Human primary immunodeficiencies causing defects in innate immunity

Curr Opin Allergy Clin Immunol. 2013 Dec;13(6):607-13. doi: 10.1097/ACI.0000000000000010.


Purpose of review: There have been exciting recent advances in identifying new mutations that cause human primary immunodeficiencies which impact innate immune defences. In this review, we will highlight the most important and influential advances published in the last 18 months related to the defects of the innate immune system. We will also provide clinical context to facilitate the incorporation of these discoveries into clinical practice.

Recent findings: We will specifically focus on three areas that have seen recent significant advances: defects in Toll-like receptor signalling that enhance susceptibility to viral infection, particularly herpes simplex encephalitis; defects in innate immunity that impact phagocyte function predisposing to mycobacterial infection; and the discovery of genes responsible for isolated congenital asplenia.

Summary: The field of innate immunodeficiency has benefited greatly from the recent improvements in genome sequencing technology and has advanced dramatically in the last 18 months. For clinicians confronted with patients with suspected innate immunodeficiency, these new discoveries not only increase the likelihood that a patient will receive a specific molecular diagnosis and tailored therapy, but also add significant complexity to the diagnostic workup. Future challenges will include identifying accurate, cost-effective diagnostic approaches to these novel immunodeficiencies, so these impressive advances in our understanding of innate immunity can be translated into improved health outcomes for our affected patients and their families.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Common Variable Immunodeficiency*
  • Encephalitis, Herpes Simplex / genetics
  • Encephalitis, Herpes Simplex / immunology
  • Encephalitis, Herpes Simplex / pathology
  • Encephalitis, Herpes Simplex / physiopathology
  • Genetic Predisposition to Disease
  • Humans
  • Immunity, Innate / genetics*
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / pathology
  • Immunologic Deficiency Syndromes / physiopathology
  • Mycobacterium Infections / genetics
  • Mycobacterium Infections / immunology
  • Mycobacterium Infections / pathology
  • Mycobacterium Infections / physiopathology
  • Phagocytes* / immunology
  • Phagocytes* / pathology
  • Primary Immunodeficiency Diseases
  • Spleen / abnormalities
  • Spleen / immunology
  • Spleen / pathology
  • Spleen / physiopathology
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology


  • Toll-Like Receptors

Supplementary concepts

  • Splenic Hypoplasia