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ID PMID Title PublicationDate abstract
23661460 CTLA-4 and CD86 genetic variants and haplotypes in patients with rheumatoid arthritis in s 2013 Apr 25 The cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecule (CD80/CD86) genes are important susceptibility genes associated with autoimmune diseases. CTLA-4 polymorphisms have been found to be associated with various autoimmune diseases. However, the association data are inconsistent for rheumatoid arthritis (RA). We investigated the genetic association of CTLA-4 and CD86 polymorphisms with RA in a Chinese population. Four single nucleotide polymorphisms (SNPs) (rs5742909 and rs231775 in CTLA-4, and rs17281995 and rs1129055 in CD86) were genotyped in 213 patients with RA and 303 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele distributions of rs5742909 differ significantly between RA patients and controls (P < 0.05) and the dominant model was found to be the best inheritance model. Stratification studies showed that CTLA-4 gene polymorphisms were more significantly associated with rheumatoid factor-negative and anti-cyclic citrullinated peptide-negative subgroups in the southeastern Han Chinese population. We also found that the haplotype of 2 CTLA-4 SNPs showed significant association with the disease (P = 0.0025) with the T-A (OR = 1.88, 95%CI = 1.12-3.15) and T-G (OR = 3.45, 95%CI = 1.10-10.87) haplotypes being observed more frequently in cases than in controls. We failed to find any significant association of the 2 CD86 SNPs with RA. These results indicate that the polymorphisms of CTLA-4 (rs5742909) may be important genetic factors for RA risk in the southeastern Han Chinese population.
23515597 Adherence to treatment in patients with ankylosing spondylitis. 2013 Jul This study aims to determine the level of adherence to treatment in ankylosing spondylitis (AS) patients and to identify possible factors associated to lack of adherence. We included consecutive AS patients (NY modified criteria). Sociodemographic and clinical data were collected. Patients answered auto-reported questionnaires: Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life, and Center for Epidemiological Studies Depression scale. Patients with rheumatoid arthritis (RA) (ACR'87 criteria) were assessed as the control group. The adherence of the studied groups to medical treatment and exercises was measured by means of two questionnaires: Compliance Questionnaire on Rheumatology (CQR) and Exercise Attitude Questionnaire-18 (EAQ-18). The study included 59 patients with AS and 53 patients with RA. Of the AS patients, 43 (72.9%) were male, median age 47 years (interquartile range (IQR) 33-57) and median disease duration of 120 months (IQR 33-57). Of the RA patients, 37 (69.8%) were female, had a median age of 56 years (IQR 43.5-60) and a median disease duration of 156 months (IQR 96-288). There were no significant differences in the results of the adherence questionnaires between both groups, with a total median of 68.42 for the CQR in both groups and of 40.7 in AS vs. 42.6 in RA for the EAQ. When dichotomizing patients as adherent and non-adherent, taking as good adherence a cut value in the CQR and EAQ higher than 60, adherence to pharmacological treatment was significantly higher in RA vs. AS (92.5 vs. 74.6%, p = 0.01) and there were no differences in the EAQ. On the uni- and multivariate analysis, lack of adherence to treatment was not associated to sex, age, disease duration, education, health insurance, depressive status, and disease activity parameters in neither group of patients. AS have an acceptable adherence to pharmacological treatment, although it is lower than RA patients; nonetheless, both groups show a lack of adherence to exercise.
23124653 Vitamin K2 administration is associated with decreased disease activity in patients with r 2013 Sep OBJECTIVES: Vitamin K2 (VitK2) is reported to induce not only bone mineralization of human osteoblasts and apoptosis of osteoclasts, but also apoptosis of rheumatoid arthritis (RA) synovial cells, while its clinical effect on disease activity of RA remains unknown. METHODS: 158 female RA patients (mean age 62.5 years) who had not been treated with warfarin, biologics, or teriparatide were enrolled in this study. VitK2 (45 mg/day) was administered in 70 patients with a serum undercarboxylated osteocalcin level of >4.5 ng/ml or with decreased bone mineral density in spite of the treatment with other anti-osteoporosis medications, regardless of RA disease activity. A longitudinal study was conducted in 52 patients who were additionally treated with VitK2 without changing their other medications for three months. RESULTS: In the cross-sectional study, as compared to the VitK2-naïve group (n = 88), the VitK2-treated group (n = 70) showed lower serum CRP (1.7 ± 0.2 vs. 0.5 ± 0.1 mg/dl; P < 0.001), MMP-3 (220.4 ± 21.9 vs. 118.0 ± 14.4 ng/ml; P < 0.001), and DAS28-CRP (2.9 ± 0.1 vs. 2.4 ± 0.1; P < 0.05). In the longitudinal study, patients who were additionally treated with VitK2 showed significant decreases in serum CRP (1.1 ± 0.2 to 0.6 ± 0.2 mg/dl; P < 0.001), MMP-3 (160.1 ± 25.6 to 125.0 ± 17.8 ng/ml; P < 0.05), and DAS28-CRP (3.1 ± 0.2 to 2.4 ± 0.1; P < 0.001). CONCLUSIONS: VitK2 may have the potential to improve disease activity besides osteoporosis in RA.
24702788 Diminished soluble levels of growth arrest specific protein 6 and tyrosine kinase receptor 2017 Jan AIM: Growth arrest specific protein 6 (Gas-6) and its tyrosine kinase receptor Axl plays an important role in apoptosis, and regulation of innate immune response, therefore, we investigated their plasma concentrations in Rheumatoid arthritis (RA) patients and correlated them to clinical, laboratory and radiological parameters of the disease. METHODS: Plasma from 77 RA patients and 50 normal healthy subjects were assayed for plasma Gas6 and Axl levels. Demographic, clinical and serological data were prospectively assessed. Rheumatoid arthritis disease activity was assessed using 28-joint Disease Activity Score (DAS-28) and functional capacity by modified health assessment questionnaire (mHAQ). Standardized x-rays for hands and feet were done to all participants. RESULTS: The level of Gas6 and Axl were significantly decreased in the RA patients compared to those of the healthy control subjects. Levels of Gas6 correlated positively with Axl levels in both patients and healthy control. Gas6 levels were remarkably reduced in those patients with erosive RA than those without. Levels of Gas6 were found to be negatively correlated with the presence of erosive disease and positively correlated with DAS-28, ESR, Leucocytosis and IL6. CONCLUSION: The plasma concentrations of Gas6 and Axl are altered in RA patients and thus may have a role in RA pathogenesis. Further mechanistic studies on the involvement of all TAM receptors tyrosine kinases pathway in RA are needed to help in understanding the pathogenesis and possibly aid in diagnosis and future treatments of RA especially for patients with erosive disease.
24140761 Treatment of rheumatoid arthritis with etanercept with reference to disease-modifying anti 2014 Jan OBJECTIVE: The objective of this study was to examine the long-term safety of etanercept (ETN) in comparison with conventional DMARDs in a large observational cohort of RA patients in the UK. METHODS: Data were made available from the British Society of Rheumatology Biologics Register for a cohort of patients with RA treated with ETN and a reference cohort of RA patients treated with conventional DMARDs (maximum follow-up 10 years). The adjusted risk of events was compared using Cox proportional hazards models. RESULTS: There were 3529 eligible ETN-treated patients (16,919 person-years) and 2864 conventional DMARD-treated patients (11,095 person-years), with notable differences between groups at baseline. Crude mortality rates were 12.0 vs 20.1 events per 1000 person-years for ETN and conventional DMARD patients, respectively, with an adjusted hazard ratio (aHR) of 0.72 (95% CI 0.54, 0.96). There was no difference in the long-term risk of serious infections (aHR = 1.02, 95% CI 0.83, 1.25). However, the risk was increased for ETN in the first 2 years (aHR = 1.56, 95% CI 1.16, 2.09; aHR = 1.32, 95% CI 1.06, 1.65). The aHRs (95% CIs) of various outcomes were cancer, 0.84 (0.68, 1.03); lymphoproliferative malignancy specifically, 0.51 (0.28, 0.95); all other serious adverse events, 0.70 (0.56, 0.87) and cardiac events specifically, 0.52 (0.37, 0.72). CONCLUSION: There was no evidence of adverse outcome from long-term exposure to ETN. There was evidence of improved survival, reduced cardiovascular events and reduced lymphoproliferative malignancies.
23657913 Treatment changes and improved outcomes in RA: an overview of a large inception cohort fro 2013 Aug OBJECTIVE: The introduction of effective treatment strategies in the past two decades has changed the management of RA dramatically. The objective was to analyse the changes in disease activity, function, joint damage and incidence of orthopaedic surgery over a period of 20 years (1989-2009) for patients with RA. METHODS: Data acquired from 1989 to 2008 inclusive from the Nijmegen RA inception cohort were studied. By repeated measures analysis the course of the population mean disease activity score (DAS28) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) corrected for age, gender, RF and disease duration was determined. Orthopaedic interventions were analysed as incidence rates with a Poisson distribution. We calculated the prevalence of the various therapies that patients were receiving. RESULTS: By 2009, 992 patients with RA had been included and 273 had been excluded. From 1989 onwards, the proportion of patients using MTX increased from 5% (8 of 164) to 62% (486 of 780), and biologic response modifiers from 0% to 22% (168 of 780) in 2008. The average MTX dosage increased to 16.1 ± 5.5 mg/week in 2008. The mean DAS28 (3.1) and HAQ-DI (0.47) were least (P < 0.008) in 2008 compared with previous years. There was a significant trend towards lower incidence rates of orthopaedic intervention in the period 2006-2008 than in almost all previous years. CONCLUSION: Treatment strategy changed in a large inception cohort of patients with RA which coincided with decreased disease activity, increased functional ability and fewer orthopaedic interventions since the early 1990s.
25438096 In patients with rheumatoid arthritis, Dickkopf-1 serum levels are correlated with parathy 2015 Jan OBJECTIVES: The objective of this study is to compare the serum levels of Dickkopf-1 (DKK1), a natural inhibitor of Wnt signalling, with parathyroid hormone (PTH) and bone involvement in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study includes 154 postmenopausal women with RA and 125 healthy controls. DKK1, 25OH vitamin D (25OHD), bone turnover markers, and PTH serum levels were measured by ELISA; lumbar spine and hip bone mineral density (BMD) and the erosion score were obtained. RESULTS: The RA patients and healthy controls were not significantly different in terms of age, body mass index, and 25OHD serum levels. The mean level of DKK1 and PTH were significantly higher in patients with RA than in healthy controls (172±68 [SD] vs. 96±55 pmoL/L, and 30±15 vs 22±11, respectively; p<0.0001). DKK1 serum levels were positively correlated with age (p<0.05) only in the healthy controls, while they were correlated with PTH serum levels only in the RA patients (p<0.0001). Among the RA patients, DKK1 levels adjusted for age, PTH and disease duration were significantly higher in patients with bone erosions (176 vs. 167 pmoL/L, respectively; p<0.05). DKK1 levels adjusted for age and PTH were negatively correlated with total hip BMD (p<0.05). In the RA patients not on treatment with bisphosphonates, DKK1 serum levels positively correlated with C-terminal telopeptides of type I collagene serum levels (p<0.05). CONCLUSIONS: In patients with RA, serum levels of DKK1 are significantly increased, correlate with PTH and are associated with increased risk of bone erosions and osteoporosis. However, this finding deserves confirmation in a larger and more selected population.
24437572 Therapeutic targets for rheumatoid arthritis: Progress and promises. 2014 Mar Recent therapeutic advancements in understanding of molecular and cellular mechanisms of rheumatoid arthritis (RA) have highlighted the strategies that aim to inhibit the harmful effects of up-regulated cytokines or other inflammatory mediators and to inhibit their associated signaling events. The utility of cytokine as therapeutic targets in RA has been unequivocally demonstrated by the success of tumor necrosis factor (TNF)-α blockade in clinical practice. Partial and non-responses to TNF-α blocking agents, however, together with the increasing clinical drive to remission induction, requires that further therapeutic targets be identified. Numerous proinflammatory mediators with their associated cell signaling events have now been demonstrated in RA, including interleukin (IL)-1 and IL-12 superfamilies. Continued efforts are ongoing to target IL-6, IL-15 and IL-17 in clinical trials with promising data emerging. In the present review, we focus on IL-7, IL-18, IL-32 and IL-10 family of cytokines (IL-19, IL-20 and IL-22) as they are implicated in contributing to the pathogenesis of RA, which could be targeted and offer new therapeutic options for RA therapy. Recent evidences also suggest that multiligand receptor for advanced glycation end products (RAGE), several adipokines and various components of immune system play a critical role in the pathophysiology of RA; therefore we have also highlighted them as therapeutic targets for RA therapy. Components of subcellular pathways, involve in nuclear transcription factor (NF)-κB, mitogen-activated protein kinases (MAPKs) and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway have also been discussed and offer several novel potential therapeutic opportunities for RA.
23640680 Hip score and disease activity correlation in patients with rheumatoid arthritis after tot 2013 Jul PURPOSE: The disease activity score including 28 joints (DAS28), the simplified disease activity index and the clinical disease activity index (CDAI) were developed in order to provide a quantifiable measure of rheumatoid arthritis (RA) activity. Although inflamed hip joints greatly impact activities of daily living (ADL) and walking ability, the hip joint was not included in the DAS28, SDAI or CDAI assessments. Although excellent clinical results have been reported for total hip arthroplasty (THA) in RA patients, correlations between disease activity and hip function in RA patients after THA remain unknown. METHODS: We analysed the effect of RA disease activity on a hip function score in an observational cohort of RA patients after THA. Twenty-five registered RA patients who had undergone THA (33 joints) were included. Hip function was recorded and RA disease activity was measured on the same day. The mean age of the patients was 65.17 years. They were followed up for a mean of 5.24 years after surgery. The mean duration of disease following RA diagnosis for this patient group was 19.47 years. The Japanese Orthopaedic Association (JOA) hip score was used as a clinical outcome measure for hip dysfunction. RA disease activity and health-related quality of life were measured using the DAS28, SDAI, CDAI and the modified health assessment questionnaire (MHAQ). RESULTS: The mean JOA score for hip function was 80.48 at the final follow-up. The mean DAS28-ESR, DAS28-CRP, SDAI, CDAI and MHAQ measuring RA disease activity levels were 3.38, 2.65, 9.59, 8.63 and 0.44, respectively, at the final follow-up. There was a significant negative correlation between the JOA hip score and all disease activity assessments observed after THA (DAS-ESR [P = 0.0067], DAS-CRP [P = 0.0008]), SDAI [P = 0.0034], CDAI [P = 0.0003]) and MHAQ [P = 0.0002]). CONCLUSION: We found significant negative correlations between JOA hip scores and all disease activity assessments in RA patients treated with THA.
23628683 [Fall risk and fracture. Associated factors for falls in patients with inflammatory polyar 2013 May Patients with rheumatoid arthritis (RA) have an increased risk of falls compared to healthy controls. Previous studies reported that the incidence of fractures in RA patients was mainly caused by falls. Some factors including tender and/or swollen joint counts, low levels of physical activity and history of falls are reported to be associated with falls in the patients with RA. Control of disease activity in the patients is essential to reduce the risk of falls and the burden of fracture. Moreover, potential interventions to prevent falls such as osteoporosis therapy and balance training are necessary for the patients.
24721160 Subclinical inflammation on MRI of hand and foot of anticitrullinated peptide antibody-neg 2014 Apr 10 INTRODUCTION: It is known that anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) has a preclinical phase. Whether this phase is also present in ACPA-negative RA is unknown. To determine this, we studied ACPA-negative arthralgia patients who were considered prone to progress to RA for local subclinical inflammation observed on hand and foot magnetic resonance imaging (MRI) scans. METHODS: We studied a total of 64 ACPA-negative patients without clinically detectable arthritis and with arthralgia of the small joints within the previous 1 year. Because of the character of the patients' symptoms, the rheumatologists considered these patients to be prone to progress to RA. For comparisons, we evaluated 19 healthy, symptom-free controls and 20 ACPA-negative RA patients, who were identified according to the 1987 American Rheumatism Association criteria. All participants underwent MRI of unilateral wrist, metacarpophalangeal and metatarsophalangeal joints. Synovitis and bone marrow oedema (BME) were scored according to the OMERACT rheumatoid arthritis magnetic resonance imaging scoring system, and the scores were summed to yield the 'MRI inflammation score'. Scores were compared between groups. Among the ACPA-negative arthralgia patients, MRI inflammation scores were related to C-reactive protein (CRP) levels and the tenderness of scanned joints. RESULTS: MRI inflammation scores increased progressively among the groups of controls and ACPA-negative arthralgia and RA patients (median scores = 0, 1 and 10, respectively; P < 0.001). The MRI inflammation scores of ACPA-negative arthralgia patients were significantly higher than those of controls (P = 0.018). In particular, the synovitis scores were higher in ACPA-negative arthralgia patients (P = 0.046). Among the ACPA-negative arthralgia patients, inflammation was observed predominantly in the wrist (53%). The synovitis scores were associated with CRP levels (P = 0.007) and joint tenderness (P = 0.026). Despite the limited follow-up duration, five patients developed clinically detectable arthritis. These five patients had higher scores for MRI inflammation (P = 0.001), synovitis (P = 0.002) and BME (P = 0.003) compared to the other patients. CONCLUSION: Subclinical synovitis was observed in the small joints of ACPA-negative arthralgia patients, and especially in patients whose conditions progressed to clinically detectable arthritis. This finding suggests the presence of a preclinical phase in ACPA-negative RA. Further longitudinal studies of these lesions and patients are required to confirm this hypothesis.
23378461 Anticitrullinated protein antibodies and rheumatoid factor fluctuate in early inflammatory 2013 Aug OBJECTIVE: In inflammatory arthritis, rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) are believed to be associated with more severe clinical outcomes. Our objective was to determine whether ACPA and RF remain stable in early inflammatory arthritis and whether their trajectories over time or baseline levels predicted clinical outcomes. METHODS: The study population consisted of patients enrolled in the Canadian Early Arthritis Cohort Study with baseline and at least 12-month followup values of RF and ACPA. Primary outcomes were Disease Activity Score (DAS) remission and the presence of erosions at 12 and 24 months. Other objectives included swollen joint count, Health Assessment Questionnaire score, and DAS. RESULTS: At baseline, 225/342 (66%) patients were ACPA-positive and 334/520 (64%) were RF-positive. At 24 months, 15/181 (8%) ACPA-positive patients became negative. A larger number of patients changed from ACPA-negative to positive: 13/123 (11%). For RF, fluctuations were more common: 67/240 (28%) reverted from positive to negative and 21/136 (18%) converted from negative to positive. RF and ACPA fluctuations did not predict disease outcomes. Patients who remained ACPA-positive throughout followup were more likely to have erosive disease (OR 3.86, 95% CI 1.68, 8.92). CONCLUSION: RF and ACPA have the potential to revert and convert during the early course of disease. Fluctuations in RF and ACPA were not associated with clinical outcomes.
25201689 PECAM-1 gene polymorphisms and soluble PECAM-1 level in rheumatoid arthritis and systemic 2014 Dec Genetic polymorphisms of platelet endothelial cell adhesion molecule-1 (PECAM-1) were found to play roles in atherosclerotic events. We determined PECAM-1 polymorphisms, soluble PECAM-1, and CD40L levels in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and evaluated their associations with clinical atherosclerotic complications. We included 100 RA patients, 81 SLE patients, and 94 healthy controls. The clinical features about the patients were obtained from medical records. Past cardiovascular complications were recorded. The most frequent gene polymorphisms of PECAM-1 were studied in our genetics laboratory. Soluble PECAM-1 and CD40L levels in serum were determined with ELISA. The frequencies of 373C (rs668) and 1688A (rs12953) alleles were higher in RA patients when compared to controls (p values, 0.028 and 0.016). RA and SLE patients had significantly higher allele frequencies for 2008A (rs1131012) when compared to controls (p values, 0.016 and 0.001). SLE patients had significantly more frequent AA genotype for rs1131012 polymorphism than RA patients and controls (p values, 0.007 and <0.001). Soluble PECAM-1 level was significantly higher in RA patients than in SLE patients and healthy controls (p values <0.001). Atherosclerotic complications were more frequent in SLE patients with AG genotype (rs12953) than those with AA genotype (p = 0.021). SLE patients with CC genotype (rs668) had a significantly lower frequency of atherosclerotic complications than those with CG genotype (p = 0.045). Nevertheless, in multivariate analysis, there was no association between genotype and atherosclerotic complications. We found associations between various PECAM-1 polymorphisms in RA and SLE; PECAM-1 and soluble CD40 ligand (sCD40L) levels were significantly higher in RA patients than in SLE and control groups. PECAM-1 polymorphisms in SLE were protective against atherosclerotic complications.
25238819 Linguistic validation and cultural adaptation of an English version of the evaluation of d 2014 Sep 20 BACKGROUND: To linguistically validate and culturally adapt the Evaluation of Daily Activity Questionnaire (EDAQ) for use in rheumatoid arthritis (RA) from Swedish to British English. The EDAQ is a patient reported outcome measure of daily activity ability. It includes 11 activity domains (Eating and Drinking; Personal Care; Dressing; Bathing; Cooking; Moving Indoors; House Cleaning; Laundry; Moving and Transfers; Communication; Moving Outdoors) and was developed for use in rheumatoid arthritis (RA). METHODS: The EDAQ was translated from Swedish to English using standard methods. Activity diaries, cognitive debriefing interviews and focus groups were completed with people with RA to: generate new culturally applicable items; identify important items in the Swedish version to retain in the English version; and develop the English EDAQ based on their views of content and layout. Content validity was established by linking the EDAQ to the International Classification of Functioning RA Core Set. RESULTS: The English EDAQ translation was harmonized with the Swedish version to ensure equivalence of meaning. Sixty-one people with RA participated. 156 activities were identified from 31 activity diaries and included in a draft English EDAQ. Following interviews (n = 20) and four focus groups, 138 activities were retained and three additional domains added (Gardening/Household Maintenance; Caring; and Leisure/Social Activities). Most ICF RA Core Set activities are in the EDAQ. CONCLUSIONS: The English EDAQ is a detailed self-report measure of ability in RA with good content validity.
25453596 Spleen and liver enlargement in a patient with rheumatoid arthritis. 2015 Jul We describe the case of a 51-year-old woman with a seropositive, erosive, and non-nodular rheumatoid arthritis of 15 year of evolution. The patient had poor compliance with medical visits and treatment. She came to the clinic with persistent pancytopenia and spleen and liver enlargement. Liver and bone marrow biopsies were carried out and amyloidosis, neoplasias and infections were ruled out. We discuss the differential diagnosis of pancytopenia and spleen and liver enlargement in a long-standing rheumatoid arthritis patient.
24507423 Diagnostic classification based on functional connectivity in chronic pain: model optimiza 2014 Mar RATIONALE AND OBJECTIVES: The combination of functional magnetic resonance imaging (fMRI) of the brain with multivariate pattern analysis (MVPA) has been proposed as a possible diagnostic tool. Goal of this investigation was to identify potential functional connectivity (FC) differences in the salience network (SN) and default mode network (DMN) between fibromyalgia syndrome (FMS), rheumatoid arthritis (RA), and controls (HC) and to evaluate the diagnostic applicability of derived pattern classification approaches. MATERIALS AND METHODS: The resting period during an fMRI examination was retrospectively analyzed in women with FMS (n = 17), RA (n = 16), and HC (n = 17). FC was calculated for SN and DMN subregions. Classification accuracies of discriminative MVPA models were evaluated with cross-validation: (1) inferential test of a single method, (2) explorative model optimization. RESULTS: No inferentially tested model was able to classify subjects with statistically significant accuracy. However, the diagnostic ability for the differential diagnostic problem exhibited a trend to significance (accuracy: 69.7%, P = .086). Optimized models in the explorative analysis reached accuracies up to 73.5% (FMS vs. HC), 78.8% (RA vs. HC), and 78.8% (FMS vs. RA) whereas other models performed at or below chance level. Comparable support vector machine approaches performed above average for all three problems. CONCLUSIONS: Observed accuracies are not sufficient to reliably differentiate between FMS and RA for diagnostic purposes. However, some indirect evidence in support of the feasibility of this approach is provided. This exploratory analysis constitutes a fundamental model optimization effort to be based on in further investigations.
24959711 Novel insights into the regulatory architecture of CD4+ T cells in rheumatoid arthritis. 2014 Rheumatoid arthritis (RA) is the most frequent autoimmune chronic inflammatory disease of the joints and it is characterized by the inflammation of the synovial membrane and the subsequent destruction of the joints. In RA, CD4+ T cells are the main drivers of disease initiation and the perpetuation of the damaging inflammatory process. To date, however, the genetic regulatory mechanisms of CD4+ T cells associated with RA etiology are poorly understood. The genome-wide analysis of expression quantitative trait loci (eQTL) in disease-relevant cell types is a recent genomic integration approach that is providing significant insights into the genetic regulatory mechanisms of many human pathologies. The objective of the present study was to analyze, for the first time, the genome-wide genetic regulatory mechanisms associated with the gene expression of CD4+ T cells in RA. Whole genome gene expression profiling of CD4+ T cells and the genome-wide genotyping (598,258 SNPs) of 29 RA patients with an active disease were performed. In order to avoid the excessive burden of multiple testing associated with genome-wide trans-eQTL analysis, we developed and implemented a novel systems genetics approach. Finally, we compared the genomic regulation pattern of CD4+ T cells in RA with the genomic regulation observed in reference lymphoblastoid cell lines (LCLs). We identified a genome-wide significant cis-eQTL associated with the expression of FAM66C gene (P = 6.51e-9). Using our new systems genetics approach we identified six statistically significant trans-eQTLs associated with the expression of KIAA0101 (P<7.4e-8) and BIRC5 (P = 5.35e-8) genes. Finally, comparing the genomic regulation profiles between RA CD4+ T cells and control LCLs we found 20 genes showing differential regulatory patterns between both cell types. The present genome-wide eQTL analysis has identified new genetic regulatory elements that are key to the activity of CD4+ T cells in RA.
23980356 [Significance of serum MMP-3, TIMP-1, and monocyte CD147 in rheumatoid arthritis patients 2013 Jun OBJECTIVE: To explore the clinical significance of serum matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1), and monocyte CD147 in rheumatoid arthritis (RA) patients of damp-heat Bi-syndrome (DHBS) and of cold-damp Bi-syndrome (CDBS). METHODS: The clinical data of 22 patients from inpatients and outpatients with RA were collected, and their peripheral blood was withdrawal. The disease activity scores [DAS28(4)] were assessed. The serum levels of MMP-3 and TIMP-1 were detected by double antibody sandwich enzyme linked immunosorbent assay (ELISA). The mean fluorescence intensity (MFI) and the expression percentage of CD147 on CD14+ monocytes were detected by flow cytometry. The difference of each index between RA patients of DHBS and RA patients of CDBS was analyzed. RESULTS: The level of serum MMP-3 and the MFI of CD147 on the monocyte surface were obviously higher in RA patients of DHBS than in those of CDBS and the normal control group (P < 0.05). The concentration of serum TIMP-1 was obviously higher in RA patients of DHBS than in those of the normal control group (P < 0.05), while there was no statistical difference between the two syndrome types. The percentage of CD147 expression was obviously lower in DHBS than in those of CDBS and the normal control group (P < 0.05). CONCLUSIONS: Increased serum MMP-3 level of RA patients of DHBS might result in destroy of joint cartilages and sclerotin. The significant increase of MFI and decreased expression percentage of monocyte CD147 might be the results of increased disease activity of RA and monocyte migration to the synovial membrane tissue.
23350658 Association of PTPN22 rs2476601 and EGFR rs17337023 Gene polymorphisms and rheumatoid arth 2013 Aug In this study we aimed to evaluate the possible association of PTPN22 rs2476601 as well as epidermal growth factor receptor (EGFR) rs17337023 gene polymorphism and rheumatoid arthritis (RA) in a sample of Iranian population. This case-control study was performed on 120 patients with RA and 120 healthy subjects. Genomic DNA was extracted from whole blood and PTPN22 rs2476601 and EGFR rs17337023 polymorphisms were determined using tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). The results showed that PTPN22 rs2476601 CT genotype as well as rs2476601 T allele was a risk factor for susceptibility to RA (OR=5.89 95%CI = 1.78-19.48, P = 0.004 and OR = 4.78, 95%CI = 1.59-14.35, P = 0.003, respectively). We also found that EGFR rs17337023 AT and rs17337023 TT genotypes were risk factor for susceptibility to RA (OR = 9.94 95%CI = 3.65-26.73, P < 0.001 and OR = 3.66, 95%CI = 1.46-9.15, P = 0.005, respectively). In addition the EGFR rs17337023 T allele was a risk for predisposition to RA (OR = 1.56, 95%CI=1.06-2.30, P = 0.030). In conclusion, we found an association between PTPN22 rs2476601 and EGFR rs17337023 polymorphisms and the risk of RA in a sample of Iranian population.
23644671 The risk of gastrointestinal perforations in patients with rheumatoid arthritis treated wi 2014 Jan OBJECTIVES: To evaluate the risk of gastrointestinal perforation (GIP) in subjects with rheumatoid arthritis (RA) treated with antitumour necrosis factor (anti-TNF) therapy compared with non-biological disease-modifying antirheumatic drugs (nbDMARDs). METHODS: Using data from the British Society for Rheumatology Biologics Register, we compared the incidence of GIPs between 11 881 anti-TNF-treated and 3393 nbDMARD-treated RA patients using Cox regression modelling. Hazard ratios (HRs) with confidence intervals (CI) were calculated. Adjustment was made for potential confounders including current steroid use. The study covered the time period between 2001 and 2011. RESULTS: There were 42 (upper 20, lower 22) GI perforations: five in the nbDMARD cohort and 37 in the anti-TNF cohort. After adjustment, treatment with TNF antagonists was associated with an HR of 1.6 (95% CI 0.4 to 6.0) for all GIPs, 2.7 (95% CI 0.4 to 18.1) for lower GIPs and 0.9 (95% CI 0.1 to 5.8) for upper GIPs. Current use of steroids was the single most important predictor of GI perforation with an adjusted HR of 2.9 (95% CI 1.5 to 5.4), but this risk was confined to lower GIPs (HR 8.0, 95% CI 2.6 to 24.1). CONCLUSIONS: We have not found a statistically significant association between anti-TNF treatment and the risk of GIP.