Multi-Omics Analyse des Antikörpermangelsyndroms (i-PAD)

The human immune system controls how we respond to infections and other diseases. How- ever, its functioning differs substantially between individuals. Certain people have mild or severe immune defects, which makes them prone to infections, autoimmunity and cancer. Some of these immunodeficiencies are monogenetic and relatively well understood. But in many cases the molecular cause is entirely unknown, which makes these rare diseases diffi- cult to diagnose and treat. In this project, we will use cutting-edge multi-omics profiling and integrative bioinformatic analysis to dissect the molecular pathways underlying common var- iable immunodeficiency, an archetypical rare primary antibody deficiency (PAD) where im- paired B cell function causes recurrent infections. Within the i-PAD project, the lab of Chris- toph Bock at the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (http://rarediseases.at/) will focus on high-throughput profiling of chromatin accessibility and on the integrative bioinformatic analysis of all datasets.

Rare diseases are individually rare but collectively affect more than 7% of the population. These diseases are often severe, and obtaining a correct diagnosis is a key step toward adequate treatment. Patients with rare diseases are usually diagnosed based on genetic changes that negatively affect how their cells can function, but this approach does not always provide a conclusive diagnosis. Within the i-PAD project, which was funded in the ERA-NET E-Rare-3 program, the laboratory of Christoph Bock at the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases investigate epigenetic regulation in patients that cannot produce antibodies for protecting themselves against infection. This study thus looked beyond genetic changes in the DNA and investigated the epigenetic landscape of primary antibody deficiencies.