147 research outputs found
Disease activity states, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept
The advent of biologic medications has increased considerably the potential for treatment benefit in juvenile idiopathic arthritis (JIA), with clinical remission being now achievable in a substantial proportion of patients. However, there is a need of data from the real world of clinical practice to evaluate thoroughly the efficacy and safety profile of the biologic agents currently approved
Efficacy and safety of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (SJIA): tender 52-week data
Italian Society of Rheumatology (SIR) recommendations for performing arthrocentesis
Joint fluid aspiration, or arthrocentesis, is one of the most useful and commonly performed procedures for the diagnosis and treatment of rheumatic diseases, but to date no definite guidelines have been published. For this reason, a group of experts of the Italian Society of Rheumatology (SIR) produced evidence based recommendations for performing arthrocentesis. Among them, the most relevant are: a) arthrocentesis is necessary when synovial effusion of unknown origin is present, especially if septic or crystal arthritis is suspected; b) the patient should be clearly informed of the benefits and risks of the procedure in order to give an informed consent; c) ultrasonography should be used to facilitate arthrocentesis in difficult joints; d) fluid evacuation often has a therapeutic effect and facilitates the success of the following intraarticular injection; e) careful skin disinfection and the use of sterile, disposable material is mandatory for avoiding septic complications. Disposable, non sterile gloves should always be used by the operator, mainly for his own protection; f) contraindications are the presence of skin lesions or infections in the area of the puncture; g) the patient's anticoagulant treatment is not a contraindication, providing the therapeutic range is not exceeded; h) joint rest after arthrocentesis is not indicated. Several of these recommendations were based on experts' opinion rather than on published evidence which is scanty
Pulmonary Hypertension and Other Potentially Fatal Pulmonary Complications in Systemic Juvenile Idiopathic Arthritis
Objective Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin‐1 (IL‐1) and IL‐6 inhibitors appear to be effective treatments. Pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was to characterize and compare systemic JIA patients with these complications to a larger cohort of systemic JIA patients. Methods Systemic JIA patients who developed PAH, ILD, and/or AP were identified through an electronic Listserv and their demographic, systemic JIA, and pulmonary disease characteristics as well as their medication exposure information were collected. Patients with these features were compared to a cohort of systemic JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. Results The patients (n = 25) were significantly ( P < 0.05) more likely than the CARRA registry cohort (n = 389) to be female; have more systemic features; and have been exposed to an IL‐1 inhibitor, tocilizumab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80%) were diagnosed with pulmonary disease after 2004. Twenty patients (80%) had macrophage activation syndrome (MAS) during their disease course and 15 patients (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD. Seventeen patients (68%) were taking or recently discontinued (<1 month) a biologic agent at pulmonary symptom onset; 12 patients (48%) were taking anti–IL‐1 therapy (primarily anakinra). Seventeen patients (68%) died at a mean of 10.2 months from the diagnosis of pulmonary complications. Conclusion PAH, AP, and ILD are underrecognized complications of systemic JIA that are frequently fatal. These complications may be the result of severe uncontrolled systemic disease activity and may be influenced by medication exposure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97453/1/21889_ftp.pd
Testing the theory of immune selection in cancers that break the rules of transplantation
Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance
8.5 Predictors of long-term outcome of Juvenile Dermatomyositis (JDM): a Multicenter, Multinational Study of 490 patients
The effect of infliximab plus methotrexate on the modulation of inflammatory disease markers in juvenile idiopathic arthritis: analyses from a randomized, placebo-controlled trial
Peer reviewe
7.4 Improvements in individual disease components are sustained with long-term adalimumab therapy for polyarticular Juvenile Idiopathic Arthritis
Safety and efficacy of infliximab and adalimumab for refractory uveitis in juvenile idiopathic arthritis : 1-year followup data from the Italian Registry
To evaluate safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of juvenile idiopathic arthritis-related anterior uveitis (JIA-AU).Starting January 2007, patients with JIA-AU treated with IFX and ADA were managed by a standard protocol and data were entered into the National Italian Registry (NIR). At baseline, all patients were refractory to standard immunosuppressive treatment and/or were corticosteroid-dependent. Data recorded every 3 months included uveitis course, number/type of ocular complications, drug-related adverse events (AE), treatment change or withdrawal, and laboratory measures. Data of patients treated for at least 1 year were retrieved from the NIR and analyzed using descriptive statistics. Treatment efficacy was based on change in uveitis course and in number of ocular complications.Up to December 2009, data for 108 patients with JIA-AU treated with anti-tumor necrosis factor-\u3b1 agents were recorded in the NIR and data from 91, with at least 12 months' followup, were included in the study. Forty-eight patients were treated with IFX, 43 with ADA. Forty-seven patients (55.3%) achieved remission of AU, 28 (32.9%) had recurrent AU, and 10 (11.8%) maintained a chronic course. A higher remission rate was observed with ADA (67.4% vs 42.8% with IFX; p = 0.025). Ocular complications decreased from 0.47 to 0.32 per subject. Five patients experienced resolution of structural complications. No patient reported serious AE; 8 (8.8%) experienced 11 minor AE (9 with IFX, 2 with ADA).IFX and ADA appear to be effective and safe for treatment of refractory JIA-related uveitis, with a better performance of ADA in the medium-term period
Murine Pancreatic Adenocarcinoma Reduces Ikaros Expression and Disrupts T Cell Homeostasis
Background
Maintenance of T cell immune homeostasis is critical for adequate anti-tumor immunity. The transcription factor Ikaros is essential for lymphocyte development including T cells. Alterations in Ikaros expression occur in blood malignancies in humans and mice. In this study, we investigated the role of Ikaros in regulating T cell immune balance in pancreatic cancer mouse models.
Methodology and Principal Findings
Using our Panc02 tumor-bearing (TB) mouse model, western blot analysis revealed a reduction in Ikaros proteins while qRT-PCR showed no differences in Ikaros mRNA levels in TB splenocytes compared to control. Treatment of naïve splenocytes with the proteasomal inhibitor, MG132, stabilized Ikaros expression and prevented Ikaros downregulation by Panc02 cells, in vitro. Western blot analyses showed a reduction in protein phosphatase 1 (PP1) and protein kinase CK2 expression in TB splenocytes while CK2 activity was increased. Immunofluorescence microscopy revealed altered punctate staining of Ikaros in TB splenocytes. Flow cytometry revealed a significant decrease in effector CD4+ and CD8+ T cell percentages but increased CD4+CD25+ regulatory T cells in TB splenocytes. Similar alterations in T cell percentages, as well as reduced Ikaros and CK2 but not PP1 expression, were observed in a transgenic, triple mutant (TrM) pancreatic cancer model. Ikaros expression was also reduced in enriched TB CD3+ T cells. MG132 treatment of naïve CD3+ T cells stabilized Ikaros expression in the presence of Panc02 cells. Western blots showed reduced PP1 and CK2 expression in TB CD3+ T cells.
Conclusions/Significance
The results of this study suggest that the pancreatic tumor microenvironment may cause proteasomal degradation of Ikaros, possibly via dysregulation of PP1 and CK2 expression and activity, respectively. This loss of Ikaros expression may contribute to an imbalance in T cell percentages. Ikaros may potentially be a therapeutic target to restore T cell homeostasis in pancreatic cancer hosts, which may be critical for effective anti-tumor immunity
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