The cup runneth over: lessons from the ever-expanding pool of primary immunodeficiency diseases

Nat Rev Immunol. 2013 Sep;13(9):635-48. doi: 10.1038/nri3493. Epub 2013 Jul 26.


A recent surge in newly described primary immunodeficiencies (PIDs) has highlighted new physiological and pathophysiological pathways that affect the immune system. Furthermore, the study of individuals with PIDs has substantially improved our understanding of basic cellular and signalling pathways in host defence and immune regulation. Single-gene defects can lead to disease manifestations that range from extremely narrow infectious phenotypes to remarkably broad multisystem effects. Hypomorphic or hypermorphic gene mutations often occur in human diseases; when coupled with the fact that humans are exposed to naturally encountered antigens and pathogens, this helps to make the case that the study of immunological diseases in humans should be at the forefront of basic immunological research.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Cytokines / immunology
  • Humans
  • Immunity, Humoral / genetics
  • Immunity, Humoral / immunology
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology*
  • Mutation


  • Cytokines