The long-term goal for

The long-term goal for Src inhibitor haemophilia treaters would be to have prospective predictors of inhibitor formation or avoidance; prospective predictors of immune tolerance induction

(ITI), success or failure, and to identify interventions for high-risk patients. This section briefly summarizes the background rationale for the satellite RNA sequencing (RNA seq) scientific substudy in the forthcoming NuProtect trial and how this technology may contribute to future understanding of inhibitor formation and tolerization mechanisms. There has been rapid progress in the field of genomics in the last 60 years. In 1986, the human genome project began and in 2001 the initial human genome sequence was published [10], 2 years earlier than predicted and less than 50 years since the basic structure of DNA was described [11]. Further rapid technological advance, most noteably that of next-generation sequencing (NGS), makes high throughput sequencing accessible and affordable. NGS enables genome-wide, RNA seq offering the chance to apply this exciting technology in key studies. RNA seq captures dynamic gene expression, that is which genes are actually being used or suppressed at the point of sampling. A genome-wide assessment of gene use (transcriptome Tanespimycin chemical structure analysis) will provide a snapshot of the environment of FVIII concentrate exposure in PUPs, combining genetic data reflecting both environmental factors

(inflammation, infection) and inherited genetic polymorphisms. RNA seq will be carried out in the NuProtect trial as a satellite scientific study. It will be the first study in PUPs utilizing this technology. Such a study will create a large and valuable data set for future MycoClean Mycoplasma Removal Kit research. It will be hypothesis generating, given the unselected, genome-wide recording of RNA expression data. In PUPs, 1 mL of additional blood for sequencing will be taken at baseline and every 3–4 exposure days with

routine inhibitor screening until 20 exposure days. RNA studies have been used in vaccine research to understand the mechanisms by which vaccines stimulate protective immunity. Data have enabled prediction of the immunogenicity or efficacy of vaccines and the technique has already defined predictive signatures of human antibody responses to influenza vaccination. A study by Bucasas et al. [12] investigated the correlation of gene expression patterns and antibody response to influenza vaccination in a cohort of healthy male adults. The study showed that marked-up regulation of expression of genes involved in interferon signalling, positive IL-6 regulation and antigen processing and presentation were detected early, within 24 h of vaccination. Later RNA signatures involved cellular proliferation, protein metabolism and antiapoptosis pathways. The authors concluded that high vaccine responder status correlates with increased early expression of interferon signalling and antigen processing and presentation genes.

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