ABSTRACT: Gene expression data of whole blood of systemic juvenile idiopathic arthritis (SJIA) patients treated with canakinumab or placebo and age matched healthy controls
Project description:Gene expression profiling of peripheral blood cells from patients with rheumatoid arthritis (RA)/ systemic lupus erythematosus (SLE)/ polyarticular type juvenile idiopathic arthritis (polyJIA)/ systemic-onset JIA (sJIA) vs healthy children (HC) and healthy individual (HI).
Project description:Biomarker identification for diagnosis of systemic juvenile idiopathic arthritis (SJIA), an auto-inflammatory disease that presents with prolonged fevers. Disease vs. healthy control
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.
Project description:Biomarker identification for diagnosis of systemic juvenile idiopathic arthritis (SJIA), an auto-inflammatory disease that presents with prolonged fevers.
Project description:Gene expression data of whole blood of systemic juvenile idiopathic arthritis (SJIA) patients treated with canakinumab or placebo and age matched healthy controls
Project description:Systemic juvenile idiopathic arthritis (SJIA) confers high risk for macrophage activation syndrome (MAS), a life-threatening episode of hyperinflammation driven by IFN-γ. Monocytes in SJIA display IFNγ-hyperresponsiveness, but the molecular basis of this remains unclear. The objective of this study is to identify circulating monocyte polarization phenotypes including features of interferon response. Bulk RNA-seq of purified monocytes was performed on healthy controls as well as patients with inactive SJIA (satisfy Wallace criteria for clinically inactive disease), active SJIA, new-onset SJIA (NOS), and macrophage activation syndrome (2016 MAS Classification Criteria). We observed marked transcriptional changes in patients with elevated ferritin levels. We also identified substantial overlap with multiple polarization states but little evidence of IFN-induced signature.
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.
Project description:Objective. Previous observations suggest that active systemic juvenile idiopathic arthritis (sJIA) is associated with a prominent erythropoiesis gene expression signature. The aim of this study was to determine the association of this signature with peripheral blood mononuclear cell (PBMC) subpopulations and its specificity for sJIA as compared to related conditions. 125 patients with JIA (18 sJIA and 107 non-sJIA) and 29 controls were studied. PBMC were isolated and analyzed for multiple surface antigens by flow cytometry and for gene expression profiles. The proportions of different PBMC subpopulations were compared among sJIA, non-sJIA patients and controls and subsequently correlated with the strength of the erythropoiesis signature. Additional gene expression data from patients with familial hemophagocytic lymphohistiocytosis (FHLH) and from a published sJIA cohort were analyzed to determine if the erythropoiesis signature was present. Keywords: Patient Vs Control, reassassment of phenotype Peripheral blood samples were obtained from 29 healthy children and 125 children with JIA . RNA was purified from Ficoll-isolated mononuclear cells, fluorescently labeled and then hybridized to Affymetrix U133 Plus 2.0 GeneChips. Data were analyzed using ANOVA at a 5% false discovery rate threshold after Robust Multi-Array Average pre-processing and Distance Weighted Discrimination normalization.
Project description:Systemic Juvenile Idiopathic Arthritis (sJIA) has been strongly associated with macrophage activation syndrome (MAS). To better understand the pathogenesid of sJIA and to facilitate the search for MAS biomarkers, we examine gene expression profiles in untreated new onset sJIA. 17 new onset sJIA patients were included in the study. 5 of the 17 patients showed evidence of subclinical MAS and 2 eventually developed overt MAS. Keywords: disease versus control
Project description:This study investigated neutrophils in systemic onset Juvenile Idiopathic Arthritis (sJIA), one of the most common multifactorial autoinflammatory diseases, characterized by arthritis and severe systemic inflammatory manifestations like fever, rash, hepatosplenomegaly and serositis. Neutrophil counts were markedly increased at disease onset, correlated to levels of inflammatory mediators and normalized within days after initiation of therapy with recombinant IL-1 receptor antagonist (rIL-1RA). Neutrophils isolated from 3 sJIA patients with active disease, before initiation of therapy (2 disease onset, 1 systemic flare) and 3 healthy controls were compared. A clear separation between the transcriptome of sJIA patients and HCs was observed. In total, 1068 genes were significantly upregulated and 625 genes were downregulated in sJIA; GO-analyses indicated upregulation of inflammatory processes in sJIA neutrophils compared to HCs. GSEA analyses revealed a significant enrichment with the transcriptome of neutrophils in sepsis patients. Correspondingly, neutrophils from sJIA patients during active disease displayed a primed phenotype characterized by an increased respiratory burst, CD62L shedding and degranulation of secretory vesicles. This phenotype was completely reversed in sJIA patients in remission on rIL-1RA. Our data show an important role for neutrophils in the early inflammatory phase of sJIA and a strong susceptibility of neutrophil numbers and inflammatory activity to IL-1 signaling blockade.
