[Genetic susceptibility to mycobacterial disease: Mendelian disorders of the interleukin-12 -interferon-gamma axis]

Rev Mal Respir. 2005 Nov;22(5 Pt 1):767-76. doi: 10.1016/s0761-8425(05)85634-7.
[Article in French]

Abstract

Introduction: Environmental non tuberculous mycobacteria and Bacillus Calmette-Guerin vaccines are weakly virulent mycobacteria. Nevertheless they may cause severe diseases in otherwise healthy children with no overt immunodeficiency. Parental consanguinity and familial forms are frequently observed among these patients, therefore this syndrome was named "Mendelian Susceptibility to Mycobacterial Disease".

State of the art: In the last nine years, fife genes have been found to be mutated in patients with this syndrome: IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1. Allelic heterogeneity accounts for ten distinct genetic disorders. Clinical phenotype differs between patients. The spectrum of disease extends from early-onset overwhelming mycobacterial infection to adult-onset localized disease and tuberculosis. Impaired IFN-gamma-mediated immunity is the common mechanism of the disease, outlining its major role in mycobacterial immunity.

Perspectives and conclusions: Better understanding of these disorders reveals an expanding clinical phenotype which justifies studying adult patients with pulmonary non tuberculous mycobacterial infection without known risk factors, severe BCGitis and recurrent tuberculosis. Molecular diagnosis makes it possible to introduce a specific regimen based on physiopathology.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Cytokines / therapeutic use
  • Genetic Predisposition to Disease*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Interleukin-12 / deficiency
  • Interleukin-12 / genetics
  • Mycobacterium Infections / genetics*
  • Mycobacterium Infections / therapy
  • Receptors, Interferon / deficiency
  • Receptors, Interferon / genetics
  • Receptors, Interleukin / deficiency
  • Receptors, Interleukin / genetics

Substances

  • Anti-Bacterial Agents
  • Cytokines
  • Receptors, Interferon
  • Receptors, Interleukin
  • Interleukin-12
  • Interferon-gamma