Immunological and genetic bases of new primary immunodeficiencies

Since 1952, when congenital agammaglobulinaemia was described by Bruton, the characterization of genetically defined immunodeficiencies in humans has been crucial for a better understanding of the biology of the innate and adaptive immune responses. This Review focuses on the characterization of new primary immunodeficiencies and disease-related genes. A series of primary defects of innate immunity have recently been discovered and are discussed here. Moreover, new defects in pre-B-cell and B-cell differentiation and antibody maturation are summarized and recently discovered monogenic immunodeficiencies that disturb the homeostasis of both the innate and the adaptive immune systems are discussed.