Journal
SEMINARS IN IMMUNOLOGY
Volume 26, Issue 6, Pages 454-470Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.smim.2014.09.008
Keywords
BCG; Mycobacteriosis; Tuberculosis; IFN-gamma; IL-12; ISG15; Primary immunodeficiency
Categories
Funding
- INSERM
- Paris Descartes University
- Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]
- French National Research Agency (ANR) under the investments for the future program [ANR-10-IAHU-01]
- ANR grant IFNGPHOX [ANR 13-ISV-0001-01]
- National Institute of Allergy and Infectious Diseases [5R37AI095983, 5R01AI089970]
- National Center for Research Resources
- National Center for Advancing Sciences of the National Institutes of Health [8UL1TR000043]
- St. Giles Foundation
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Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, and CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-gamma-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-gamma. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-gamma-dependent immunity. (C) 2014 Elsevier Ltd. All rights reserved.
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