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ID PMID Title PublicationDate abstract
27476070 Omentin concentrations are independently associated with those of matrix metalloproteinase 2017 Jan Omentin is an adipokine that reportedly protects against cardiometabolic risk. We investigated the relationships between omentin concentrations and subclinical cardiovascular disease in rheumatoid arthritis (RA). Omentin concentrations were measured in 213 (104 black; 109 white) RA patients. Relationships of omentin levels with those of endothelial activation markers, ultrasound determined carotid intima-media thickness and plaque, and matrix metalloproteinase (MMP)-2, -3 and -9 that mediate altered plaque stability, were identified in confounder adjusted multivariate regression models. Omentin concentrations were inversely associated with MMP-3 levels [β = -364 (0.113), p = 0.002]. This relationship was influenced by population origin, RA activity and the erythrocyte sedimentation rate and joint deformity count (interaction p value = 0.009, 0.04, 0.04 and 0.007, respectively). Accordingly, the omentin-MMP-3 concentration relationship was reproduced in white [β (SE) = -0.450 (0.153), p = 0.0004)] but not black patients [β (SE) = -0.099 (0.195), p = 0.6)], in participants with disease remission or mild disease activity [β (SE) = -0.411 (0.139), p = 0.004] but not with moderate or severe RA activity [β (SE) = -0.286 (0.202), p = 0.2], and in those with a small [β (SE) = -0.534 (0.161), p = 0.001] but not large erythrocyte sedimentation rate [-0.212 (0.168), p = 0.2] and without [β (SE) = -0.554 (0.165), p = 0.0001] but not with large joint deformity counts [-0.110 (0.173), p = 0.5]. Omentin levels were unrelated to endothelial activation and atherosclerosis. Among patients with RA, a lack of plaque stabilizing effects by omentin may contribute to the reported link between severe disease and increased cardiovascular risk. The association between concentrations of omentin and MMP-3 is population specific in RA.
28742830 Regulatory effects of zinc on cadmium-induced cytotoxicity in chronic inflammation. 2017 OBJECTIVES: Zinc (Zn) has major effects on immune system activation while Cadmium (Cd) has anti-inflammatory and anti-proliferative effects in several chronic inflammatory contexts. The aim of this work was to investigate by which mechanisms Zn could compete with Cd and eventually counteract its deleterious effects. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as a model of chronic inflammation; osteoarthritis (OA) synoviocytes were used as control. METHODS: Cell/medium fractionation constants were analyzed for different metals by inductively-coupled-plasma mass-spectrometry by comparison to the 70Zn spike. Interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were used to mimic inflammation. Gene expression of ZIP-8 importer, metallothioneins-1 (MT-1s) and the ratio between metalloprotease-3 and the tissue inhibitor of metalloproteinases (MMP-3)/TIMP-1) were evaluated after pre-exposure to cytokines and Cd, with or without the addition of exogenous Zn (0.9 ppm). Cell viability was measured by neutral red assay and IL-6 production by ELISA. RESULTS: Synoviocytes selectively absorbed and retained Cd in comparison to Zn. Metal import increased with IL-17/TNF-α exposure, through the enhanced ZIP-8 expression. Zn did not modify ZIP-8 expression, while Cd reduced it (p<0.05). Zn induced a reduction of Cd-induced MT-1s expression, in particular of MT-1X (3-fold), and subsequently the final intra-cellular content of Cd. By reducing Cd accumulation in cells, Zn reversed Cd anti-proliferative and anti-inflammatory effects but preserved the low MMP-3/TIMP-1 ratio induced by Cd, which was enhanced by inflammatory conditions. CONCLUSION: Zinc counteracts the deleterious effect of Cd by reducing its import and accumulation in the cell, without the reactivation of destructive pathways such as MMPs.
28689441 Update of sarilumb to treat rheumatoid arthritis based on randomized clinical trials: a sy 2017 Aug Sarilumab is a human monoclonal antibody against Interleukin 6 α (IL-6α) receptor. Compared to tocilizumab, another IL-6 α receptor antibody, sarilumab has a different structure and higher affinity. Areas covered: In a systematic literature review, we examined all sarilumab randomized clinical trials (RCTs) in rheumatoid arthritis. The 6 reviewed RCTs included patients who were inadequate MTX, DMARD and/or TNFi responders. Sarilumab 150-200 mg every 2 weeks improved RA signs, symptoms, function and decreased radiological progression up to 52 weeks. The most common adverse events were infections and neutropenia, the latter of which will require careful observation in future trials. Examination of the effect of sero-positivity, disease duration, presence of erosions, use of previous biologic and comparisons to other biologics etc are still needed to complete understanding of this drug's profile. Long term studies, too, will be needed to assess long term tolerability Expert commentary: Results support the use of sarilumab to treat RA patients with inadequate response to MTX, other DMARDs and TNFis, although further studies are needed to fully assess its toxicity and understand the specific place of sarilumab in the RA armamentarium.
29362597 Health-related quality of life of rheumatic disease patients treated in a specialized IPS 2017 Oct PURPOSE: To compare Health-Related Quality of Life (HRQOL) profiles and their associated factors in people with rheumatoid arthritis (RA), spondyloarthritis (SpA), fibromyalgia (FM) and rheumatoid comorbidity treated in a specialized health center (SHC) in Medellin, Colombia. METHODS: A cross-sectional analytical study was performed with 93 RA patients, 30 SpA patients, 41 primary FM patients and 48 secondary FM patients with a concurrent diagnosis of RA or SpA. A demographic, socioeconomic, and clinical survey (the IPAQ, International Physical Activity Questionnaire) and the SF-36 survey validated in Medellin were administered. The statistical analyses were executed using SPSS 21.0 Results. Significant differences were found in all HRQOL dimensions among the patients, with physical performance perceived as the worst in the four groups. FM had the worst HRQOL profile, whereas the least affected group was SpA. Patients with RA and rheumatoid comorbidity shared similar HRQOL scores. The years of study, age and economic satisfaction variables were associated with the physical performance, vitality, social functioning, and mental health domains. CONCLUSION: The HRQOL profile was negative in patients with rheumatic diseases and lower in patients with FM. Additionally, variables or subgroups with greater deterioration were identified. This information will be useful for health activities and generate evidence in favor of incorporating HRQOL measurements into rheumatology services to complement clinical evaluations.
27333120 Inflammatory Arthritis Prevalence and Health Services Use in the First Nations and Non-Fir 2017 Apr OBJECTIVE: To estimate prevalence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic disease (PsD), and crystal-related arthritis and health care use for inflammatory arthritis in First Nations and non-First Nations patients in Alberta, Canada. METHODS: Population-based cohorts of adults with RA, AS, PsD, and crystal-related arthritis were defined, with First Nations determination by premium payer status, to estimate prevalence rates. Rates of outpatient primary care, specialist visits, and hospitalizations (all-cause, inflammatory-arthritis specific) were estimated. RESULTS: RA affected 3 times as many First Nations residents compared to non-First Nations residents (standardized rate ratio [SRR] 3.2, 95% confidence interval [95% CI] 2.9-3.4). AS and PsD were more prevalent in First Nations (AS 0.6 per 100 residents; SRR 2.7, 95% CI 2.3-3.2 and PsD 0.3 per 100 residents; SRR 1.5, 95% CI 1.3-1.9), whereas crystal-related arthritis was less prevalent (SRR 0.7, 95% CI 0.6-0.7). First Nations patients were more likely to have primary care visits (SRR 1.7, 95% CI 1.6-1.8) and less likely to have specialist visits (SRR 0.6, 95% CI 0.6-0.7) for RA relative to non-First Nations individuals. In PsD and crystal-related arthritis, First Nations people had higher rates of cause-specific hospitalizations. CONCLUSION: The estimated prevalence of RA, AS, and PsD was higher in the First Nations population, while crystal-related arthritis was less prevalent compared to the non-First Nations population. First Nations people were more likely to see primary care physicians and were less likely to see specialists for inflammatory arthritis care.
28271077 TMEM187-IRAK1 Polymorphisms Associated with Rheumatoid Arthritis Susceptibility in Tunisia 2017 Polymorphisms have been identified in the Xq28 locus as risk loci for rheumatoid arthritis (RA). Here, we investigated the association between three polymorphisms in the Xq28 region containing TMEM187 and IRAK1 (rs13397, rs1059703, and rs1059702) in two unstudied populations: Tunisian and French. The rs13397 G and rs1059703 T major alleles were significantly increased in RA patients (n = 408) compared with age-matched controls (n = 471) in both Tunisian and French women. These results were confirmed by a meta-analysis replication study including two independent Greek and Korean cohorts. The rs1059702 C major allele was significantly associated with RA, only with French women. In the French population, the GTC haplotype displayed a protective effect against RA, while the ATC, GCC, and GTT haplotypes conferred significant risk for RA. No association for these haplotypes was found in the Tunisian population. Our results replicated for the first time the association of the three Xq28 polymorphisms with RA risk in Tunisian and French populations and suggested that RA susceptibility is associated with TMEM187-IRAK1 polymorphisms in women. Our data further support the involvement of X chromosome in RA susceptibility and evidence ethnicities differences that might be explained by differences in the frequencies of SE HLA-DRB1 alleles between both populations.
27722971 Greek rheumatoid arthritis patients have elevated levels of antibodies against antigens fr 2017 Mar Patients with rheumatoid arthritis (RA) from different ethnic groups present elevated levels of antibodies against Proteus mirabilis. This finding implicates P. mirabilis in the development of RA. The aim of this study was to investigate the importance of P. mirabilis in the etiopathogenesis of RA in Greek RA patients. In this study, 63 patients with RA and 38 healthy controls were included. Class-specific antibodies IgM, IgG, and IgA against three human cross-reactive and non-cross-reactive synthetic peptides from P. mirabilis-hemolysin (HpmB), urease C (UreC), and urease F (UreF)-were performed in all subjects, using the ELISA method. RA patients had elevated levels of IgM, IgG, and IgA antibodies against HpmB and UreC Proteus peptide which are significantly different compared to healthy controls: p = 0.005, p < 0.001, and p = 0.003 and p = 0.007, p = 0.002, and p < 0.001, correspondingly. Also, elevated levels of IgM, IgG, and IgA antibodies against the UreF Proteus peptide-which are non-cross-reactive with human tissue antigens-were observed and their significant difference compared to healthy controls (p = 0.007, p < 0.001, p < 0.001). Anti-peptide antibodies in RA patients showed a significant correlation with rheumatoid factors (Rf), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), especially when patients were divided into subgroups according to the receiving treatment. Greek RA patients present elevated levels of antibodies against P. mirabilis antigenic epitopes, such as in North European populations, albeit Greek RA patients presenting the cross-reaction antigen in a low percentage. These results indicate that P. mirabilis through the molecular mimicry mechanism leads to inflammation and damage of the joints in RA.
28921409 The Duality of Economic Issues With Medication Non-adherence in Patients With Inflammatory 2017 Sep 18 PURPOSE OF REVIEW: In this review, we synthesize current data on non-adherence across inflammatory arthritides and explore (1) the effects of economic factors on non-adherence and (2) the impacts of non-adherence on economic outcomes. RECENT FINDINGS: Recent evidence demonstrates medication non-adherence rates as high as 74% in ankylosing spondylitis (AS), 90% in gout, 50% in psoriatic arthritis (PsA), 75% in systemic lupus erythematosus (SLE), and 82% in rheumatoid arthritis (RA). The effects of socioeconomic factors have been studied most in RA and SLE but with inconsistent findings. Nonetheless, the evidence points to having prescription coverage and costs of treatment as important factors in RA and education as an important factor in SLE. Limited data in AS and gout, and no studies of the effects of socioeconomic factors in PsA, show knowledge gaps for future research. Finally, there is a dearth of data with respect to the impacts of non-adherence on economic outcomes.
27239678 Determination of Serum Trace Elements (Zn, Cu, and Fe) in Pakistani Patients with Rheumato 2017 Jan Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, which mainly involves the joints. RA is prevalent worldwide with increasing prevalence in elderly people. The mechanism of RA pathogenesis is still undefined, and it is interplaying between genetic susceptibility and environmental factors. Although risk factors for RA are not fully established, various studies have focused on the role of trace elements in association with RA. Trace elements act as co-factors for most of the enzymes, and their deficiency is associated with many untoward effects on human health. The homeostatic alterations in the metabolism of trace elements may partly be due to inflammatory response in RA. The objective of the present study was to determine the serum concentrations and correlation of zinc, copper, and iron in RA patients and healthy controls. The study comprised of 61 RA patients and 61 age- and sex-related healthy individuals of Pakistani population. Serum levels of Zn, Cu, and Fe were measured in all the participants by atomic absorption spectrophotometer. Serum Zn and Fe were significantly reduced in the RA patients than those in the healthy controls. Serum Cu concentrations were found elevated in the RA patients. Correlation studies of trace elements determine that there was negative correlation between Zn and Cu in the RA patients and no correlation in the control group. It is very important to explore the deficiency of essential trace metals in biological samples of the RA patients in different populations which may be helpful for diagnosis and supplementary management of rheumatoid arthritis patients.
28802150 MiR-let-7a regulates anti-citrullinated protein antibody-induced macrophage activation and 2017 Oct Anti-citrullinated protein antibodies (ACPAs) are a key serological marker of rheumatoid arthritis (RA). To investigate whether miR-let7a downregulated ACPA-induced macrophage activation and arthritis, miR-let7a levels were assessed in the synovial fluid from patients with RA or osteoarthritis (OA). In addition, expression of the pro-inflammatory genes HMGA2, PI3K, and IRF5 was examined in ACPA-induced macrophages and a collagen antibody-induced mouse model of arthritis. As expected, miR-let7a expression in synovial fluid macrophages was substantially lower in patients with RA than in those with OA. Moreover, ACPAs treatment (160IU/mL) suppressed miR-let7a expression in macrophages isolated from patients with RA. Mechanistic studies revealed that miR-let7a directly targets HMGA2 to suppress ACPA-induced IRF5 expression through PI3K in macrophages. Further, miR-let7a expression was markedly decreased in swollen ankle tissue and splenocytes isolated from arthritic mice, whereas HMGA2, PI3K, and IRF5 expression positively correlated with disease severity. However, injection miR-let7a agomir was unable to mitigate the development of experimental arthritis in model mice. Collectively, these data demonstrated that miR-let7a directly targets HMGA2 to downregulate ACPAs-induced macrophage activation, and correlated with experimental RA severity.
28747604 [Methotrexate-associated lymphoproliferative disorder]. 2017 Methotrexate-associated lymphproliferative disorder (MTX-LPD) is a rare but critical complication developing in patients treated with methotrexate. Now that methotrexate is an anchor drug in the management of rheumatoid arthritis and become commonly used, MTX-LPD cases have increased. Many things has been unclear such as incidence, demographic characters, and risk factors. However, as the researches increased, several interesting topics has been demonstrated like associations with Epsteiin-Barr virus and with cell-mediated immunity. This report reviews newly the latest findings and future challenges on MTX-LPD.
28968858 Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis-a proo 2017 Nov 1 OBJECTIVES: RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. METHODS: We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0-6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6-12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome. RESULTS: Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0-6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6-12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016). CONCLUSION: Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states. TRAIL REGISTRATION: EudraCT, https://www.clinicaltrialsregister.eu, 2010-020738-24; ISRCTN registry, https://www.isrctn.com, 28955701.
28448409 Assessing Synovitis and Bone Erosion With Apparent Diffusion Coefficient in Early Stage of 2017 Sep/Oct PURPOSE: The aim of this study was to assess the value of apparent diffusion coefficient (ADC) in distinguishing synovitis from joint fluid and bone erosion from cysts. METHODS: Twenty-eight patients with suspected rheumatoid arthritis underwent diffusion-weighted imaging and pre- and post-contrast-enhanced magnetic resonance imaging. The mean ADC values were compared between synovitis and joint effusion and between bone erosion and cyst. RESULTS: Mean ADC value of synovitis was significantly lower than that of the joint effusion (2.6 ± 0.37 × 10 vs 1.63 ± 0.37 × 10 mm/s, P < 0.001; cutoff value 2.10 × 10 mm/s). Mean ADC value of bone erosion was significantly lower than that of the cysts (1.61 ± 0.39 × 10 vs 2.39 ± 0.34 × 10 mm/s, P < 0.001; cutoff value 2.04 × 10 mm/s). CONCLUSION: Apparent diffusion coefficient can be used in differentiating between synovitis and joint effusion and between bone erosion and cysts.
28594905 Comparative risk of hospitalized infection between biological agents in rheumatoid arthrit 2017 OBJECTIVE: Knowing the risk of hospitalized infection associated with individual biological agents is an important factor in selecting the best treatment option for patients with rheumatoid arthritis (RA). This study examined the comparative risk of hospitalized infection between biological agents in a routine care setting. METHODS: We used data for all RA patients who had first begun biological therapy at rheumatology divisions of participating community hospitals in Japan between January 2009 and December 2014. New treatment episodes with etanercept, infliximab, adalimumab, abatacept, or tocilizumab were included. Patients were allowed to contribute multiple treatment episodes with different biological agents. Incidence rates (IRs) of hospitalized infection during the first year of follow-up were examined. Cox regression analysis was used to calculate hazard ratios (HRs) for overall hospitalized infection and for pulmonary hospitalized infection, adjusting for possible confounders. RESULTS: A total of 1596 new treatment episodes were identified. The incidence of overall hospitalized infection during the first year was 86 with 1239 person-years (PYs), yielding a crude IR of 6.9 per 100 PYs (95% confidence interval [CI], 5.6-8.6). After correction for confounders, no significant difference in risk of hospitalized infection was observed between treatment groups: adjusted HRs (95% CI) were 1.54 (0.78-3.04) for infliximab, 1.72 (0.88-3.34) for adalimumab, 1.11 (0.55-2.21) for abatacept, and 1.02 (0.55-1.87) for tocilizumab compared with etanercept. Patient-specific factors such as age, RA functional class, body mass index (BMI), prednisolone use, and chronic lung disease contributed more to the risk of hospitalized infection than specific biological agents. The incidence of pulmonary hospitalized infection was 50 and a crude IR of 4.0 per 100 PYs (95% CI, 3.1-5.3). After adjustment for confounders, adalimumab had a significantly higher HR for pulmonary hospitalized infection compared with tocilizumab: an adjusted HR (95% CI) was 4.43 (1.72-11.37) for adalimumab. BMI, prednisolone use, diabetes mellitus, and chronic lung disease were also significant factors associated with the risk of pulmonary hospitalized infection. CONCLUSIONS: The magnitude of the risk of overall hospitalized infection was not determined by the type of biological agents, and patient-specific risk factors had more impact on the risk of hospitalized infection. For pulmonary hospitalized infections, the use of adalimumab was significantly associated with a greater risk of this complication than tocilizumab use.
28556506 Dissociated Agonist of Glucocorticoid Receptor or Prednisone for Active Rheumatoid Arthrit 2017 Jul Fosdagrocorat (PF-04171327), a dissociated agonist of the glucocorticoid receptor, has potent anti-inflammatory activity in patients with rheumatoid arthritis with reduced adverse effects on bone health. To identify fosdagrocorat doses with bone formation marker changes similar to prednisone 5 mg, we characterized treatment-related changes in amino-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC) with fosdagrocorat (1, 5, 10, or 15 mg) and prednisone (5 or 10 mg) in a phase II randomized trial (N = 323). The time course of markers utilized a mixed-effects longitudinal kinetic-pharmacodynamic model. Median predicted changes from baseline at week 8 with fosdagrocorat 5, 10, and 15 mg were -18, -22, and -22% (P1NP), and -7, -13, and -17% (OC), respectively. Changes with prednisone 5 and 10 mg were -15% and -18% (P1NP) and -10% and -17% (OC). The probability of fosdagrocorat doses up to 15 mg being noninferior to prednisone 5 mg for P1NP and OC changes was >90%.
28799033 Isolated atrophy of the abductor digiti quinti in patients with rheumatoid arthritis. 2017 Dec OBJECTIVE: We aim to discuss the association of isolated atrophy of the abductor digiti quinti muscle in patients with rheumatoid arthritis as well as review the anatomy and imaging findings of this condition on MRI. MATERIALS AND METHODS: A consecutive series of 55 patients diagnosed with rheumatoid arthritis according to the 2010 ACR/EULAR classification criteria were recruited. MRI of the clinically dominant feet was performed using a 1.5-T scanner. RESULTS: The study population was predominantly female (94.5%), and the age range was 31-79 years (mean 57.5 ± 11). A total of 55 ankles were examined by MRI, and 20 patients (36.3%), all females, showed abductor digiti quinti denervation signs. Seven patients demonstrated severe fatty atrophy of the abductor digiti quinti, corresponding to Goutallier grade 4, 2 patients showed moderate fatty atrophy (Goutallier grade 3), and the remaining 11 patients showed less than 50% fatty atrophy, corresponding to a Goutallier grade 2. Substantial agreement was found for both intra- and interobserver agreement regarding the Goutallier grading system. CONCLUSION: Prevalence of signs of abductor digiti quinti denervation on MRI was high in the studied population, suggesting that rheumatoid arthritis may be associated with inferior calcaneal nerve compression.
28913891 Venous thromboembolism and risk of cancer in patients with rheumatoid arthritis. 2017 Dec Essentials Can venous thromboembolism (VTE) in rheumatoid arthritis (RA) patients be marker of cancer? RA patients with VTE and comparison cohorts from population-based registries were compared. Increased risk of cancer in RA patients with VTE during the first year of VTE was observed. Risk of cancer in RA patients was increased also during the longer period following VTE. SUMMARY: Background It is unknown whether venous thromboembolism (VTE) in rheumatoid arthritis (RA) patients can be a marker of occult cancer. Objectives To examine risk of cancer subsequent to VTE among RA patients compared with risk of cancer in an RA cohort without VTE and in a general population without RA and without VTE. Patients/Methods All RA patients with a first-time diagnosis of VTE (index date) during 1978-2013 and comparison cohorts were identified from population-based registries in Denmark. Results We identified three cohorts: 2497 RA patients with VTE, 11 672 RA patients without VTE and 12 730 persons from the general population. The cumulative incidence of cancer within the first year of the index date was 3.2% among RA with VTE, 2.2% among RA without VTE, and 2.0% in the general population cohort. Incidence rate ratios (IRRs) were 1.79 (95% confidence interval [CI], 1.37-2.33) for RA patients with VTE vs. RA patients without VTE and 2.12 (95% CI, 1.63-2.76) for RA patients with VTE vs. the general population. The IRR of cancer at > 1 to 36 years from the index date among RA patients with VTE was 1.16 (95% CI, 1.00-1.34) compared with the RA patients without VTE and 1.33 (95% CI, 1.15-1.53) compared with the general population. Conclusions We found an increased risk of cancer in RA patients with VTE during the first year following VTE and also during the longer follow-up period. Thus, VTE may not only be a result of inflammation and immunological dysfunctions associated with RA, but may also be a marker for occult cancer.
27974097 In early inflammatory polyarthritis more intensive management according to the 2010 ACR/EU 2017 May OBJECTIVES: The aim of this study was to compare the 12-month probability of remission in early inflammatory arthritis with a milder treatment based on the 1987 criteria or a more intensive protocol based on the 2010 criteria. METHODS: Patients with rheumatoid arthritis (RA) or undifferentiated arthritis (UA) (2005-2012) were included. Before October 2010, patients fulfilling the 1987 criteria received methotrexate (MTX) and possibly low-dose prednisone, while UA hydroxychloroquine (HCQ) (1987-driven cohort). From October 2010, patients fulfilling the 2010 criteria received higher dose MTX and low-dose prednisone, while UA HCQ (2010-driven cohort). Treatment was increased to achieve DAS28 low disease activity. Clinical remission, defined by DAS28, was evaluated at subsequent visits in the whole population. Hazard ratios (HR) adjusted for age, sex, baseline DAS28, symptoms duration, MTX dose and prednisone were calculated by Cox regression. RESULTS: 677 patients were included (468 in 1987-driven cohort, 209 in 2010-driven cohort), with no significant differences in age, gender, autoantibodies and pain. The 2010-driven cohort had significantly fewer tender and swollen joints, lower acute phase reactants, DAS28 and HAQ and achieved more frequently remission even when the analysis was adjusted for all confounders (adjusted HR (95% CI) 1.73 (1.34, 2.22)) and limited to per protocol patients (adjusted HR (95%CI) 1.49 (1.11, 2.02). CONCLUSIONS: Treating patients with early arthritis according to a more intensive protocol leads to higher remission rate. The results of this study support the use of a strategy led by the 2010 criteria with more intensive treatment strategies in the management of early arthritis.
27585642 Genome-wide DNA methylation patterns in CD4+ T cells from Chinese Han patients with rheuma 2017 May INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Recent evidence indicated the epigenetic changes may contribute to the pathogenesis of RA. METHOD: To understand the extent and nature of dysregulated DNA methylation in RA CD4T cells, we performed a genome-wide DNA methylation study in CD4 + T cells in 12 RA patients compared to 12 matched normal healthy controls. Cytosine methylation status was quantified with Illumina methylation 450K microarray. RESULT: The DNA methylation profiling showed 383 hyper- and 785 hypo-methylated genes in the CD4 + T cells of the RA patients (p < 3.4 × 10(-7)). Gene ontology analysis indicated transcript alternative splicing and protein modification mediated by DNA methylation might play an important role in the pathogenesis of RA. In addition, the result showed that human leukocyte antigen (HLA) region including HLA-DRB6, HLA-DQA1 and HLA-E was frequently hypomethylated, but HLA-DQB1 hypermethylated in CpG island region and hypomethylated in CpG shelf region in RA patients. Outside the MHC region, HDAC4, NXN, TBCD and TMEM61 were the most hypermethylated genes, while ITIH3, TCN2, PRDM16, SLC1A5 and GALNT9 are the most hypomethylated genes. CONCLUSION: Genome-wide DNA methylation profile revealed significant DNA methylation change in CD4 + T cells from patients with RA.
28669029 Slc11a1 (Nramp-1) gene modulates immune-inflammation genes in macrophages during pristane- 2017 Nov OBJECTIVE AND DESIGN: Pristane-induced arthritis (PIA) in AIRmax mice homozygous for Slc11a1 R and S alleles was used to characterize the influence of Slc11a1 gene polymorphism on immune responses during disease manifestation. Previous reports demonstrated that the presence of the Slc11a1 S allele increased the incidence and severity of PIA in AIRmax (SS) , suggesting that this gene could interact with inflammatory loci to modulate PIA. We investigated the effects of Slc11a1 alleles on the activation of phagocytes during PIA. TREATMENT: Mice were injected intraperitoneally with two doses of 0.5 mL of mineral oil pristane at 60-day intervals. Arthritis development was accompanied for 180 days. RESULTS: AIRmax (SS) mice showed differential peritoneal macrophage gene expression profiles during PIA, with higher expression and production of H(2)O(2), NO, IL-1β, IL-6, TNF-α, and several chemokines. The presence of the Slc11a1 R allele, on the other hand, diminished the intensity of macrophage activation, restricting arthritis development. CONCLUSION: Our data demonstrated the fine-tuning roles of Slc11a1 alleles modulating macrophage activation, and consequent PIA susceptibility, in those mouse lines.