Genetic basis of common variable immunodeficiency: From common to variable

Common variable immunodeficiency (CVID) is one of the most prevalent primary immunodeficiencies. It is characterized by hypogammaglobulinaemia, increased susceptibility to infections and impaired vaccine responses. CVID has an important, clinical, immunological and genetic heterogeneity. A minority of patients present with monogenic forms in CVID, unlike other primary immunodeficiencies. With the development of new technologies in genetics, including next generation sequencing, the number of identified genes in CVID is increasing. Therefore, CVID is now considered as an umbrella disease, gathering distinct pathological entities. It is currently recognized that CVID is a complex polygenic rather than a monogenic syndrome. A multiomic approach combining genomics, epigenetics and proteomics will shed light on CVID complex pathophysiology, which still enigmatic. This integrative approach will also offer more targeted therapies, and therefore a personalized medicine. This review aims to discuss current knowledge concerning the genetic and molecular bases of CVID as well as their application in clinical practice.