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ID PMID Title PublicationDate abstract
23950186 A randomized controlled trial of an internal family systems-based psychotherapeutic interv 2013 Nov OBJECTIVE: To conduct a proof-of-concept randomized trial of an Internal Family Systems (IFS) psychotherapeutic intervention on rheumatoid arthritis (RA) disease activity and psychological status. METHODS: Patients with RA were randomized to either an IFS group for 9 months (n = 39) or an education (control) group (n = 40) that received mailed materials on RA symptoms and management. The groups were evaluated every 3 months until intervention end and 1 year later. Self-assessed joint pain (RA Disease Activity Index joint score), Short Form-12 physical function score, visual analog scale for overall pain and mental health status (Beck Depression Inventory, and State Trait Anxiety Inventory) were assessed. The 28-joint Disease Activity Score-C-reactive Protein 4 was determined by rheumatologists blinded to group assignment. Treatment effects were estimated by between-group differences, and mixed model repeated measures compared trends between study arms at 9 months and 1 year after intervention end. RESULTS: Of 79 participants randomized, 68 completed the study assessments and 82% of the IFS group completed the protocol. Posttreatment improvements favoring the IFS group occurred in overall pain [mean treatment effects -14.9 (29.1 SD); p = 0.04], and physical function [14.6 (25.3); p = 0.04]. Posttreatment improvements were sustained 1 year later in self-assessed joint pain [-0.6 (1.1); p = 0.04], self-compassion [1.8 (2.8); p = 0.01], and depressive symptoms [-3.2 (5.0); p =0.01]. There were no sustained improvements in anxiety, self-efficacy, or disease activity. CONCLUSION: An IFS-based intervention is feasible and acceptable to patients with RA and may complement medical management of the disease. Future efficacy trials are warranted. ClinicalTrials.gov identifier: NCT00869349.
23621997 Metabolic syndrome in rheumatoid arthritis: case control study. 2013 Apr 26 BACKGROUND: Metabolic syndrome, a cluster of classical cardiovascular risk factors, including hypertension, obesity, glucose intolerance, and dyslipidemia is highly prevalent in patients with rheumatoid arthritis (RA). The aim of the study was to assess the frequency of metabolic syndrome (MS) in RA patients, and to evaluate the relationships between metabolic syndrome and RA. METHODS: The study was conducted on 120 RA patients according to the 1987 revised American College of Rheumatology classification criteria, and 100 age and sex matched apparently healthy controls. The frequency of metabolic syndrome was assessed using six Metabolic Syndrome definitions (Joint Consensus 2009, National Cholesterol Education Programme 2004 and 2001, International Diabetes Federation, World Health Organisation and European Group for Study of Insulin Resistance). Logistic regression was used to identify independent predictors of metabolic Syndrome. RESULTS: The frequency of metabolic syndrome varied from 18 to 48.6% in RA according to the definition used and was significantly higher than controls (for all definitions p<0.05). In multivariate analysis, higher ESR was independently associated with the presence of Met S (OR =1.36; CI: 1.18-2.12; p = 0.03). Glucocorticoid use, but not other disease modifying anti-rheumatic drugs (DMARDs), values remained significant independent predictors of the presence of metabolic syndrome in RA patients (OR = 1.45; CI: 1.12-2.14; p = 0.04). CONCLUSIONS: In summary, the frequency of metabolic syndrome in RA varies according to the definition used and was significantly higher compared to controls (for all definitions p<0.05). Higher systemic inflammatory marker, and glucocorticoids use were independent predictors associated with the presence of metabolic syndrome in patients with RA. These findings suggest that physicians should screen for metabolic syndrome in patients with RA to control its components and therefore reduce the risk of cardiovascular disease in these patients.
24719981 Relevance of indirect immunofluorescence patterns and autoantibodies identified via line i 2014 Winter OBJECTIVE: To analyze indirect immunofluorescence (IIF) patterns and autoantibodies identified by line immunoassay (LIA) in rheumatoid arthritis (RA) patients, and to compare the autoantibody profiles with serological markers to determine their relevance. METHODS: A total of 153 specimens were obtained from RA patients for diagnostic or monitoring purposes. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) were measured, and autoantibody testing using IIF and LIA was performed. Frequencies of IIF patterns and autoantibodies identified by LIA were analyzed and compared with each other and with serologic markers of RF, including anti-CCP, ESR, and CRP. RESULTS: The overall positivity of IIF and LIA results was 49.7% and 34.0%, respectively. The most frequent IIF pattern in RA was homogenous (20.9%), followed by dense fine speckled (DFS) pattern (17%). Anti-SS-A and/or anti-Ro-52 were most frequently detected in RA irrespective of the observed IIF pattern. Positive rates and intensities of autoantibodies detected did not differ by therapeutic regimen or disease activity, as reflected by CRP levels or ESR. Only anti-CCP showed a tendency to increase depending on IIF intensity. CONCLUSIONS: RA patients did not display a specific or dominant IIF pattern or autoantibody presence, as identified by LIA. RA patients had lower frequencies of anti-SS-A and anti-Ro-52 compared with other systemic autoimmune diseases (serologically characteristic of RA). IIF and LIA appear insufficient for diagnosing RA and monitoring disease activity yet can be useful for screening and differentiating major systemic autoimmune diseases.
25391609 Three decades of low-dose methotrexate in rheumatoid arthritis: can we predict toxicity? 2014 Dec Methotrexate (MTX) is the anchor disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA) treatment. It is used in monotherapy and/or in combination with other synthetic or biological DMARDs, and is known to have the best cost-effectiveness and efficacy/toxicity ratios. However, toxicity is still a concern, with a significant proportion of patients interrupting long-term treatment due to the occurrence of MTX-related adverse drug reactions (ADRs), which are the main cause of drug withdrawal. Despite the extensive accumulated experience in the last three decades, it is still impossible in routine clinical practice to identify patients prone to develop MTX toxicity. While clinical and biological variables, including folate supplementation, partially help to minimize MTX-related ADRs, the advent of pharmacogenomics could provide further insight into risk stratification and help to optimize drug monitoring and long-term retention. In this paper, we aimed to review and summarize current data on low-dose MTX-associated toxicity, its prevention and predictors, keeping in mind practical RA clinical care.
25152090 The relationship between cardiovascular disease risk prediction scores and vascular functi 2014 Nov OBJECTIVES: Patients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease (CVD) resulting from impairments in vascular function and morphology. CVD risk prediction scores can identify patients at high risk of CVD, but little is known about whether they relate with assessments of vascular function and morphology which provide early indication of subclinical atherosclerosis. The objective of the present study was to examine the relationship of several CVD risk prediction scores with assessments of vascular function and morphology in patients with RA. METHODS: Framingham risk score, Systematic Coronary Risk Evaluation for total cholesterol and ratio of total cholesterol to high-density lipoprotein, as well as Reynolds Risk Score, and QRISK2 were calculated in 201 RA patients (155 females, median (25th to 75th percentile) age: 61 (53-67)) who were examined at baseline (2006). The European League Against Rheumatism (EULAR) multiplication factor was also applied to the algorithms. At a 6-year follow-up (2012) visit the patients underwent assessments of microvascular and macrovascular endothelium-dependent and endothelium-independent function, along with assessment of carotid atherosclerosis. RESULTS: All five CVD risk prediction scores measured at baseline were significantly correlated with vascular function and morphology at follow-up. Application of the EULAR multiplication factor did not change any of the associations. CONCLUSIONS: Five commonly used CVD risk prediction scores associate with assessments of vascular function and morphology over a 6-year follow-up period suggesting that these CVD risk prediction scores may also reflect subclinical atherosclerotic changes.
24939676 Does ultrasound-scored synovitis depend on the pharmacokinetics of subcutaneous anti-TNF a 2014 Nov OBJECTIVE: The aim of this study was to investigate the influence of the pharmacokinetics of s.c. anti-TNF agents on the grade of US-detected synovitis in RA patients. METHODS: Fifty RA patients were prospectively recruited from the Biologic Therapy Unit of our hospital. Inclusion criteria were being in treatment with s.c. anti-TNF agents and having had neither changes in therapy nor local corticosteroid injections in the previous 3 months. Patients underwent clinical, laboratory [28-joint DAS (DAS28) and Simplified Disease Activity Index (SDAI)] and US assessment at two time points, i.e. at peak plasma drug concentration and at trough plasma drug concentration. US assessments were performed blindly to the anti-TNF agent, the administration time and the clinical and laboratory data. Twenty-eight joints were investigated for the presence and grade (0-3) of B-mode synovitis and synovial power Doppler signal. Global indices for B-mode synovitis (BSI) and Doppler synovitis (DSI) were calculated for 12 joints and for wrist-hand-ankle-foot joints. B-mode US remission was defined as a BSI <1 and Doppler US remission as a DSI <1. RESULTS: There were no significant differences between the clinical, laboratory and B-mode and Doppler US parameters at peak time and trough time (P = 0.132-0.986). There were no significant differences between the proportion of patients with active disease and those in remission according to DAS28, SDAI, B-mode US and Doppler US at peak time and trough time assessments (P = 0.070-1). CONCLUSION: Our results suggested that s.c. anti-TNF pharmacokinetics do not significantly influence US-scored synovitis in RA patients.
24752345 Responsiveness of the EuroQol EQ-5D and Hospital Anxiety and Depression Scale (HADS) in rh 2014 Aug The aim of this study was to assess the responsiveness to change of the quality of life evaluated by the EuroQol Five Dimensions Questionnaire (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) after biological treatment in a population of rheumatoid arthritis patients. A cohort of patients with RA (n = 29) treated with tocilizumab (TCZ) were analyzed in the study. The inclusion criteria were patients aged between 18 and 65 years, fulfilling American College of Rheumatology 1987 criteria for RA. All patients had inadequate response to methotrexate and with no prior biologic exposure. They were evaluated clinically including Disease Activity Score 28 (DAS28), and the European Quality of Life 5 Dimensions (EQ-5D) to measure the quality of life, and HAD assessed the anxiety and depression status at the initiation of treatment with anti-IL 6 receptor antibody agent and after 6 months. Sensitivity to change was quantified by the effect size (ES) before and after the treatment with TCZ. Among 29 patients with RA included in the study, 25 were females and 4 males. The mean age was 42 years ± 13.4 (SD). Three patients were excluded from the study before 24 weeks because of serious side effects, and five have missing data. The study population exhibited significant decreases in all measures of disease activity at 24 weeks. Physical activity expressed by the Health Assessment Questionnaire (HAQ) score increased through the observation period (for all p < 0.001). Sensitivity to change was high for the VAS and EQ-5D (ES 1.58 and 1.36, respectively) but only moderate for the HAD anxiety component (ES = 0.70) and small for the HAD depression component (ES = 0.4). The EQ-5D and VAS were more responsive than HADS to evaluate the quality of life on patient with RA treated with TCZ.
23688612 Ocular manifestations of the potentially lethal rheumatologic and vasculitic disorders. 2013 Jun Vision threatening ocular inflammation may occur in patients with any of the acquired connective tissue disorders and vasculitic diseases. Additionally, the ocular inflammation may be the presenting manifestation of the disease, which leads the patient to seek medical care. Other manifestations of the potentially lethal disease may be subtle or absent, presenting the thoughtful ophthalmologist with the opportunity to make life saving discoveries. Necrotizing scleritis, peripheral ulcerative keratitis, and retinal vasculitis are the ocular findings which should prompt the ophthalmologist to initiate very aggressive measures aimed at discovering any evidence of extra-ocular abnormalities, laboratory or otherwise. Appropriate therapy will be sight saving and may be life saving.
25352417 Psychiatric and cardiovascular comorbidities as causes of long-term work disability among 2015 OBJECTIVES: With the ameliorating prognosis of rheumatoid arthritis (RA), the role of comorbidities as causes of work disability (WD) may increase. The aim of this study was to determine the contribution of psychiatric and cardiovascular (CV) comorbidities as the leading causes of long-term WD among patients with recent-onset RA. METHOD: Between 2000 and 2007, all incident, working-age and non-retired RA patients were identified from a Finnish nationwide register. From other registers, we identified the RA patients who were granted a permanent or temporary disability pension by 31 December 2008. The incidences of disability pensions with CV diseases (ICD-10 codes I00-I99) or psychiatric disorders (F20-F69) as the leading causes were assessed and compared with the general population. RESULTS: We identified a cohort of 7831 patients with RA. During follow-up, 1095 patients were granted a disability pension. After adjusting for competing risks, the 9-year cumulative incidence of WD caused by RA, a psychiatric comorbidity, or a CV disease was 11.9, 1.3, and 0.5%, respectively. Compared to the general population, the age- and sex-specific standardized incidence ratio (SIR) of WD due to psychiatric comorbidities was 0.99 [95% confidence interval (CI) 0.80-1.23] and due to CV disease 1.75 (95% CI 1.23-2.51). CONCLUSIONS: In the study cohort with recent-onset RA, the 9-year cumulative incidence of disability pensions caused by psychiatric or CV comorbidities was only 11% or 4%, respectively, of that caused by RA itself. Compared to the general population, the risk of WD due to CV disease was increased.
24465874 IFNα serum levels are associated with endothelial progenitor cells imbalance and disease 2014 INTRODUCTION: IFNα has been largely implicated in the ethiopathogenesis of autoimmune diseases but only recently it has been linked to endothelial damage and accelerated atherosclerosis in autoimmunity. In addition, proinflammatory conditions are supposed to be implicated in the cardiovascular status of these patients. Since a role for IFNα in endothelial damage and impaired Endothelial Progenitor Cell (EPC) number and function has been reported in other diseases, we aimed to evaluate the potential associations of IFNα serum levels on EPC populations and cytokine profiles in Rheumatoid Arthritis (RA) patients. METHODS: pre-EPC, EPC and mature EPC (mEPC) populations were quantified by flow cytometry analyzing their differential CD34, CD133 and VEGFR2 expression in blood samples from 120 RA patients, 52 healthy controls (HC), and 83 systemic lupus erythematosus (SLE) patients as disease control. Cytokine serum levels were measured by immunoassays and clinical and immunological data, including cardiovascular (CV) events and CV risk factors, were retrospectively obtained by reviewing clinical records. RESULTS: Long-standing, but not recent onset RA patients displayed a significant depletion of all endothelial progenitor populations, unless high IFNα levels were present. In fact, the IFN(high) RA patient group (n = 40, 33%), showed increased EPC levels, comparable to SLE patients. In addition, high IFNα serum levels were associated with higher disease activity (DAS28), presence of autoantibodies, higher levels of IL-1β, IL-6, IL-10 and MIP-1α, lower amounts of TGF-β, and increased mEPC/EPC ratio, thus suggesting higher rates of endothelial damage and an endothelial repair failure. Finally, the relationship between high IFNα levels and occurrence of CV events observed in RA patients seems to support this hypothesis. CONCLUSIONS: IFNα serum marker could be used to identify a group of RA patients with increased disease activity, EPC imbalance, enhanced proinflammatory profile and higher cardiovascular risk, probably due, at least in part, to an impaired endothelial repair.
22669600 Improvement of health status evaluated by Arthritis Impact Measurement Scale 2 (AIMS-2) an 2013 Mar OBJECTIVE: To evaluate the improvement of health status in patients with rheumatoid arthritis (RA) treated with tocilizumab. METHODS: Thirty-nine patients were treated with 8 mg/kg tocilizumab every 4 weeks for 24 weeks. Disease activity was assessed by Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). Improvement of health status was assessed by Arthritis Impact Measurement Scale 2 (AIMS-2) and Short Form-36 (SF-36). RESULTS: Tocilizumab improved CDAI and SDAI significantly at week 4 compared with at baseline. In the components of AIMS-2, "physical score", "symptom" and "affect" improved significantly at week 4 compared with at baseline, while "social interaction" did not improve significantly during 24 weeks of tocilizumab therapy. Similarly in SF-36, "bodily pain", "general health", "vitality" and "mental health" improved significantly at week 4. The most correlative component of AIMS-2 with CDAI was "symptom", while "social interaction" did not correlate with CDAI during tocilizumab treatment. CONCLUSION: The time-course diversity in improvement of health status should be considered to provide proper healthcare when treated with tocilizumab.
23877712 Anti-Proteus activity of some South African medicinal plants: their potential for the prev 2014 Feb A wide variety of herbal remedies are used in traditional African medicine to treat rheumatoid arthritis (RA) and inflammation. Thirty-four extracts from 13 South African plant species with a history of ethnobotanical usage in the treatment of inflammation were investigated for their ability to control two microbial triggers for RA (Proteus mirabilis and Proteus vulgaris). Twenty-nine of the extracts (85.3 %) inhibited the growth of P. mirabilis and 23 of them tested (67.7 %) inhibited the growth of P. vulgaris. Methanol and water extracts of Carpobrotus edulis, Lippia javanica, Pelargonium viridflorum, Ptaeroxylon obliquum, Syzygium cordatum leaf and bark, Terminalia pruinoides, Terminalia sericea, Warburgia salutaris bark and an aqueous extract of W. salutaris leaf were effective Proteus inhibitors, with MIC values <2,000 μg/ml. The most potent extracts were examined by Reverse phase high performance liquid chromatography and UV-Vis spectroscopy for the presence of resveratrol. Only extracts from T. pruinoides and T. sericea contained resveratrol, indicating that it was not responsible for the anti-Proteus properties reported here. All extracts with Proteus inhibitory activity were also either non-toxic, or of low toxicity in the Artemia nauplii bioassay. The low toxicity of these extracts and their inhibitory bioactivity against Proteus spp. indicate their potential for blocking the onset of rheumatoid arthritis.
24129132 Discontinuation of biologics in patients with rheumatoid arthritis. 2013 Jul The use of early aggressive treatment combined with the availability of biological agents targeting pro-inflammatory cytokines such TNF and IL-6 has greatly advanced the treatment of rheumatoid arthritis (RA). Clinical remission is a realistic primary goal and its maintenance leads to stabilisation of structural deterioration and functional remission. With the achievement of sustained remission, discontinuation of biological agents has emerged as an important consideration, with subsequent reductions in medication-induced side effects and health costs. Evidence from studies suggests that MTX-naïve, early RA patients can achieve sustained biologic-free remission with no functional or radiographic progression, after treatment with combination TNF inhibitors and MTX. For patients with long-standing RA and who have previous inadequate responses to MTX, the evidence for sustained biologic-free remission is less convincing. The discontinuation of TNF-inhibitors after sustained remission has been shown to be possible in some long-standing RA patients with inadequate response to MTX, particularly in Japanese patients. However, high flare rates and adverse long-term outcomes have been documented in other studies. For these patients a biologic dose-reduction regimen may be preferable. The combination of early treatment with TNF inhibitors and MTX plus tight control of inflammation provide the best chance of a biologic-free remission or at least the possibility of 'biologic treatment holidays'.
23613766 Associations between APOE genotypes and disease susceptibility, joint damage and lipid lev 2013 OBJECTIVE: Apolipoprotein E (APOE) genotypes are associated with cardiovascular disease (CVD) and lipid levels. In rheumatoid arthritis (RA), an association has been found with disease activity. We examined the associations between APOE genotypes and disease susceptibility and markers of disease severity in RA, including radiographic joint damage, inflammatory markers, lipid levels and cardiovascular markers. METHOD: A Norwegian cohort of 945 RA patients and 988 controls were genotyped for two APOE polymorphisms. We examined longitudinal associations between APOE genotypes and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) as well as hand radiographs (van der Heijde Sharp Score(SHS)) in 207 patients with 10 year longitudinal data. Lipid levels, cardiovascular markers and history of CVD were compared across genotypes in a cross sectional study of 136 patients. Longitudinal radiological data of cohorts from Lund and Leiden were available for replication. (N = 935, with 4799 radiographs). RESULTS: In the Norwegian cohort, associations between APOE genotypes and total cholesterol (TC) and low-density lipoproteins (LDL) were observed (ε2 < ε3/ε3 < ε4, p = 0.03 and p = 0.02, respectively). No association was present for acute phase reactant or CVD markers, but a longitudinal linear association between APOE genotypes and radiographic joint damage was observed (p = 0.007). No association between APOE genotypes and the severity of joint destruction was observed in the Lund and Leiden cohorts, and a meta- analysis combining all data was negative. CONCLUSION: APOE genotypes are associated with lipid levels in patients with RA, and may contribute to dyslipidemia in some patients. APOE genotypes are not consistently associated with markers of inflammation or joint destruction in RA.
24998790 High anti-CCP antibody titres predict good response to rituximab in patients with active r 2014 Oct OBJECTIVE: Previous studies reported that anti-CCP antibody positivity predicts good response to rituximab (RTX) in rheumatoid arthritis (RA). A quantitative approach to such possibility could be a good way to detect the subset of patients most likely to respond. We investigated whether serum anti-CCP antibody titres could predict response to RTX in RA patients. METHODS: We retrospectively investigated RA patients who received RTX. The primary criterion was decrease in DAS28>1.2 at 6months (M6). Secondary efficacy criteria included a good response and remission according to EULAR. Predictors of response were investigated by multivariate logistic regression analysis. RESULTS: We included 114 RA patients (81.6% female, median age 53.5 [IQR 45.7-61.2] years, median disease duration 8.5 [4.0-16.0] years). Anti-CCP antibodies were present in 93 patients (81.6%), with median anti-CCP antibody titres 583 [195-1509] U/mL. In all, 44 patients (38.6%) showed decreased DAS28>1.2 at M6. On univariate analysis, high anti-CCP titres were associated with response rather than non-response to RTX (median 1122 [355-1755] vs. 386 [149-800] U/mL, P=0.0191) at M6. On multivariate regression analysis, with a cut-off of 1000 U/mL, anti-CCP antibody titres≥1000 was associated with a decrease in DAS28>1.2 (OR 5.10 [1.97-13.2], P=0.0002); a EULAR good response (4.26 [1.52-11.95], P=0.0059); and a trend for EULAR remission (2.52 [0.78-8.12], P=0.1207). CONCLUSION: High anti-CCP antibody titres predict response to RTX in RA. This factor, easily assessed in clinical practice, can help with personalized medicine and selecting the best candidates for RTX treatment.
24692573 Standard and pocket-size lung ultrasound devices can detect interstitial lung disease in r 2014 Aug OBJECTIVES: Interstitial lung disease (ILD) is a frequent extra-articular manifestation of RA associated with increased mortality. High-resolution CT (HRCT) is used for diagnosis and follow-up, but its accuracy is counterbalanced by high costs and radiological risk. In the presence of ILD, lung US (LUS) detects vertical artefacts called B-lines. The aims of the present study were to evaluate the accuracy of LUS in the diagnosis of ILD in RA and to validate the use of a pocket-size US device (PS-USD) as a screening tool. METHODS: LUS was performed with standard equipment by a trained physician through longitudinal scans following anatomical lines: 72 segments were considered (28 anteriorly and 44 posteriorly) and B-lines were counted in each segment. A B-lines score >10 identified a positive examination (presence of ILD). A second LUS session for positive/negative judgment was performed by a short-trained physician using a PS-USD. RESULTS: Thirty-nine patients were studied. The sensitivity and specificity of standard LUS vs HRCT were 92% and 56%, respectively. The B-line score was significantly correlated with HRCT score (r = 0.806). A total of 29 patients were studied with a PS-USD. Sensitivity and specificity for PS-USD vs HRCT were 89% and 50%. CONCLUSION: The sensitivity of LUS in the detection of ILD supports its use as a screening test for ILD in RA patients, even in the ambulatory setting with a PS-USD. The strong correlation between echographic and HRCT scores indicates LUS is a valid tool for grading and follow-up of ILD.
24273974 [Correlation research on the expression of FcgammaR II b on B cells and rheumatoid arthrit 2013 Sep OBJECTIVE: To study the correlation between the expression of Fcgamma receptor II b (FcgammaRII b) on B cells and rheumatoid arthritis (RA) patients of Shen deficiency syndrome (SDS). METHODS: There were 43 RA patients, including 26 of SDS and 17 of non-SDS. The expression levels of FcgammaRII b on naive B cells, memory B cells, and plasma blasts in the peripheral blood were detected by flow cytometry. The numbers of tender joints, numbers of swollen joints, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and disease activity score (DAS28), the correlation between the distribution of B cells and the expression level of FcgammaRII b in RA patients were analyzed. Besides, another 21 healthy volunteers were recruited as the control group. RESULTS: The expression level of FcgammaRII b was 49.65% +/- 15.86% on memory B cells and 43.69% +/- 22.57% on plasma blasts in RA patients of SDS, significantly down-regulated when compared with those of the control group (64.03% +/- 6.01%, 66.59% +/- 10.18%, P < 0.01). The expression level of FcgammaRII b on memory B cells of RA patients of non-SDS was down-regulated more obviously when compared with that of the control group (52.70% +/- 9.52% versus 64.03% +/- 6.01%, P < 0.01). The expression level of FcgammaRII b on plasma blasts was obviously lower in RA patients of SDS than in RA patients of non-SDS (56.10% +/- 17.05%, P < 0.05). The expression level of FcgammaRII b on memory B cells was not correlated with numbers of tender joints, numbers of swollen joints, ESR, RF, or DAS28. CONCLUSIONS: The defective immunological tolerance of B cells in RA patients of SDS might be closely correlated with down-regulation of FcgammaRII b on memory B cells and plasma blasts. There might exist genetic abnormality of FcgammaRII b gene in RA patients of SDS, thus inducing loss of autoimmunity tolerance.
23239231 Role of cadherin-11 in synovial joint formation and rheumatoid arthritis pathology. 2013 Nov Cadherin-11 is a classic cadherin adhesion molecule that mediates homophilic cell-to-cell adhesion. Cadherin-11 is involved in the function of embryonic development, tissue morphogenesis, tumor invasion and metastasis, and signal transduction. This review summarizes the function of cadherin-11 in synovial joint formation and rheumatoid arthritis (RA), including its relative function with bone and cartilage development and growth plate, synovial, and tendon formation. The role of cadherin-11 in RA is also discussed, both in fibroblasts inflammation and fibroblast-like synoviocyte (FLSs) migration and invasion. The potential of anti-cadherin-11 therapy for RA is introduced in comparison with the other current RA therapies.
25194333 Relationship between dimethylarginine dimethylaminohydrolase gene variants and asymmetric 2014 Nov OBJECTIVE: The aim of our study was to determine whether Dimethylarginine Dimethylaminohydrolase (DDAH) 1 and 2 gene polymorphisms - the main enzyme involved in ADMA degradation - are associated with high Asymmetric Dimethylarginine (ADMA) levels in Rheumatoid Arthritis (RA). METHODS: Serum ADMA levels were measured in 201 individuals with RA [155 females median age 67 (59-73)]. Four tag SNPs in DDAH1 gene and 2 in the DDAH2 gene were genotyped by using the LightCyclerâ„¢ System. ADMA was initially compared across the genetic variables using one-way ANOVA and then multivariate analysis examined each of the genes after adjustment for parameters of systemic inflammation and insulin resistance, namely erythrocyte sedimentation rate (ESR) and homeostatic model assessment (HOMA), which we have previously shown affect ADMA levels in RA. RESULTS: No significant relationship between DDAH genetic variables and ADMA levels was established in ANOVA analysis. Multivariate model adjusted for age, HOMA and ESR did not demonstrate any significant association between DDAH variants and ADMA. CONCLUSION: The results of our study give no evidence to suggest that increased ADMA levels in RA relate to DDAH genetic polymorphisms. Better understanding of disease-related factors and their interactions with traditional CV risk factors may represent mechanisms responsible for ADMA accumulation in this population.
25108207 Association between serum uric acid and inflammation in rheumatoid arthritis: perspective 2015 Jan 1 BACKGROUND: The association between serum uric acid concentrations and inflammation in patients with rheumatoid arthritis (RA) has been still controversial. METHODS: A total of 172 patients with RA who added leflunomide to methotrexate (MTX) in their treatment regimens were enrolled in this study. Twenty-seven RA patients taking MTX without leflunomide were also recruited in order to assess the fractional excretion of uric acid (FEUA). RESULTS: After leflunomide therapy for an average of 4.6months, serum uric acid concentrations had significantly decreased compared to baseline concentrations (p<0.001). Patients treated with a combination of MTX and leflunomide (n=23) showed higher FEUA than those treated with only MTX (n=27) (p=0.007). Differences in serum uric acid concentrations after leflunomide therapy were significantly associated with those in serum creatinine concentrations (B coefficient=3.081, p<0.001), but not with those in acute phase reactants including ESR and CRP. CONCLUSION: This study determined that leflunomide reduced serum uric acid concentrations through increased urinary excretion of uric acid, which might not reflect changes in disease activity status in RA. This implies that uric acid may not influence systemic inflammation in RA.