ABSTRACT
Primary immune deficiency diseases (PIDDs), recognized more than 50 years ago, have provided unique opportunities to study the cellular, biochemical and molecular events that are involved in the function of a normal immune system. The discovery in recent years of single genes responsible for specific immunodeficiency disorders, and the understanding of the function of the products of these genes, have changed our approach from the descriptive to the molecular level, and have provided new tools to redefine genetic diseases of the immune system in molecular terms. We are now in a position to confirm the suspected diagnosis of a molecularly defined PIDD at the gene level, to recognize different clinical phenotypes resulting from mutations of the same gene and, conversely, to understand why a particular clinical phenotype can be caused by mutations of a number of different genes. The understanding of the molecular basis of PIDDs will allow us to design new and more effective therapeutic strategies. Finally, genetically determined PIDD are ‘experiments of nature’ that provide insight into the molecular events that are crucial and non-redundant for an effective cognate immune system. In this review, we use ‘entities of function’ to catalog the most common prototypes of PIDD, addressing both the cognate and innate immune systems (Table 1).
