis (RA). Clinical remission is perceived as a realistic primary goal, and its maintenance leads to structural and functional remission. OBJECTIVE: This study reviews whether discontinuation of biologic agents is possible after sustained remission and discusses its significance from the risk/benefit point of view (including safety and health economic considerations). METHODS: Using a strategic PubMed search, 45 original research articles regarding discontinuation of biologic agents were identified; 7 were selected that had an obvious focus on discontinuation of biologic agents. These articles included the TNF20, BeSt (Behandel Strategieen), and RRR (Remission Induction by Remicade in RA) studies. However, because of the limitations of the original search, we also review here some articles that did not focus mainly on discontinuation of biologic agents but that presented data regarding biologic-free control. These studies included OPTIMA (Optimal Protocol for Treatment Initiation With MTX and Adalimumab), PRESERVE, and CERTAIN, as well as some recent findings in the HONOR (Humira Discontinuation Without Functional and Radiographic Damage Progression Following Sustained Remission) study from our department. RESULTS: In BeSt and OPTIMA, clinical remission was sustained without functional progression by discontinuing TNF inhibitors, after reducing disease activity by using TNF inhibitors and methotrexate (MTX), in patients with early RA and who were MTX naive. In some studies (including RRR and HONOR), the discontinuation of TNF inhibitors after sustained remission was possible in some patients with long-standing RA who had an inadequate response to MTX. When disease activity flared up after treatment discontinuation, re-treatment with infliximab or adalimumab was highly effective and safe in the majority of patients. It is also clear that tight control with TNF inhibitors and MTX seems to be a prerequisite for having a better chance of biologic-free remission. CONCLUSIONS: Intensive treatment with TNF inhibitors may change the disease process of RA and potentially offers the possibility of a "treatment holiday" from biologic agents.
23383162 Blood monocyte chemotactic protein-1 (MCP-1) and adapted disease activity Score28-MCP-1: f 2013 OBJECTIVE: We assessed blood pentraxin 3 (PTX3) and macrophage chemotactic factor-1 (MCP-1) levels as indicators of disease activity in rheumatoid arthritis (RA) patients, because data on disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP) are still imperfect. METHODS: In 111 patients with RA, we examined longitudinal and cross-sectional correlations of blood PTX3, MCP-1, CRP, and ESR levels with measures of clinical arthritic activity, namely, swollen joint count (SJC), tender joint count (TJC), visual analog scale for general health (GH), DAS28, and adapted DAS28-MCP-1. RESULTS: Blood MCP-1, but not PTX3, was significantly correlated with SJC, TJC, DAS28, and DAS28-CRP. DAS28-MCP-1 was strongly correlated with DAS28 (r  = 0.984, P<0.001) and DAS28-CRP (r  = 0.971, P<0.001), and modestly correlated with CRP (r  = 0.350, P<0.001), and ESR (r  = 0.386, P<0.001). Similarly, the duration of arthritic symptoms, but not sex, was significantly correlated with variables of arthritic activity. In particular, DAS28-MCP-1 significantly correlated with DAS28 during a 6-month period (r  = 0.944, P<0.001; r  = 0.951, P<0.001; r  = 0.862, P<0.001; and r  = 0.865, P<0.001 for month 0, 1, 3, and 6, respectively). CONCLUSION: Blood MCP-1 and adapted DAS28-MCP-1, but not blood PTX3, may be useful in monitoring RA activity.
25086283 Clinical evaluation of a novel chemiluminescent immunoassay for the detection of anti-citr 2014 Nov 1 BACKGROUND: We evaluated the analytical and clinical performances of a novel, automated chemiluminescent immunoassay in comparison with several anti-citrullinated protein antibody (ACPA) assays (2nd and 3rd generations) based on various platforms and technologies. METHODS: Samples from rheumatoid arthritis (RA) patients (n=141) and controls (n=153) were collected based on an ordered ACPA test. All samples were tested with QUANTA Flash® CCP3, QUANTA Lite® CCP3, QUANTA Lite® CCP3.1, CCPlus and EliA® CCP assays. Rheumatoid factor (RF) was determined using Quantex RF(II). An additional cohort consisting of RA patients from three different sources (116, 79 and 50 samples), 61 juvenile idiopathic arthritis (JIA) patients and 233 controls were used in an extended evaluation on QUANTA Flash® CCP3 only. Precision and linearity of the QUANTA Flash® CCP3 were assessed according to CLSI guidelines. RESULTS: All ACPA assays showed good qualitative and quantitative agreements. The Quanta Flash CCP3 assay showed good analytical and clinical performance. Based on the extended cohort, the sensitivity, specificity and likelihood ratios of the novel Quanta Flash® CCP3 were defined as 70.2%, 97.4% and 27.3/0.31, respectively. CONCLUSION: Good agreements between different ACPA assays based on diverse platforms were found. Quanta Flash CCP3 is a reliable test for the fully automated and rapid detection of ACPA.
23607804 The effect of targeted rheumatoid arthritis therapies on anti-citrullinated protein autoan 2013 Jul Rheumatoid arthritis (RA) is a complex inflammatory disorder associated with synovitis and joint destruction that affects an estimated 1·3 million Americans and causes significant morbidity, a reduced life-span and lost work productivity. The use of biological therapies for the treatment of RA is costly, and the selection of therapies is still largely empirical and not guided by the underlying biological features of the disease in individual patients. The synovitis associated with RA is characterized by an influx of B and T cells, macrophages and neutrophils and the expansion of fibroblast-like synoviocytes, which form pannus and lead to cartilage and bone destruction. RA is associated with synovial production of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) and with the production of inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-17 and tumour necrosis factor (TNF)-α, which are targets for RA therapeutics. Recent ideas about the pathogenesis of RA emphasize a genetic predisposition to develop RA, a preclinical phase of disease that is associated with the production of ACPA and the development of symptomatic disease following inflammatory initiating events that are associated with expression of citrullinated epitopes in the joints of patients. However, we still have a limited understanding of the cytokine and intracellular pathways that regulate ACPA levels. In humans, therapy with biological agents affords a unique opportunity to better understand the cytokine and signalling pathways regulating ACPA levels and the impact of ACPA level changes on disease activity. In this study we summarize the effect of RA therapies on ACPA levels and B cell responses.
22679298 The ability of synovitis to predict structural damage in rheumatoid arthritis: a comparati 2013 May OBJECTIVES: To evaluate synovitis (clinical vs ultrasound (US)) to predict structural progression in rheumatoid arthritis (RA). METHODS: Patients with RA. STUDY DESIGN: Prospective, 2-year follow-up. DATA COLLECTED: Synovitis (32 joints (2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal, 10 metatarsophalangeal)) at baseline and after 4 months of therapy by clinical, US grey scale (GS-US) and power doppler (PD-US); x-rays at baseline and at year 2. ANALYSIS: Measures of association (OR) were tested between structural deterioration and the presence of baseline synovitis, or its persistence, after 4 months of therapy using generalised estimating equation analysis. RESULTS: Structural deterioration was observed in 9% of the 1888 evaluated joints in 59 patients. Baseline synovitis increased the risk of structural progression: OR=2.01 (1.36-2.98) p<0.001 versus 1.61 (1.06-2.45) p=0.026 versus 1.75 (1.18-2.58) p=0.005 for the clinical versus US-GS versus US-PD evaluation, respectively. In the joints with normal baseline examination (clinical or US), an increased probability for structural progression in the presence of synovitis for the other modality was also observed (OR=2.16 (1.16-4.02) p=0.015 and 3.50 (1.77-6.95) p<0.001 for US-GS and US-PD and 2.79 (1.35-5.76) p=0.002) for clinical examination. Persistent (vs disappearance) synovitis after 4 months of therapy was also predictive of subsequent structural progression. CONCLUSIONS: This study confirms the validity of synovitis for predicting subsequent structural deterioration irrespective of the modality of examination of joints, but also suggests that both clinical and ultrasonographic examinations may be relevant to optimally evaluate the risk of subsequent structural deterioration.
24456966 Porphyromonas gingivalis oral infection exacerbates the development and severity of collag 2013 Nov 12 INTRODUCTION: Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model. METHODS: DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression. RESULTS: Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA/CII group and IL-1β, tumor necrosis factor-α, transforming growth factor-β, IL-6 and IL-23 in the IFA/CII group. CONCLUSIONS: Chronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.
23579879 Left ventricular morphology and function in patients with rheumatoid arthritis. 2013 May OBJECTIVES: Congestive heart failure (CHF) and inflammation are important contributors to the excess of overall morbidity and mortality in patients with rheumatoid arthritis (RA). CHF rather than ischaemic heart disease (IHD) appears to participate on the mortality in these patients. However, there are controversial results about significance of plasma N-terminal of pro-B type natriuretic peptide (NT-proBNP) and other inflammatory markers investigation for an early detection of heart dysfunction. The aim of this study was to examine the cardiac morphology and function in patients with RA in relation to the plasma NT-proBNP and to inflammatory markers. SUBJECTS AND METHODS: Sixty patients with RA (52 women and 8 men) and 30 gender and age matched controls were included in the study. Blood samples were analyzed for NT-proBNP, tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and C-reactive protein (CRP). Transthoracic echocardiography was performed on the same day in all subjects. RESULTS: RA patients had significantly higher plasma NT-pro BNP as compared with controls (99.39 ± 8.98 vs. 66.90 ± 7.93 pg/ml, p < 0.05) and significantly higher levels of TNF-alpha, IL-6 and CRP (for all p < 0.01). In RA group higher levels of NT-proBNP were detected in rheumatoid factor (RF) posivite patients. Patients with RA had significantly worse left ventriclular (LV) systolic function (LV ejection fraction (LVEF) 64.6 ± 0.8 vs. 70.1 ± 1.3 %, p < 0.01) and diastolic function (E/A 1.11 ± 0.05 vs. 1.32 ± 0.07, p < 0.05). There were no correlations of NT-proBNP with paramaters of systolic and diastolic function, however, a negative correlation of TNF-alpha with these parameters was detected (TNF-alpha vs. LV mass index (LVM-i): r = - 0.34, p < 0.05), TNF-alpha vs. LVEF: r = - 0.30, p < 0.05 and TNF-alpha vs. E/A: r = - 0.30, p < 0.05). CONCLUSION: We conclude that TNF-alpha may be better marker of heart impairment caused by chronic inflammation in RA patients than NT-proBNP.
23423442 Prevalence of and factors associated with vitamin D deficiency in 4,793 Japanese patients 2013 Jul To determine the prevalence of vitamin D deficiency and associations with clinical characteristics in Japanese patients with rheumatoid arthritis (RA), serum 25(OH)D levels, laboratory data, and clinical data were obtained from 4,793 patients with RA (4,075 women, 718 men, mean age 59.7 years) who participated in the Institute of Rheumatology Rheumatoid Arthritis observational cohort study in April and May of 2011. Serum vitamin D levels were evaluated using a radioimmunoassay. We defined vitamin D deficiency as <20 ng/mL and severe deficiency as <10 ng/mL. Associations of vitamin D deficiency with patient characteristics were examined using multivariate logistic regression. Among all patients, the mean (SD) serum 25(OH)D level was 16.9 ng/mL (6.1), and the prevalence of vitamin D deficiency and severe deficiency were 71.8 and 11.5%, respectively. In multivariate analysis, female gender, younger age, high Japanese version of health assessment questionnaire (HAQ) disability score, low serum total protein levels, low serum total cholesterol levels, high serum alkaline phosphate (ALP) levels, and non-steroidal anti-inflammatory drug (NSAID) use were significantly associated with vitamin D deficiency (P < 0.01). Vitamin D deficiency appears to be common in Japanese patients with RA, as previously reported for patients of other ethnicities. Female gender, younger age, high HAQ disability score, low serum levels of total protein and total cholesterol, high serum ALP levels, and NSAID use appear to be associated with vitamin D deficiency in Japanese patients with RA.
24960622 A case of peritoneal TB causing renal failure in a patient with rheumatoid arthritis and i 2014 Jul Opportunistic infection and reactivation of latent infection has been reported with use of monoclonal TNF alpha antibodies used for treatment of severe rheumatoid arthritis. We present a case of peritoneal tuberculosis (TB) causing renal failure secondary to ureteral constriction in a patient who had been treated with infliximab for rheumatoid arthritis. We suggest that physicians should be aware of the increased risk of false negative and false positive TST and IGRA among patients treated with monoclonal TNF alpha antibodies and should regularly look for usual and unusual symptoms of TB in this patient population.
23754245 Reduction of plasma IL-6 but not TNF-α by methotrexate in patients with early rheumatoid 2013 Nov OBJECTIVE: To determine the effect of methotrexate (MTX) on plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and to investigate their associations with clinical and radiographic responses in patients with early rheumatoid arthritis (RA). METHODS: Sixty-two untreated RA patients with the disease duration of ≤36 months in whom MTX was initiated were consecutively identified in our prospective RA cohort and included in this study. Concomitant use of prednisolone and synthetic disease-modifying anti-rheumatic drugs with MTX was allowed, but patients who used biological agents were excluded. Plasma IL-6 and TNF-α levels were measured at the time of diagnosis (baseline) and 1 year later. The relationships of the clinical and radiographic data with plasma levels of IL-6 and TNF-α were analyzed. RESULTS: The median age of the patients was 57 years, 49 patients were female, and the median disease duration was 3 months. Forty-six (74.2 %) patients were anti-cyclic citrullinated protein antibody-positive. Serum C-reactive protein (CRP), plasma IL-6, and DAS28 decreased significantly (p <0.001) after MTX treatment, but plasma TNF-α did not. Radiographic progression was significantly correlated with disease activity score and plasma IL-6 levels but not with CRP or TNF-α after MTX treatment. Patients with plasma IL-6 level above 4.03 pg/ml showed clinically relevant radiographic progression with a sensitivity of 91.7 % and a specificity of 88.0 %. CONCLUSION: In this early RA cohort, we demonstrated a significant (p <0.001) reduction of plasma IL-6, but not TNF-α, during MTX treatment. The post-treatment IL-6 level was a strong indicator of radiographic progression.