Mendelian susceptibility to mycobacterial diseases: state of the art.
IFN-γ
MSMD
Multifocal osteomyelitis
T-bet
ZNFX1
Journal
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
ISSN: 1469-0691
Titre abrégé: Clin Microbiol Infect
Pays: England
ID NLM: 9516420
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
15
12
2021
revised:
19
02
2022
accepted:
03
03
2022
pubmed:
15
3
2022
medline:
27
10
2022
entrez:
14
3
2022
Statut:
ppublish
Résumé
Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by a selective predisposition to infections caused by intracellular pathogens, such as mycobacteria, due to impaired IFN-γ immunity. To date, 18 different genes associated with MSMD have been reported. This review describes recent discoveries, a 2020-2021 update, in MSMD through the introduction of three novel genetic disorders, namely, AR IFN-γ, T-bet, and ZNFX1 complete deficiency, as well as molecular mechanisms underlying multifocal osteomyelitis in patients with this condition. PubMed databases were searched for reports of MSMD since January 2020. Relevant articles and their references were screened. The review covers a general overview, known genes, classifications, symptoms, and treatments for MSMD. MSMD is classified into two groups: isolated MSMD and syndromic MSMD. Among the 18 genes responsible, 13 cause isolated MSMD, which is characterized by selective predisposition to one or more mycobacterial and related infections, and 8 cause syndromic MSMD, which involves the combination of the mycobacterial disease infectious phenotype with additional clinical phenotypes. Among the three genetic etiologies described herein, AR IFN-γ deficiency is classified as isolated MSMD, whereas AR T-bet and ZNFX1 deficiency are classified as syndromic MSMD. Multifocal osteomyelitis is a representative symptom of MSMD, and a high frequency of multifocal osteomyelitis is reported in MSMD patients due to impaired IFN-γ responses, such as with AD IFN-γR1, AD IFN-γR2, or AD STAT1 deficiency. Impaired inhibition of osteoclast differentiation and bone resorption owing to a poor response to IFN-γ has been shown to be in association with multifocal osteomyelitis in MSMD. Over the past decade, genetic dissection by next-generation sequencing techniques has contributed to the understanding of the molecular bases of human immunity to mycobacteria. However, genetic etiologies are lacking for half of MSMD cases. Further studies will be needed to elucidate the pathogenesis of MSMD.
Sections du résumé
BACKGROUND
BACKGROUND
Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by a selective predisposition to infections caused by intracellular pathogens, such as mycobacteria, due to impaired IFN-γ immunity. To date, 18 different genes associated with MSMD have been reported.
OBJECTIVES
OBJECTIVE
This review describes recent discoveries, a 2020-2021 update, in MSMD through the introduction of three novel genetic disorders, namely, AR IFN-γ, T-bet, and ZNFX1 complete deficiency, as well as molecular mechanisms underlying multifocal osteomyelitis in patients with this condition.
SOURCES
METHODS
PubMed databases were searched for reports of MSMD since January 2020. Relevant articles and their references were screened.
CONTENT
BACKGROUND
The review covers a general overview, known genes, classifications, symptoms, and treatments for MSMD. MSMD is classified into two groups: isolated MSMD and syndromic MSMD. Among the 18 genes responsible, 13 cause isolated MSMD, which is characterized by selective predisposition to one or more mycobacterial and related infections, and 8 cause syndromic MSMD, which involves the combination of the mycobacterial disease infectious phenotype with additional clinical phenotypes. Among the three genetic etiologies described herein, AR IFN-γ deficiency is classified as isolated MSMD, whereas AR T-bet and ZNFX1 deficiency are classified as syndromic MSMD. Multifocal osteomyelitis is a representative symptom of MSMD, and a high frequency of multifocal osteomyelitis is reported in MSMD patients due to impaired IFN-γ responses, such as with AD IFN-γR1, AD IFN-γR2, or AD STAT1 deficiency. Impaired inhibition of osteoclast differentiation and bone resorption owing to a poor response to IFN-γ has been shown to be in association with multifocal osteomyelitis in MSMD.
IMPLICATIONS
CONCLUSIONS
Over the past decade, genetic dissection by next-generation sequencing techniques has contributed to the understanding of the molecular bases of human immunity to mycobacteria. However, genetic etiologies are lacking for half of MSMD cases. Further studies will be needed to elucidate the pathogenesis of MSMD.
Identifiants
pubmed: 35283318
pii: S1198-743X(22)00143-4
doi: 10.1016/j.cmi.2022.03.004
pii:
doi:
Substances chimiques
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1429-1434Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.