ERA-Net E-Rare

According to Cellular Pathways  Our immune system is highly personalized and it influences how well we respond to a wide range of infections and other diseases. Some people have mild or severe defects in their immune system, which makes them prone to infections, autoimmunity and cancer. Some of these defects are monogenetic and relatively well understood. But in many cases the molecular cause is entirely unknown, which makes them difficult to diagnose or to treat. In this project, we will use state-of-the-art OMICS datasets to dissect molecular pathways associated with ‘common variable immunodeficiency’ (CVID, ORPHA: #1572), an archetypical rare primary antibody deficiency (PAD) where impaired B cell function causes recurrent infections. Only a minor percentage of CVID individuals (˜25%) display monogenetic mutations. We will train our analysis pipeline on CVID patients with known monogenetic defects, to be ready to analyse samples of CVID patients with unknown genetic cause. We will also include patients with selective IgA deficiency (IgAD), which shares some clinical features with CVID and is often considered a preamble of CVID. Key leaders in CVID, immunology, genetics, epigenetics, proteomics, and bioinformatics will join forces to provide a novel and systematic classification of CVID (and IgAD) patients based on the molecular dissection of affected cellular pathways. Our approach will directly benefit PAD patients and provide a perspective for the personalized management of PAD through the use of technologies and approaches that are cost effective and ready to be used by clinical immunology experts.