Canakinumab treatment in hyperimmunoglobulinemia D with periodic fever syndrome
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE97075 | GEO | 2018/09/17
REPOSITORIES: GEO
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Project description:Background: Blocking the action of the pro-inflammatory cytokine interleukin-1 (IL-1) reduces beta-cell secretory dysfunction and apoptosis in vitro, diabetes incidence in animal models of Type 1 diabetes mellitus (T1D), and glycaemia via improved beta-cell function in patients with T2D. We hypothesised that canakinumab, a monoclonal antibody to IL-1B, improves beta-cell function in patients with new-onset T1D. Methods: In an individually randomised, two-group parallel trial involving 12 sites in US, 69 patients aged 6-45 with T1D, < 12 weeks of symptoms, and assigned by centralised computer-generated blocked randomisation with locked computer-file concealment to treatment with 2 mg/kg (maximum 300 mg) canakinumab (n=45) or placebo (n=22) monthly for 12 months as add-on to conventional therapy. Participants and care-givers, but not data monitoring unit, were masked to group assignment. The primary end-point was change in the two-hour area-under-the-curve C-peptide response to MMT 12 months.
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Project description:Canakinumab is a human anti-interleukin-1 beta (IL-1 beta) monoclonal antibody neutralizing IL-1 beta. Systemic juvenile idiopathic arthritis (SJIA) is a rare, multigenic, autoinflammatory disease of unknown etiology characterized by chronic arthritis; intermittent high-spiking fever, rash, and elevated levels of acute-phase reactants. Blood samples of SJIA patients were obtained from two phase 3 clinical trials conducted by the members of the Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG) (Clinicaltrials.gov: NCT00886769 and NCT00889863). For patients, baseline and day 3 samples were analyzed for either placebo or canakinumab (Ilaris) treatment. Clinical response was assessed at day 15 using adapted JIA American College of Rheumatology (ACR) response criteria. Overall, 206 samples were used in this study including 22 samples from healthy controls, 33 samples of placebo treated patients and 151 samples of canakinumab treated patients.
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Project description:Nonsteroidal anti-inflammatory drugs (NSAIDs) has been suggested as adjunctive anti-tumor agents in human and veterinary medicine. However, its anti-tumor molecular machinery is still controversial. Therefore, we performed whole transcriptome analysis to discover gene expression influenced by NSAIDs treatment. A canine melanoma cell line (Mi/CMM1) was treated by three NSAIDs, piroxicam, carprofen, and robenacoxib, at their half maximal (50%) inhibitory concentrations (116 µM, 779 µM, and 156 µM) for 6 hours. Subsequently, total RNA were extracted and microarray analysis was performed to evaluate change in gene expression caused by NSAIDs treatment. Each condition had three biological replicates.
2016-03-09 | E-GEOD-78988 | biostudies-arrayexpress
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Project description:Innate immune system represents the ancestral defense against infectious agents preserved along the evolution and species; it is phylogenetically older than the adaptive immune system, which exists only in the vertebrates. Cells with phagocytic activity such as neutrophils, macrophages, and natural killer (NK) cells play a key role in innate immunity. In 1999 Kastner et al. first introduced the term "autoinflammation" describing two diseases characterized by recurrent episodes of systemic inflammation without any identifiable infectious trigger: Familial Mediterranean Fever (FMF) and TNF Receptor Associated Periodic Syndrome (TRAPS). Autoinflammatory diseases (AIDs) are caused by self-directed inflammation due to an alteration of innate immunity leading to systemic inflammatory attacks typically in an on/off mode. In addition to inflammasomopathies, nuclear factor (NF)-?B-mediated disorders (also known as Rhelopathies) and type 1 interferonopathies are subjects of more recent studies. This review aims to provide an overview of the field with the most recent updates (see "Most recent developments in.." paragraphs) and a description of the newly identified AIDs.
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