Immunodeficiency and disorders of immune dysregulation

The spectrum of clinical features associated with primary immune deficiency disorders (PIDs) has broadened due to the recent identification of many novel causative genes. Patients present with increased susceptibility to infections in addition to significant immune dysregulation, often leading to multiple autoimmunity, lymphoproliferation, and malignancy. Immunosuppressive treatment is often required but has to be weighed against augmented infectious risk. Recently, the improved molecular understanding of the mechanisms underlying many loss-of-function (LOF) and gain-of-function (GOF) genetic defects leading to PIDs has set the ground for the development of mechanism-based therapeutic strategies that target a specific cell function. This article describes the clinical and laboratory features of selected recently described PIDs associated with immune dysregulation and novel precision medicine strategies aimed to control the disease burden in affected patients.