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ID PMID Title PublicationDate abstract
23144446 Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheum 2013 Apr BACKGROUND: Suppression of the immunoinflammatory cascade by targeting interleukin 6 (IL-6) mediated effects constitutes a therapeutic option for chronic inflammatory diseases. Tocilizumab is the only IL-6 inhibitor (IL-6i) licensed for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), but also other agents targeting either IL-6 or its receptor are investigated in various indications. OBJECTIVE: To review published evidence on safety and efficacy of IL-6i in inflammatory diseases. METHODS: We performed systematic literature searches in Medline and Cochrane, screened EULAR and American College of Rheumatology meeting-abstracts, and accessed http://www.clinicaltrials.gov. RESULTS: Comprehensive evidence supports the efficacy of tocilizumab in RA in DMARD-naïve patients, and after DMARD- and TNFi-failure. Randomised comparisons demonstrate superiority of tocilizumab in JIA, but not ankylosing spondylitis (AS). Other indications are currently investigated. Additional IL-6i show similar efficacy; safety generally appears acceptable. CONCLUSIONS: IL-6i is effective and safe in RA and JIA, but not in AS. Preliminary results in other indications need substantiation.
22249200 Novel regulatory mechanisms in inflammatory arthritis: a role for microRNA. 2012 Mar Elucidating pathways that regulate cytokine production in the context of autoimmune disease will likely lead to the development of novel therapeutics. Herein, we review data suggesting that microRNAs (miRs) represent one such level of regulatory activity, with particular emphasis on the pathogenesis of rheumatoid arthritis (RA). A series of miRs have been identified to be dysregulated in cell subsets within the articular compartment of patients with RA. These have a critical role in regulating cartilage-invading phenotype of RA synovial fibroblasts. More recently, several studies suggest that miRs also regulate leukocyte activation and cytokine production that in turn contribute to the immunologic component of effector synovial pathology. Together, these observations open an exciting new vista of understanding and therapeutic opportunity for this difficult and common disease.
21452293 Atacicept in patients with rheumatoid arthritis and an inadequate response to tumor necros 2011 Jul OBJECTIVE: To assess the efficacy, safety, and biologic activity of atacicept in patients with rheumatoid arthritis (RA) in whom the response to treatment with tumor necrosis factor antagonists was inadequate. METHODS: The Atacicept for Reduction of Signs and Symptoms in Rheumatoid Arthritis Trial (AUGUST I) was a multicenter, phase II, double-blind, placebo-controlled dose-finding study involving 256 patients randomized 1:1:1:1 to receive atacicept (25 mg, 75 mg, or 150 mg) or placebo twice weekly for 4 weeks, then weekly for 21 weeks, with a 13-week treatment-free followup period (week 38). The primary end point was a response at week 26 according to the American College of Rheumatology criteria for 20% improvement in disease severity, using the C-reactive protein level. RESULTS: No statistically significant differences were observed in the efficacy end points at week 26 (P = 0.410 for overall treatment effect). However, atacicept significantly reduced immunoglobulin and rheumatoid factor (RF) levels, but not anti-citrullinated protein antibody levels, in a dose-dependent manner, with levels returning toward baseline values during followup. The effects of treatment on IgG-RF and IgA-RF were more pronounced than the effects on total IgG and IgA. Adverse events (AEs), including serious AEs, leading to withdrawal were more common among patients treated with atacicept compared with placebo. AEs were variable in nature, and no dose-dependent trends were observed. The frequency of infection-related AEs was similar across treatments. No notable effect of treatment on immunization status (protective versus nonprotective titer) was observed after initiation of treatment. CONCLUSION: This study did not meet the primary efficacy end point. However, clear biologic activity consistent with the proposed mechanism of action was observed. The results suggest that decreasing the expression of RF may not be sufficient to induce clinical improvement in RA. The safety of atacicept was considered acceptable in this patient population.
21531491 Understanding the effect of disease adaptation information on general population values fo 2011 Jun It has been recommended that economic evaluation of healthcare technologies should use values for hypothetical health states elicited from the general population rather than patients. The drawback is the general population may not consider the possibility of adapting to the impaired state. This study explored the extent to which the general population changes their initial values, and the factors that influenced this change, after being informed with different disease adaptation techniques. Three rheumatoid arthritis states were used for illustration. General population respondents from the United Kingdom initially valued the states. An adaptation exercise followed, where they listened to recordings of patients discussing how they adapted; they then valued the same states again. The differences between the valuations were examined using t-tests. A multivariate regression model was developed to assess the factors that impacted individuals to change their initial values. After undergoing the adaptation exercise, the respondents increased their values for the rheumatoid arthritis states. Younger and healthier individuals were more likely to increase their initial values after being informed.
22187054 Stevens-Johnson syndrome complicating adalimumab therapy in rheumatoid arthritis disease. 2013 May The efficacy of adalimumab, a fully human anti-tumor necrosis factor-α recombinant antibody, has dramatically improved the quality of life of patients with rheumatoid and psoriatic arthritis and Crohn's disease. Because it is fully human, one should not expect immune reactions to this molecule. Adverse reactions to adalimumab are limited mainly to injection site reactions and are very common. We, however, report a case of Stevens-Johnson syndrome that required hospitalization and cessation of adalimumab in a patient with rheumatoid arthritis (RA). In this case report, a 53-year-old woman with RA developed severe mucositis, peripheral rash and desquamation and fever concomitant with the fifth dose of 40 mg adalimumab. Infective etiologies were excluded. The patient responded rapidly to IV hydrocortisone and was able to be commenced on infliximab without recurrence of the Stevens-Johnson syndrome. Severe skin reactions induced by TNF-α antagonists can be very serious, and prescribers need to be aware of the potential for the mucocutaneous adverse effects from the use of these agents, particularly due to the significant morbidity and mortality that are associated with SJS.
21153677 Non-invasive screening of progressive joint defects in the Type II collagen-induced arthri 2011 May OBJECTIVE: This study presents a method for non-invasive screening of progressive arthritic reactions in a representative rheumatoid arthritis (RA) animal model of Type II collagen-induced arthritis (CIA). MATERIALS: Seventeen male DBA/1J mice (9 weeks old) were used for the control group (seven) and the CIA group (ten). TREATMENT: The CIA model was induced by the injection of a Type II collagen and incomplete Freund's adjuvant emulsion. METHODS: Arthritic reactions including joint space narrowing (JSN), bone erosion, inflammation, and physiological defects were observed using five non-invasive methods. The degrees of JSN and bone erosion were quantified using macro-radiographs of specific joints and bones, while the severity of inflammation was evaluated by changes in paw volume and visual scoring of edema and erythema. RESULTS: Significant differences were observed in JSN (≤48.29%, p < 0.0001), bone erosion (78.30%, p < 0.0001), grip strength (p < 0.05), and inflammation (91.67% in edema and 194.12% increase in paw volume, p < 0.001) between the CIA group and the controls. The relationships between factors exhibited significant positive correlations (R ≥ 0.9229, p < 0.05) between radiographic parameters, with symmetries of ≥0.9062 (p < 0.05) for JSN and ≥ 0.8575 (p < 0.001) for bone erosion, 0.8770 (p < 0.0001) for inflammatory parameters, and ≥0.9527 (p < 0.0001) for radiographic and non-radiographic parameters. CONCLUSIONS: Our non-invasive radiographic and non-radiographic methods of documentation were both acceptable for screening joint defects during RA progression. In addition, the results of this study may be useful for monitoring the progression of joint pathology in RA diseases.
21567382 Baseline serum adipokine levels predict radiographic progression in early rheumatoid arthr 2011 Sep OBJECTIVE: Adipose tissue can secrete soluble mediators (adipokines) with potent immune regulatory functions. Some adipokines have been previously associated with radiographic damage in patients with rheumatoid arthritis (RA). In the present study, we investigated the capacity of baseline adipokine levels to predict radiographic progression over a period of 4 years and studied their contribution relative to that of other known risk factors, such as anti-cyclic citrullinated peptide (anti-CCP) antibodies. METHODS: Serum concentrations of leptin, visfatin, resistin, adiponectin, adipsin, tumor necrosis factor α (TNFα), and interleukin-6 (IL-6) were determined in serum samples obtained at baseline from 253 patients with RA from the Early Arthritis Cohort. The association between levels of these adipokines and radiographic progression was determined using a multivariate normal regression model correcting for age, sex, treatment strategy, body mass index (BMI), and the presence of anti-CCP antibodies. RESULTS: Levels of IL-6, TNFα, visfatin, and adiponectin were positively associated with radiographic progression over 4 years. This association was independent of BMI. However, only adiponectin levels remained significantly associated with radiographic progression when the model was corrected for the presence of anti-CCP antibodies, whereas a trend was observed for IL-6. The association of both TNFα and visfatin with radiographic damage disappeared after correction for the presence of anti-CCP antibodies, which is consistent with the fact that the levels of both cytokines correlated significantly with anti-CCP antibody levels in these patients. CONCLUSION: Our results indicate that adipokines are predictors of radiographic progression in RA, possibly through distinct underlying biologic mechanisms.
22055542 Hand tendon involvement in rheumatoid arthritis: an ultrasound study. 2012 Jun OBJECTIVE: To assess the prevalence and the distribution of tendon involvement in the hands and wrists of patients with rheumatoid arthritis (RA) describing in detail the ultrasound (US) morphostructural and vascular tendon abnormalities. METHODS: Ninety consecutive RA patients were included in the study. The following tendons were scanned bilaterally: flexor pollicis longus tendon, flexor digitorum superficialis, and profundus tendons of the II to the V fingers (at both finger and carpal tunnel levels), flexor carpi radialis tendon, and extensor tendons of the 6 compartments on the dorsal aspect of the wrist. The presence of US findings indicative of tenosynovitis and tendon damage was investigated. RESULTS: Tenosynovitis was found in at least 1 anatomic site of 44 (48.8%) of 90 patients. Tendon damage was found in at least 1 anatomic site of 39 (43.3%) of 90 patients. The focal tendon echotexture derangement was found in 294 of 5400 (5.4%) tendons, the partial and complete tears in 14 (0.3%), and in 3 (0.06%) tendons, respectively. The most frequently involved tendons were the flexor tendons of the II, III, and IV fingers and the extensor carpi ulnaris tendon. CONCLUSIONS: The present study provides evidence in favor of the ability of US to reveal a relatively high frequency of tendon involvement at the hand and wrist level in RA patients. These data can both facilitate US examinations in daily clinical practice and direct further investigations in the US assessment of tendon involvement in RA.
21262393 Switching rheumatoid arthritis treatments: an update. 2011 May The first approved biological agents for the treatment of rheumatoid arthritis (RA) were tumour necrosis factor (TNF) antagonists, all of which improve disease signs and symptoms, and slow or prevent structural damage; however, they are not equally effective in all patients. About 30% of patients treated with a TNF agent fail to achieve an improvement of 20% in the American College of Rheumatology (ACR) criteria, and even more patients lose efficacy during therapy or experience adverse events. Switching to a second TNF inhibitor has become an established approach to patients who fail or are intolerant of treatment with the first. However, there is only one published large randomised clinical trial evaluating the benefits of switching TNF antagonists, and data from observational studies and clinical practice are conflicting. Many parameters influence switching TNF agents, including the type of failure or TNF antagonist. However, many RA patients can be successfully treated with a second TNF antagonist, especially those discontinuing the first because of secondary failure or adverse events.
21041278 Effect of atorvastatin on inflammation and modification of vascular risk factors in rheuma 2011 Feb OBJECTIVE: To investigate the effect of atorvastatin therapy on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: This study included 30 patients with early RA, randomly divided into 2 groups. Group 1 (n = 15) received methotrexate (MTX; 0.2 mg/kg/week; mean (15.5 ± SD 1.3) plus prednisone (10 mg/day). Group 2 (n = 15) received MTX and prednisone with the same previous doses plus atorvastatin therapy (40 mg/day). Ten healthy individuals of similar age and sex served as controls. Disease activity, lipid profile, serum malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), resistin, adiponectin, and brachial artery flow-mediated dilation (FMD) were measured before and after 6 months of treatment. RESULTS: Atorvastatin combined with MTX therapy significantly reduced serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and increased high-density lipoprotein cholesterol (p < 0.001). Disease activity variables, serum MDA, TNF-α, resistin, adiponectin, and FMD were significantly improved by the drug combinations (p < 0.001). CONCLUSION: Atorvastatin therapy in patients with RA reduced disease activity and conventional and novel vascular risk factors that promote the atheromatous lesion. Therapy was also associated with concomitant improvement in endothelial function.
21923476 Synovial and serum levels of uncarboxylated matrix Gla-protein (ucMGP) in patients with ar 2011 Sep 17 BACKGROUND: Matrix Gla-protein (MGP) is a calcification inhibitor produced by cartilage and vessel walls. Arthritis is defined by inflammation, cartilage and bone destruction/formation and articular calcifications. Our objectives were to evaluate ucMGP levels in synovial fluid (SF) in arthritis patients and to investigate the relationship between local and circulating ucMGP and their association with age and inflammation. METHODS: Arthritis patients (n=26) with knee joint effusion and controls (n=30) underwent an ultrasonographic knee examination for articular calcifications assessment. Patients were divided into inflammatory and non-inflammatory groups. ucMGP levels were determined in serum and SF using a competitive ELISA assay. RESULTS: Within the arthritis patients, the inflammatory group had the lowest ucMGP serum levels, and the highest levels of synovial ucMGP. Furthermore, the inflammatory group had significantly (p<0.05) higher RucMGP (synovial ucMGP/serum ucMGP*100) than the non-inflammatory group [36 (17-69) vs. 24 (5-55)], and this parameter positively correlated (r=0.4; p<0.05) with the erythrocyte sedimentation rate (ESR). No correlation was found between age and local or circulating ucMGP in patients and controls. CONCLUSIONS: The ucMGP assay can be used for determination of MGP in SF, and combined assessment of ucMGP in serum and SF could potentially serve as a joint inflammatory marker in arthritis patients.
22073937 Potential advantages of interprofessional care in rheumatoid arthritis. 2011 Nov BACKGROUND: Rheumatoid arthritis (RA) affects over 1 million people in the United States. Although the emergence of new medications has substantially improved treatment options and outcomes for patients with RA, the disease is still a major cause of morbidity and mortality. In addition, significant barriers to adherence characterize RA medication management. A reasonable approach to improving RA patient outcomes entails interprofessional, multidisciplinary models of care. Working with rheumatology specialists, RA multidisciplinary care teams may comprise case managers, pharmacists, physical and occupational therapists, social workers, physiatrists, orthopedists, or other health professionals. Experience and evidence have supported the value of interprofessional, coordinated care models for patients with various chronic diseases. However, potential drawbacks include the costs associated with implementation of such approaches, the extra time required for their administration, and the lack of incentives for clinicians to adopt collaborative care approaches. OBJECTIVES: To summarize the arguments and evidence for interprofessional, multidisciplinary care programs in RA. SUMMARY: Various multidisciplinary models of RA care have been described in the literature. Whereas the case for implementing such models is underscored by the chronic nature of the disease, by its comorbidities and complications, and by barriers to patient medication adherence, cost-effectiveness analyses to document benefits of coordinated interprofessional RA care are lacking. Most studies on interprofessional care in RA are relatively old and have been conducted outside of the United States. Nonetheless, the findings are still relevant and may shed light on potential avenues for the development of new models in this country.
21405936 Clinical periodontal and microbiologic parameters in patients with rheumatoid arthritis. 2011 Oct BACKGROUND: A limited number of studies suggest a prevalence of periodontal pathogens in patients with rheumatoid arthritis (RA); however, results are inconsistent. The aim of this study is to investigate clinical periodontal and microbiologic parameters in patients with RA. METHODS: Sixty-six patients with RA, aged 49.5 ± 8.4 years, participated in the study. The periodontal classification was assessed with the periodontal screening index (PSR/PSI) allocated to the following parameters: 1) healthy; 2) gingivitis (PSR/PSI score 0 to 2, maximum one sextant score; 3) moderate periodontitis (>1 sextant PSR/PSI score 3, maximum one sextant score; or, 4) severe periodontitis (>1 sextant PSR/PSI score 4). Pool samples were taken for microbiologic (polymerase chain reaction) analysis for the presence of 11 periodontal pathogens. Statistical analysis was by non-parametric analysis of covariance. RESULTS: No patients were periodontally healthy: 24 patients were classified as having gingivitis; 18 patients had moderate periodontitis; 23 patients had severe periodontitis; and one patient was toothless. For most patients, Fusobacterium nucleatum (98%), Eikenella corrodens (91%), and Parvimonas micra (previously Peptostreptococcus micros; 88%) were above the detection threshold. Strong periodontal pathogens were less frequently detected: Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans, 16%); Porphyromonas gingivalis (58%); and Tannerella forsythia (previously T. forsythensis, 78%). Statistical analysis showed no significant influence of rheumatic factor (P = 0.33) on periodontal classification and on microbiologic parameters (P >0.05). Only smoking showed a significant influence (P = 0.0004) on the periodontal classification and in the case of E. corrodens (P = 0.02). CONCLUSIONS: Most patients with RA in this study showed moderate-to-severe periodontitis and the presence of periodontal pathogens. No association was found between rheumatic factor on periodontal classification and microbiologic parameters.
22568189 [Medical and legal aspects of smoking]. 2012 Mar Tobacco is known worldwide for several thousand years. Smoking is the strongest and most common type of addiction. The harmful effect of tobacco on the human body leads to the development of cancer, respiratory, cardiovascular, skin diseases. It was also noted adverse effects of tobacco on inflammatory and immunologic phenomena. Taken numerous legal actions aimed at reducing the negative health effects among smokers as well as measures to reduce exposure to tobacco smoke of people from the surroundings.
21425888 Strength training as a countermeasure to aging muscle and chronic disease. 2011 Apr 1 Strength training (ST) has long been considered a promising intervention for reversing the loss of muscle function and the deterioration of muscle structure associated with advanced age but, until recently, the evidence was insufficient to support its role in the prevention or treatment of disease. In recent decades, there has been a long list of quality reviews examining the effects of ST on functional abilities and a few on risk factors for specific diseases, but none have provided a comprehensive assessment of ST as an intervention for a broad range of diseases. This review provides an overview of research addressing the effectiveness of ST as an intervention for the prevention or treatment of the adverse consequences of (i) aging muscle; (ii) the metabolic syndrome (MetS) and its components, i.e. insulin resistance, abdominal obesity, hyperlipidaemia and hypertension; (iii) fibromyalgia; (iv) rheumatoid arthritis; and (v) Alzheimer's disease. Collectively, these studies indicate that ST may serve as an effective countermeasure to some of the adverse consequences of the MetS, fibromyalgia and rheumatoid arthritis. Evidence in support of the hypothesis that ST reduces insulin resistance or improves insulin action comes both from indirect biomarkers, such as glycosylated haemoglobin (HbA(1c)), and insulin responses to oral glucose tolerance tests, as well as from more direct procedures such as hyperglycaemic and hyperinsulinaemic-euglycaemic clamp techniques. The evidence for the use of ST as a countermeasure of abdominal obesity is less convincing. Although some reports show statistically significant reductions in visceral fat, it is unclear if the magnitude of these changes are physiologically meaningful and if they are independent of dietary influences. The efficacy of ST as an intervention for reducing dyslipidaemia is at best inconsistent, particularly when compared with other pharmacological and non-pharmacological interventions, such as aerobic exercise training. However, there is more consistent evidence for the effectiveness of ST in reducing triglyceride levels. This finding could have clinical significance, given that elevated triglyceride is one of the five criterion measures for the diagnosis of the MetS. Small to moderate reductions in resting and exercise blood pressure have been reported with some indication that this effect may be genotype dependent. ST improves or reverses some of the adverse effects of fibromyalgia and rheumatoid arthritis, particularly pain, inflammation, muscle weakness and fatigue. Investigations are needed to determine how these effects compare with those elicited from aerobic exercise training and/or standard treatments. There is no evidence that ST can reverse any of the major biological or behavioural outcomes of Alzheimer's disease, but there is evidence that the prevalence of this disease is inversely associated with muscle mass and strength. Some indicators of cognitive function may also improve with ST. Thus, ST is an effective countermeasure for some of the adverse effects experienced by patients of many chronic diseases, as discussed in this review.
21801431 Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis pat 2011 Jul 30 INTRODUCTION: The objective of this study was to investigate the effects of tumor necrosis factor (TNF)-α inhibitors on circulating T helper-type 17 (Th17) cells and Th17-related cytokines in patients with rheumatoid arthritis (RA). METHODS: The frequencies of circulating Th17 cells and serum levels of Th17-related cytokines were determined using flow cytometry analysis and ELISA, respectively, in 48 RA patients both before (baseline) and six months after anti-TNF-α therapy. Therapeutic response was evaluated using European League Against Rheumatism (EULAR) response criteria. RESULTS: Significantly higher baseline frequencies of circulating Th17 cells and serum levels of interleukin (IL)-6, IL-17, IL-21, IL-23 and TNF-α were observed in active RA patients than in 12 healthy controls (all P < 0.001). After anti-TNF-α therapy, 36 patients (75%) were EULAR responders (20 good responders and 16 moderate responders) and 12 (25.0%) were non-responders. The mean levels of circulating Th17 cells and IL-17 significantly decreased (1.13% vs. 0.79%; 43.1 pg/ml vs. 27.8 pg/ml; respectively, both P < 0.001) in parallel with clinical remission in responders. Levels of IL-6, IL-21, IL-23 and TNF-α were significantly decreased after anti-TNF-α therapy in responders. In contrast, the mean levels of circulating Th17 cells and IL-17 significantly increased after anti-TNF-α therapy (2.94% vs. 4.23%; 92.1 pg/ml vs. 148.6 pg/ml; respectively, both P < 0.05) in non-responders. Logistic regression analysis identified a high baseline level of IL-17 as a significant predictor of poor therapeutic response. CONCLUSIONS: The beneficial effect of anti-TNF-α therapy might involve a decrease in Th17-related cytokines in responders, whereas rising levels of circulating Th17-cells and IL-17 were observed in patients with an inadequate response to anti-TNF-α therapy.
21791135 [Determining cardiovascular risk in patients with rheumatoid arthritis: waiting for trial 2011 Cardiovascular risk management is clearly indicated in patients with rheumatoid arthritis (RA) today because this risk is comparable to patients with diabetes. Although formal evidence of cardiovascular endpoint trials with statins and/or antihypertensives is lacking in patients with RA, there are no indications that these drugs will have limited effect. In contrast, there is accumulating evidence as to the efficacy of the use of these drugs in RA that is at least comparable to their effects in the general population. All patients with RA should therefore receive cardiovascular risk-management therapy aimed at powerful suppression of the chronic inflammatory process as well as treatment with statins and/or antihypertensives, if indicated. Obviously, monitoring in the clinical setting is necessary to document if such therapy does indeed reduce cardiovascular disease in patients with RA.
21807798 The PROMIS of better outcome assessment: responsiveness, floor and ceiling effects, and In 2011 Aug OBJECTIVE: Use of item response theory (IRT) and, subsequently, computerized adaptive testing (CAT), under the umbrella of the NIH-PROMIS initiative (National Institutes of Health-Patient-Reported Outcomes Measurement Information System), to bring strong new assets to the development of more sensitive, more widely applicable, and more efficiently administered patient-reported outcome (PRO) instruments. We present data on current progress in 3 crucial areas: floor and ceiling effects, responsiveness to change, and interactive computer-based administration over the Internet. METHODS: We examined nearly 1000 patients with rheumatoid arthritis and related diseases in a series of studies including a one-year longitudinal examination of detection of change; compared responsiveness of the Legacy SF-36 and HAQ-DI instruments with IRT-based instruments; performed a randomized head-to-head trial of 4 modes of item administration; and simulated the effect of lack of floor and ceiling items upon statistical power and sample sizes. RESULTS: IRT-based PROMIS instruments are more sensitive to change, resulting in the potential to reduce sample size requirements substantially by up to a factor of 4. The modes of administration tested did not differ from each other in any instance by more than one-tenth of a standard deviation. Floor and ceiling effects greatly reduce the number of available subjects, particularly at the ceiling. CONCLUSION: Failure to adequately address floor and ceiling effects, which determine the range of an instrument, can result in suboptimal assessment of many patients. Improved items, improved instruments, and computer-based administration improve PRO assessment and represent a fundamental advance in clinical outcomes research.
21904923 Tolerogenic dendritic cells and rheumatoid arthritis: current status and perspectives. 2012 Apr Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the influxation of synovia and synovial compartments with immune cells including dendritic cells (DCs). DCs that induce autoimmune tolerance are called tolerogenic DCs (tolDCs). As a promising immunotherapeutic strategy for RA, tolDCs have received increasing attention. In this review, we first introduce the significant role of tolDCs in autoimmune regulation and then describe the manipulation strategies to generate tolDCs; next, we summarize recent progress in the experimental application of tolDCs for RA therapy, and finally we discuss the perspectives of tolerogenic vaccination for the treatment for RA in clinic.
22744978 Dietary intake of vitamin D during adolescence and risk of adult-onset systemic lupus eryt 2012 Dec OBJECTIVE: Vitamin D has immunomodulatory properties with potential etiologic implications for autoimmune diseases. The relevant exposure time during which vitamin D may influence disease risk is unknown. Our objective was to examine the relationship between reported vitamin D intake during adolescence and adult-onset rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) incidence in prospective cohort studies of women, the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII). METHODS: Food frequency questionnaires concerning high school diet completed by 73,629 NHS (1986) and 45,544 NHSII (1998) participants were used to calculate nutrient intakes during adolescence. Incident RA and SLE cases prior to 2006 (NHS) and 2007 (NHSII) were confirmed by medical record review. Cox proportional hazards models calculated relative risks and 95% confidence intervals of incident RA and SLE according to quintile cutoffs of vitamin D intake. Age- and calorie-adjusted and multivariable-adjusted (including sun exposure factors) analyses were completed. Random-effects models were used to meta-analyze estimates of association from the 2 cohorts. RESULTS: Incident RA was confirmed in 652 NHS and 148 NHSII participants and SLE was confirmed in 122 NHS and 54 NHSII participants over a mean followup time of 351 months (NHS) and 209 months (NHSII). Age- and calorie-adjusted and multivariable-adjusted models did not show significant associations between adolescent vitamin D intake and risk of adult-onset RA or SLE. CONCLUSION: We did not find associations between adolescent dietary vitamin D intake and adult RA or SLE risk among NHS and NHSII women, suggesting that other time periods during the life course should be studied.