Project description:PFAPA, the syndrome of periodic fever associated with aphthous stomatitis, pharyngitis and/or cervical adenitis, is the most common periodic fever disease in children. Cases are mostly sporadic; the etiopathogenesis is unknown. In order to shed more insights into pathogenesis, we performed microarray expression analysis on samples from patients with PFAPA during and between flares, healthy controls and patients with hereditary autoinflammatory diseases during flares. RNA was extracted from whole peripheral blood from six patients with PFAPA syndrome during flares and asymptomatic intervals, six healthy controls and six patients with hereditary autoinflammatory diseases (2 familial Mediterranean fever (FMF), 1 TNF-receptor-asociated periodic fever syndrome (TRAPS) and 3 cryopyrin-associated periodic syndromes (CAPS)).
Project description:PFAPA, the syndrome of periodic fever associated with aphthous stomatitis, pharyngitis and/or cervical adenitis, is the most common periodic fever disease in children. Cases are mostly sporadic; the etiopathogenesis is unknown. In order to shed more insights into pathogenesis, we performed microarray expression analysis on samples from patients with PFAPA during and between flares, healthy controls and patients with hereditary autoinflammatory diseases during flares.
Project description:Current diagnostic methods used to evaluate patients with pharyngitis for the presence of group A Streptococcus (GAS) do not discriminate between acute infection and asymptomatic carriage, potentially resulting in overuse of antibiotics. Host response as measured by the transcriptomic profile of peripheral blood leukocytes could make this distinction, and could also distinguish between GAS and viral infection. We used RNA sequencing to generate transcriptomes from whole blood samples from 37 children, including 10 with acute GAS pharyngitis, 5 asymptomatic GAS carriers, 3 with adenoviral pharyngitis, 3 with pharyngitis of unknown etiology, and 16 asymptomatic children negative for GAS. Transcriptional profiles from each group were distinct . 1357 genes were upregulated in the children with symptomatic GAS compared to those with asymptomatic carriage. A panel of 13 genes distinguished between children with acute GAS and all others with 91% accuracy. The gene encoding CD177, a marker of neutrophil activation, was markedly overexpressed in children with acute GAS and has potential as a diagnostic biomarker. We conclude that measurement of host response is highly promising to improve the diagnosis of GAS pharyngitis and could help limit unnecessary antibiotic use.
Project description:Objective. To evaluate the efficacy and safety of canakinumab treatment in active hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). Methods. This is a 3-part open-label study with a 6-month treatment period (P1; 300 mg or 4 mg/kg q6w) a 6-month withdrawal period (P2) and a 24-month treatment period (P3). The primary endpoint was reduction in frequency of flares during treatment period compared with the historical period (HP; period in which patients did not receive drugs other than NSAIDs and/or steroids).
Project description:Background Deciphering host responses contributing to dengue shock syndrome (DSS), the life-threatening form of acute viral dengue infections, is required to improve both the differential prognosis and the treatments provided to DSS patients, a challenge for clinicians. Methodology/Principal Findings Based on a prospective study, we analyzed the genome-wide expression profiles of whole blood cells from 48 matched Cambodian children: 19 progressed to DSS while 16 and 13 presented respectively classical dengue fever (DF) or dengue hemorrhagic fever grades I/II (DHF). Using multi-way analysis of variance (ANOVA) and adjustment of p-values to control the False Discovery Rate (FDR<10%), we identified a signature of 2959 genes differentiating DSS patients from both DF and DHF, and showed a strong association of this DSS-gene signature with the dengue disease phenotype. Using a combined approach to analyse the molecular patterns associated with the DSS-gene signature, we provide an integrative overview of the transcriptional responses altered in DSS children. In particular, we show that the transcriptome of DSS children blood cells is characterized by a decreased abundance of transcripts related to T and NK lymphocyte responses and by an increased abundance of anti-inflammatory and repair/remodeling transcripts. We also show that unexpected pro-inflammatory gene patterns at the interface between innate immunity, inflammation and host lipid metabolism, known to play pathogenic roles in acute and chronic inflammatory diseases associated with systemic vascular dysfunction, are transcriptionnally active in the blood cells of DSS children. Conclusions/Significance We provide a global while non exhaustive overview of the molecular mechanisms altered in of DSS children and suggest how they may interact to lead to final vascular homeostasis breakdown. We suggest that some mechanisms identified should be considered putative therapeutic targets or biomarkers of progression to DSS. Whole blood genome-wide expression profiles of Cambodian children (3-15 year old) infected with dengue virus, having different clinical outcomes were compared. The studied cohort included 16 acute dengue fever samples, 13 acute dengue hemorrhagic fever samples and 19 acute dengue shock syndrome samples, classified according to the 1997 WHO criteria and randomised for age, gender, viral serotype and day of blood sampling after onset of fever. Microarray data were normalised using the quantile method. Multi-way ANOVA was used to compared the three clinical groups, at several False Discovery Rate of 10. Unsupervised Hierarchical Clustering (TreeView) showed that DSS patients clustered together (17 out of 19), identifying a gene-signature of DSS. Bio-informatics-based analysis using the demonstration version 7.1 of Ingenuity Pathway Analysis software (IPA; Ingenuity Systems, www.ingenuity.com) associated with manual and litterature-based analysis was carried out to identify the most relevant functional processes associated with the identified DSS gene expression profile. This was done by combining most informative canonical pathways identified using IPA, genes having the strongest association with the disease phenotype based on ANOVA analysis, and similarities to molecular patterns altered in other systemic inflammatory processes associated with endothelial dysfunction.
Project description:We were able to obtain distinct gene expression profile between children with typhoid fever and other bacteremic infections. Peripheral blood of Nigerian children with typhoid fever and other bacteremic infection were obtained in Paxgene tubes. Total RNa were extracted using Paxgene blood RNA kit and 4x44K (G4112F) human GE array were processed according to standard Agilent procedures