Characterisation of the genetic and immunological factors controlling appropriate responses to infections in children

Primary immune-deficiencies (PIDs) constitute a growing group of inherited disorders characterized by defects in the immune system. PID typically results in increased susceptibility to infection. We hypothesize that PID is a major cause of life-threatening infections in previously healthy children. The clinical and immunological phenotype of previously healthy children with life-threatening infections will be fully elaborated. Whole exome sequencing will be performed and candidate variants studied at the functional and gene level using state-of-the-art technology: e.g. CrispR-Cas and differentiated induced pluripotent stem cell technology. Moreover, we will study the factors that dictate the response to vaccinations in children, and whether these same factors determine the outcome of natural infections .