Send to

Choose Destination
Crit Rev Clin Lab Sci. 2018 May;55(3):184-204. doi: 10.1080/10408363.2018.1444580. Epub 2018 Mar 4.

Laboratory evaluation of the IFN-γ circuit for the molecular diagnosis of Mendelian susceptibility to mycobacterial disease.

Author information

a Allergy and Clinical Immunology Department , Hospital Sant Joan de Déu, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu , Barcelona , Spain.
b Functional Unit of Clinical Immunology , Hospital Sant Joan de Déu-Hospital Clinic , Barcelona , Spain.
c Department of Immunology , Hospital Universitario de Gran Canaria Dr. Negrín , Las Palmas de Gran Canaria , Spain.
d Laboratory of Human Genetics of Infectious Diseases, Necker Branch , INSERM-U1163 , Paris , France.
e Imagine Institute, Paris Descartes University , Paris , France.
f St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University , New York , NY , USA.
g Pediatric Infectious Disease and Immunodeficiency Unit , Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron , Barcelona , Spain.
h Immunology Department , Biomedical Diagnostics Center, Hospital Clinic-IDIBAPS , Barcelona , Spain.
i Pediatric Hematology-Immunology Unit , Necker Hospital for Sick Children , Paris , France.
j Howard Hughes Medical Institute , New York , NY , USA.
k Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP , Paris , France.


The integrity of the interferon (IFN)-γ circuit is necessary to mount an effective immune response to intra-macrophagic pathogens, especially Mycobacteria. Inherited monogenic defects in this circuit that disrupt the production of, or response to, IFN-γ underlie a primary immunodeficiency known as Mendelian susceptibility to mycobacterial disease (MSMD). Otherwise healthy patients display a selective susceptibility to clinical disease caused by poorly virulent mycobacteria such as BCG (bacille Calmette-Guérin) vaccines and environmental mycobacteria, and more rarely by other intra-macrophagic pathogens, particularly Salmonella and M. tuberculosis. There is high genetic and allelic heterogeneity, with 19 genetic etiologies due to mutations in 10 genes that account for only about half of the patients reported. An efficient laboratory diagnostic approach to suspected MSMD patients is important, because it enables the establishment of specific therapeutic measures that will improve the patient's prognosis and quality of life. Moreover, it is essential to offer genetic counseling to affected families. Herein, we review the various genetic and immunological diagnostic approaches that can be used in concert to reach a molecular and cellular diagnosis in patients with MSMD.


MSMD; Mycobacteria; diagnosis; interferon gamma; intracellular pathogens; primary immunodeficiency

[Available on 2019-05-01]

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center