Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
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27329782 | RAACFDb: Rheumatoid arthritis ayurvedic classical formulations database. | 2017 Feb 2 | ETHNOPHARMACOLOGICAL RELEVANCE: In the past years, the treatment of rheumatoid arthritis (RA) has undergone remarkable changes in all therapeutic modes. The present newfangled care in clinical research is to determine and to pick a new track for better treatment options for RA. Recent ethnopharmacological investigations revealed that traditional herbal remedies are the most preferred modality of complementary and alternative medicine (CAM). However, several ayurvedic modes of treatments and formulations for RA are not much studied and documented from Indian traditional system of medicine. Therefore, this directed us to develop an integrated database, RAACFDb (acronym: Rheumatoid Arthritis Ayurvedic Classical Formulations Database) by consolidating data from the repository of Vedic Samhita - The Ayurveda to retrieve the available formulations information easily. MATERIALS AND METHODS: Literature data was gathered using several search engines and from ayurvedic practitioners for loading information in the database. In order to represent the collected information about classical ayurvedic formulations, an integrated database is constructed and implemented on a MySQL and PHP back-end. RESULTS: The database is supported by describing all the ayurvedic classical formulations for the treatment rheumatoid arthritis. It includes composition, usage, plant parts used, active ingredients present in the composition and their structures. CONCLUSION: The prime objective is to locate ayurvedic formulations proven to be quite successful and highly effective among the patients with reduced side effects. The database (freely available at www.beta.vit.ac.in/raacfdb/index.html) hopefully enables easy access for clinical researchers and students to discover novel leads with reduced side effects. | |
27124044 | Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rh | 2016 Apr | To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice.We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS) > 3.0 U. We also divided the cohort into 2 groups based on disease duration (<3 vs ≥3 years) and performed a subgroup analysis.CRRP was found in 10.3% of the patients. A multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: CRP at baseline (0.30 mg/dL increase, 95% confidence interval [CI] 1.01-1.11), time-integrated Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) during the 1 year postbaseline (12.4-unit increase, 95%CI 1.17-2.59), RA typical erosion at baseline (95%CI 1.56-21.1), and the introduction of bDMARDs (95%CI 0.06-0.38). The subgroup analysis revealed that time-integrated DAS28-ESR is not a predictor whereas the introduction of bDMARDs is a significant protective factor for CRRP in RA patients with disease duration <3 years.We identified factors that could be used to predict the development of CRRP in RA patients treated with DMARDs. These variables appear to be different based on the RA patients' disease durations. | |
25280085 | Pharmacokinetic-pharmacodynamic modeling of fostamatinib efficacy on ACR20 to support dose | 2015 Mar | R788 (fostamatinib) is an oral prodrug that is rapidly converted into a relatively selective spleen tyrosine kinase (SYK) inhibitor R406, evaluated for the treatment of rheumatoid arthritis (RA). This analysis aimed at developing a pharmacodynamic model for efficacy using pooled ACR20 data from two phase II studies in patients with rheumatoid arthritis (TASKi1 and TASKi2), describing the effect of fostamatinib as a function of fostamatinib exposure (dose, R406 plasma concentration) and other explanatory variables. The exposure-response relationship of fostamatinib was implemented into a continuous time Markov model describing the time course of transition probabilities between the three possible states of ACR20 non-responder, responder, and dropout at each visit. The probability of transition to the ACR20 response state was linearly (at the rate constant level) related to average R406 plasma concentrations and the onset of this drug effect was fast. Further, increases of fostamatinib dose resulted in increased dropout and subsequent loss of efficacy. This analysis provided an increased understanding of the exposure-response relationship, and provided support for fostamatinib 100 mg BID an appropriate dose regimen for further clinical evaluation. | |
27311181 | [New assessment method in rheumatoid arthritis]. | 2016 Jun | To assess disease activity in rheumatoid arthritis (RA), several composite measures have been used. However, more objective indices have been desired due to subjectivity in conventional indices. The Multi-Biomarker Disease Activity(MBDA) score is a novel serum testing based disease activity score ranging 1-100, derived from pre-specified algorithms in combination with 12 biomarkers. The MBDA score not only reflects disease activity in RA, but also is predictive for radiographic progression and risk of flare after drug reduction. Here we review usefulness of the MBDA score in RA. | |
25593225 | Assessment of fatigue in rheumatoid arthritis: a psychometric comparison of single-item, m | 2015 Mar | OBJECTIVE: To compare the psychometric functioning of multidimensional disease-specific, multiitem generic, and single-item measures of fatigue in patients with rheumatoid arthritis (RA). METHODS: Confirmatory factor analysis (CFA) and longitudinal item response theory (IRT) modeling were used to evaluate the measurement structure and local reliability of the Bristol RA Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ), the Medical Outcomes Study Short Form-36 (SF-36) vitality scale, and the BRAF Numerical Rating Scales (BRAF-NRS) in a sample of 588 patients with RA. RESULTS: A 1-factor CFA model yielded a similar fit to a 5-factor model with subscale-specific dimensions, and the items from the different instruments adequately fit the IRT model, suggesting essential unidimensionality in measurement. The SF-36 vitality scale outperformed the BRAF-MDQ at lower levels of fatigue, but was less precise at moderate to higher levels of fatigue. At these levels of fatigue, the living, cognition, and emotion subscales of the BRAF-MDQ provide additional precision. The BRAF-NRS showed a limited measurement range with its highest precision centered on average levels of fatigue. CONCLUSION: The different instruments appear to access a common underlying domain of fatigue severity, but differ considerably in their measurement precision along the continuum. The SF-36 vitality scale can be used to measure fatigue severity in samples with relatively mild fatigue. For samples expected to have higher levels of fatigue, the multidimensional BRAF-MDQ appears to be a better choice. The BRAF-NRS are not recommended if precise assessment is required, for instance in longitudinal settings. | |
26834220 | Myeloid-related Protein 8/14 Levels in Rheumatoid Arthritis: Marker of Disease Activity an | 2016 Apr | OBJECTIVE: Myeloid-related proteins (MRP) 8/14 belong to a family of calcium-binding proteins produced by myeloid cells. Baseline serum levels of MRP8/14 have been shown to predict response to biologicals in rheumatoid arthritis (RA). Because methotrexate (MTX) is the first-line therapy in RA, we studied whether MRP8/14 levels can predict response to MTX. METHODS: Patients with active RA disease who were naive to disease-modifying antirheumatic drugs were enrolled. All patients were treated with MTX only, to a maximum of 25 mg/week or the maximal tolerated dose. At 4 months, the European League Against Rheumatism response was assessed. All patients who needed rescue therapy after 2 months or who did not respond at 4 months were classified as nonresponders. RESULTS: Ninety patients were enrolled, of whom 3 discontinued MTX within 4-6 weeks, so 87 patients were analyzed [74 women, median (interquartile range; IQR) for the Disease Activity Score at 28 joints (DAS28) was 4.43 (4.1-5.1)]. The median (IQR) serum MRP8/14 level at baseline was 19.95 µg/ml (11.49-39.06). The serum MRP8/14 had good correlation with DAS28-C-reactive protein (CRP; r = 0.35, p = 0.001). The MRP8/14 levels fell significantly after 4 months of treatment (10.28 µg/ml, 5.95-16.05, p < 0.001). Among 87 patients, 69 were responders. The median (IQR) baseline level of MRP8/14 was higher among responders compared with nonresponders: 23.99 µg/ml (15.39-42.75) versus 9.58 µg/ml (6.11-24.93, p = 0.00250). The levels declined in the responders, from 23.99 µg/ml (15.39-42.75) to 10.41 µg/ml (5.83-15.61, p < 0.001), but not in the nonresponders, from 9.58 µg/ml (6.11-24.93) to 9.19 µg/ml (7.74-21.96, p = 0.687). Receiver-operation characteristic analysis showed that MRP8/14 was a better predictor of response than CRP and erythrocyte sedimentation rate, especially with early disease onset (< 1-yr duration). CONCLUSION: MRP8/14 is a good marker of disease activity in RA, and higher levels predict response to MTX. | |
27553213 | Novel algorithms for the pragmatic use of ultrasound in the management of patients with rh | 2016 Nov | The absence of specific guidance on how to use ultrasound (US) to diagnose and manage patients with inflammatory arthritis, especially with rheumatoid arthritis (RA) has hindered the optimal utilisation of US in clinical practice, potentially limiting its benefits for patient outcomes. In view of this, a group of musculoskeletal US experts formed a working group to consider how this unmet need could be satisfied and to produce guidance (additional to European League against Rheumatism (EULAR) imaging recommendations) to support clinicians in their daily clinical work. This paper describes this process and its outcome, namely five novel algorithms, which identify when US could be used. They are designed to aid diagnosis, to inform assessment of treatment response/disease monitoring and to evaluate stable disease state or remission in patients with suspected or established RA, by providing a pragmatic template for using US at certain time points of the RA management. A research agenda has also been defined for answering unmet clinical needs. | |
27903508 | The patient perspective on absence of disease activity in rheumatoid arthritis: a survey t | 2017 May | BACKGROUND: Guidelines suggest treatment in rheumatoid arthritis (RA) to target remission, in close consultation with the patient. Our recent qualitative study of the patients' perspective on remission in RA identified 26 domains. The current study aimed to identify a short list of the most important aspects to inform future research. METHODS: Patients with RA from the Netherlands, the UK, Austria, Denmark, France and the USA completed a survey that contained all domains identified in our qualitative study. They rated domains for importance ('not important', 'important' or 'essential' to characterise a period of remission) and if important or essential, whether this domain needs to be 'less', 'almost gone' or 'gone' to reflect remission. Respondents were also asked to determine their personal top 3 most important/essential domains. Frequency of specific domains in the top 3 was calculated, and domains were sorted on the percentage of patients that evaluated a particular domain as 'essential'. RESULTS: Of 274 respondents, 75% were female, mean (SD) age 57(13) years, disease duration 12(9) years. The top 3 were as follows: pain (67%), fatigue (33%) and independence (19%); domains most frequently rated as 'essential' were as follows: pain (60%), being mobile (52%), physical function (51%), being independent (47%) and fatigue (41%). Pain needed to be less (13%), almost gone (42%) or gone (45%) to reflect remission. Similar patterns were seen for fatigue, independence, mobility and physical functioning. CONCLUSION: Patients identified pain, fatigue and independence as the most important domains of RA disease activity that need to be improved to reflect remission. | |
24119062 | Potential of a 70Â kDa IL-10-like factor in synovial fluid from rheumatoid arthritis patie | 2016 Feb | AIM: To elucidate the role of polymorphonuclear leukocytes (PMNs) in joint destruction during the inflammatory process in rheumatoid arthritis (RA) as related to superoxide generation. METHODS: Superoxide generation by human peripheral PMNs was measured by using a water-soluble formazan dye, 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt, under PMN stimulation with N-formylmethionyl-leucyl-phenylalanine (fMLP) and cytochalasin B. Factors in synovial fluids (SF) from RA patients that may augment PMN superoxide generation were characterized via high-performance liquid chromatography and isoelectric focusing. RESULTS: The formazan dye allowed measurement of superoxide generated in the xanthine-xanthine oxidase system and by PMNs stimulated by cytochalasin B and fMLP in the presence of the intermediate electron transporter phenazine methosulfate. By using chromatography and electrophoresis, an RA-SF protein with an apparent molecular size of 70Â kDa and an isoelectric point of 8.3 was isolated and was demonstrated to increase superoxide generation by PMNs. The factor was heat-labile and susceptible to protease treatment. This enhancing activity of the factor was absorbed by human PMNs and was somewhat immunoadsorbed with a specific monoclonal antibody against interleukin (IL)-10. CONCLUSION: The 70-kDa protein factor in RA-SF increased superoxide generation by human PMNs, which suggests the possibility of its being related to IL-10. This factor may have a pathological role in RA joint destruction caused by PMNs and coinciding with rheumatoid inflammation, which suggests that PMNs, via superoxide generation, play an important role in RA joint destruction. IL-10 therefore likely has biological activity toward PMNs during synovial inflammatory chain reactions in RA. | |
27029006 | A Personalized Approach to Biological Therapy Using Prediction of Clinical Response Based | 2016 | OBJECTIVES: Measurement of MRP8/14 serum levels has shown potential in predicting clinical response to different biological agents in rheumatoid arthritis (RA). We aimed to develop a treatment algorithm based on a prediction score using MRP8/14 measurements and clinical parameters predictive for response to different biological agents. METHODS: Baseline serum levels of MRP8/14 were measured in 170 patients starting treatment with infliximab, adalimumab or rituximab. We used logistic regression analysis to develop a predictive score for clinical response at 16 weeks. MRP8/14 levels along with clinical variables at baseline were investigated. We also investigated how the predictive effect of MRP8/14 was modified by drug type. A treatment algorithm was developed based on categorizing the expected response per drug type as high, intermediate or low for each patient and optimal treatment was defined. Finally, we present the utility of using this treatment algorithm in clinical practice. RESULTS: The probability of response increased with higher baseline MRP8/14 complex levels (OR = 1.39), differentially between the TNF-blockers and rituximab (OR of interaction term = 0.78), and also increased with higher DAS28 at baseline (OR = 1.28). Rheumatoid factor positivity, functional disability (a higher HAQ), and previous use of a TNF-inhibitor decreased the probability of response. Based on the treatment algorithm 80 patients would have been recommended for anti-TNF treatment, 8 for rituximab, 13 for another biological treatment (other than TNFi or rituximab) and for 69 no recommendation was made. The predicted response rates matched the observed response in the cohort well. On group level the predicted response based on the algorithm resulted in a modest 10% higher response rate in our cohort with much higher differences in response probability in individual patients treated contrary to treatment recommendation. CONCLUSIONS: Prediction of response using MRP8/14 levels along with clinical predictors has potential in personalizing treatment for RA patients starting biological anti-rheumatic treatment, and might increase cost-effectiveness. | |
25981462 | Mass cytometry as a platform for the discovery of cellular biomarkers to guide effective r | 2015 May 18 | The development of biomarkers for autoimmune diseases has been hampered by a lack of understanding of disease etiopathogenesis and of the mechanisms underlying the induction and maintenance of inflammation, which involves complex activation dynamics of diverse cell types. The heterogeneous nature and suboptimal clinical response to treatment observed in many autoimmune syndromes highlight the need to develop improved strategies to predict patient outcome to therapy and personalize patient care. Mass cytometry, using CyTOF®, is an advanced technology that facilitates multiparametric, phenotypic analysis of immune cells at single-cell resolution. In this review, we outline the capabilities of mass cytometry and illustrate the potential of this technology to enhance the discovery of cellular biomarkers for rheumatoid arthritis, a prototypical autoimmune disease. | |
26097231 | Cause-Specific Mortality in Male US Veterans With Rheumatoid Arthritis. | 2016 Jan | OBJECTIVE: There has been limited investigation into cause-specific mortality and the associated risk factors in men with rheumatoid arthritis (RA). We investigated all-cause and cause-specific mortality in men with RA, examining determinants of survival. METHODS: Men from a longitudinal RA registry were followed from enrollment until death or through 2013. Vital status and cause of death were determined using the National Death Index. Crude mortality rates and standardized mortality ratios (SMRs) were calculated for all-cause, cardiovascular disease (CVD), cancer, and respiratory mortality. Associations with all-cause and cause-specific mortality were examined using multivariable Cox proportional hazards and competing-risks regression. RESULTS: There were 1,652 men with RA and 332 deaths. The leading causes of death were CVD (31.6%; SMR 1.77 [95% confidence interval (95% CI) 1.46-2.14]), cancer (22.9%; SMR 1.50 [95% CI 1.20-1.89]), and respiratory disease (15.1%; SMR 2.90 [95% CI 2.20-3.83]). Factors associated with all-cause mortality included older age, white race, smoking, low body weight, comorbidity, disease activity, and prednisone use. Rheumatoid factor concentration and nodules were associated with CVD mortality. There were no associations of methotrexate or biologic agent use with all-cause or cause-specific mortality. CONCLUSION: Men in this RA cohort experienced increased all-cause and cause-specific mortality, with a 3-fold risk of respiratory-related deaths compared to age-matched men in the general population. Further studies are needed in order to examine whether interventions targeting potentially modifiable correlates of mortality might lead to improved long-term survival in men with RA. | |
27861525 | Elevated Neopterin Levels Are Associated with Increased Tuberculosis Risk in Rheumatoid Ar | 2016 | QuantiFERON-TB-Gold (QFT-G) conversion is frequently observed in rheumatoid arthritis (RA) patients receiving biologic therapy. However, there have not been any known biomarkers available for detecting tuberculosis (TB) in QFT-G converters. We aimed to evaluate clinical utility of cytokines/chemokines for detecting TB in patients with QFT-G conversion. Among a total of 227 RA patients who underwent QFT-G assay, 187 QFT-G-negative patients received biologic therapy without isoniazid prophylaxis. QFT-G assay was repeated at week 52 of biologic therapy or at the time of TB diagnosis. Levels of cytokines/chemokines were determined by magnetic bead array or ELISA in QFT-G converters and 12 non-RA patients with TB (non-RA TB). QFT-G conversion was found in 54 (28.9%) of 187 baseline QFT-G-negative patients, of which 7 (13.0%) developed active TB during the one-year follow-up period. Among the examined cytokines/chemokines, non-stimulated and TB-antigen-stimulated neopterin levels were significantly higher in RA patients who developed TB (RA-TB) (median, 24.5pg/ml and 23053pg/ml, respectively) and non-RA TB patients (12.2pg/ml and 9633pg/ml, respectively) compared with QFT-G converters without TB (3.0pg/ml and 2720pg/ml, respectively, both p<0.001). Rising levels of neopterin relative to baseline (non-stimulated levels, 4.4pg/ml vs. 24.5pg/ml; TB-antigen-stimulated levels, 1801pg/ml vs. 23053pg/ml) were observed in QFT-G converters who developed TB. A high proportion (85.7%) of QFT-G converters with high plasma neopterin levels developed TB during the one-year follow-up period. In conclusion, RA patients with QFT-G conversion during the period of biologic therapy should be carefully monitored for elevation of neopterin levels, which is associated with TB risk in QFT-G converters, particularly in TB-endemic areas. | |
27238964 | Effectiveness of treatment with biologic- and disease-modifying antirheumatic drugs in rhe | 2016 Jun | AIMS: Rheumatoid arthritis (RA) is an autoimmune disease cause of disability and high costs. To determine the effectiveness of therapy with biologic- and disease-modifying antirheumatic drugs (DMARDs) in patients with RA and factors associated with the control of the disease. METHODS: Retrospective cohort study of RA patients receiving treatment with DMARDs in a rheumatologic healthcare institution in five Colombian cities from December 2009 to August 2013. The effectiveness was assessed by Disease Activity Score-28 (DAS-28) and a lower value of 2.6 was considered remission. RESULTS: A total of 827 patients were studied for an average observation period of 17.3 ± 11.0 months, with mean age 54.3 ± 13.1 years. The most frequently used DMARDs were methotrexate, leflunomide and chloroquine. The most frequently used biological DMARDs were etanercept and abatacept. Initially, 17.8% of the patients received some biological DMARDs in comparison with 28.7% at the end of the observation period. A median DAS28 of 3.5 was found, which was reduced by the end of the observation period to 2.8 (p < 0.001), and cases of patients who were in remission increased from 30.1% to 42.9%. Treatment with leflunomide (OR: 0.47; CI 95%: 0.35-0.64, p < 0.001) or rituximab (OR: 0.37; CI 95%: 0.17-0.83, p = 0.016) was associated with a lesser probability of reaching remission. To be treated in the city of Manizales (OR: 2.56; CI 95%: 1.36-4.82, p = 0.004) was associated with a high probability of remission. CONCLUSIONS: Biological and DMARDs therapy for RA was effective in a relevant proportion of Colombian patients as a consequence of management with strategies set on remission aims quantified using DAS28. Cost-effectiveness of the therapy must be evaluated. | |
27753285 | HLA class II alleles influence rheumatoid arthritis susceptibility and autoantibody status | 2016 Nov | Rheumatoid arthritis (RA) is a complex multifactorial autoimmune disease characterized by inflammatory arthritis. The precise etiology and pathogenesis of RA remains elusive but evidence points towards stochastic interactions between genetic and environmental factors. This study investigated the distribution of human leucocyte antigen (HLA)-DRB1/DQB1 alleles in South Indian patients with rheumatoid arthritis (RA) and their influence on RA susceptibility and clinical phenotype. Low resolution HLA-DRB1 and -DQB1 typing was performed in 271 RA patients and 233 healthy controls by polymerase chain reaction (PCR) using sequence-specific primers (SSP). HLA-DRB1*10 was found to be more frequent in patients (P(c) = 0.004, OR = 2.23, 95% CI = 1.5-3.34) than controls. This difference persisted in RF positive (P(c) = 9 × 10(-6) , OR = 2.45, 95% CI = 1.62-3.74), ACPA positive (P(c) = 0.007, OR = 2.10, 95% CI = 1.35-3.29), ACPA negative (P(c) = 0.001, OR = 2.45, 95% CI = 1.50-3.97) and both RF and ACPA positive subgroup of patients (P(c) = 0.003, OR = 2.22, 95% CI = 1.41-3.51). On the contrary, the HLA-DRB1*13 (P(c) = 0.01, OR = 0.43, 95% CI = 0.25-0.73) and HLA-DRB1*14 (P(c) = 0.003, OR = 0.43, 95% CI = 0.26-0.69) alleles were over-represented in controls than patients. Further, distribution of the prominent Caucasian RA risk allele DRB1*04 did not differ between patients and controls in our study population. We did not find any association between DQB1 alleles and RA susceptibility or autoantibody status. The haplotypes DQB1*05-DRB1*10 (P = 6.8 × 10(-6) , OR = 2.46, 95% CI = 1.63-3.79) and DQB1*06-DRB1*15 (P = 0.03, OR = 1.41, 95% CI = 1.02-1.96) were more frequent in patients while DQB1*05-DRB1*14 (P = 8.4 × 10(-4) , OR = 0.44, 95% CI = 0.26-0.74) and DQB1*06-DRB1*13 (P = 9.5 × 10(-4) , OR = 0.40, 95% CI = 0.21-0.72) were higher in controls. To conclude, HLA-DRB1*10 is associated with RA while HLA-DRB1*13 and HLA-DRB1*14 alleles confer protection in south Indian Tamils. | |
26099279 | Risk of malignancy in patients with rheumatoid arthritis, psoriatic arthritis and ankylosi | 2016 Feb | Systemic inflammatory rheumatic diseases are associated with an increased risk of malignancy, in particular of lymphoproliferative disorders. Chronic inflammation, due to the disease itself, generates a microenvironment able to promote cancer development, but it is still controversial whether immunosuppressive therapy may contribute to carcinogenesis. The aim of the study was to evaluate the risk of malignancy in 399 patients affected by rheumatoid arthritis (RA), psoriatic arthritis and ankylosing spondylitis, all treated with either tumor necrosis factor α-inhibitors plus disease-modifying anti-rheumatic drugs (DMARDs) or DMARDs alone. The risk of malignancy in this cohort of patients, observed in the period between 2005 and 2011 at S. Andrea Hospital-Sapienza University of Rome, was compared with that of the general Italian population, matched for age, sex, and area of residence. Fourteen (3.5%) malignancies, five of which were hematologic, have been observed. The overall cancer risk was not significantly increased in comparison to the general population, whereas the risk of hematologic malignancies appeared significantly higher in RA patients (SIR 4.94, 95% CI 1.35-12.64), particularly in female gender (SIR 6.9, 0.95% CI 1.88-17.66). No significant association between therapy and malignancy was demonstrated in RA patients. | |
25259409 | Cellular energy metabolism in T-lymphocytes. | 2015 Jan | Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders. | |
27783235 | Welfare costs in patients with rheumatoid arthritis and their partners compared with match | 2017 Mar | Rheumatoid arthritis (RA) is a chronic autoimmune disease with significant morbidity, mortality, and costs for the individual patient and for society. The purpose of this study was to examine welfare costs in patients with RA including their partners before and after initial diagnosis. Data were collected from population-based registers in the period from 1998 to 2009. A total of 25,547 Danish patients with a diagnosis of RA and 15,660 of their partners were identified and compared with 101,755 randomly selected age- and gender-matched controls and 62,681 control partners. The direct and indirect costs were calculated for patients and their partners and compared to matched controls. These included inpatient and outpatient treatment, medication, income from employment and social transfer payments. Patients with RA had statistically significantly more inpatient and outpatient costs than control subjects, i.e., treatment (€346 vs. €211), hospitalization (€1261 vs. €778), and medication use (€654 vs. €393). The costs associated with the patients were present 11 years before diagnosis of RA (€1592) compared with control subjects (€1172). Furthermore, income from employment was lower for patients (€14,023) than for control subjects (€17,196). Being a partner to a patient with RA was associated with high total welfare costs. This register-based study shows that RA has significant welfare costs for patients, their partners, and society. The differences in total health costs exist up to 11 years before the diagnosis of RA is established. | |
27749595 | Perceived and actual risk of cardiovascular disease in patients with rheumatoid arthritis | 2016 Oct | The purposes of this study were to compare the perceived and actual 10-year risk for cardiovascular disease (CVD) and to evaluate the influence of cardiovascular risk factors on perceived CVD risk in patients with rheumatoid arthritis (RA) in Korea. Additionally, the attainment of CVD prevention guideline goals by 3 levels of CVD risk (low, moderate, and high) was presented.For this cross-sectional study, data were collected from 208 patients with RA. Actual CVD risk was estimated with the Systematic Coronary Risk Evaluation (SCORE), and goal attainment was assessed based on the European League Against Rheumatism guidelines. Actual CVD risk and perceived risk were compared with cross-tabulation. Chi-square tests were used to evaluate differences in cardiovascular risk factors by perceived risk. Levels of goal attainment were presented in percentages.Among patients with RA, 13.9% were identified as being at high risk for CVD, whereas 39.9% were at moderate risk, and 46.2% were at low risk. The majority of those at high risk (96.6%) underestimated their risk for CVD. The use of antihypertensive or lipid-lowering medications and having a parental history of CVD significantly increased the likelihood that subjects with RA would perceive themselves as being at high risk for CVD. Diabetes, smoking, physical inactivity, and obesity did not affect perceived risk. A substantial proportion of the subjects with RA did not meet the prevention guideline goals.Patients with RA who are at increased risk of developing CVD must be managed as soon as possible to attain the guideline goals and, accordingly, lower their risk of future CVD. | |
26315693 | A comparison of rheumatoid arthritis and systemic lupus erythematosus trial design: a comm | 2015 Sep | OBJECTIVES: Recent systemic lupus erythematosus (SLE) randomised controlled trials (RCTs) were examined for potential design flaws and compared to rheumatoid arthritis (RA) RCT over the same time period to suggest modifications to SLE RCTs that could help improve the potential success rate of future SLE trials. METHODS: RA and SLE biologics RCTs published between 2005 and July 2013 were identified using PubMed. Inclusion criteria, study design, outcome measures, sample size calculations, patient baseline characteristics steroid use in the protocol and results were extracted and compared. RESULTS: All trials required active disease for enrolment. Twenty-two RA RCTs and eight SLE RCTs were included. All RA RCTs used either a partial or continuous measure of improvement. SLE RCTs used SLEDAI, BILAG, SLAM, SRI and BICLA. RA trials were larger (543 vs. 376 participants). Concomitant corticosteroid use was stable in 100% of RA trials while all SLE RCTs allowed dose tapering. RA trials were mostly in methotrexate or DMARD inadequate responders whereas SLE trials allowed for the presence or absence immunosuppressives within all trials. Sample sizes in RA were determined on a change in disease activity or proportion meeting a disease state. Positive trials were found in 100% of RA RCTs and 25% of SLE RCTs. CONCLUSIONS: The potential insensitivity of SLE disease activity indices to partial improvements may result in type II errors in SLE RCTs. Varying concomitant pharmacotherapy, especially corticosteroid use, in SLE may blunt observed treatment effects. Steroid tapering should be considered a trial outcome in isolation. More realistic sample size calculations are needed in SLE. |