Nature and nurture: understanding phenotypic variation in inborn errors of immunity.
environment
genetics
inborn error of immunity
penetrance
phenotypic variation
time
Journal
Frontiers in cellular and infection microbiology
ISSN: 2235-2988
Titre abrégé: Front Cell Infect Microbiol
Pays: Switzerland
ID NLM: 101585359
Informations de publication
Date de publication:
2023
2023
Historique:
received:
09
03
2023
accepted:
17
08
2023
medline:
3
10
2023
pubmed:
2
10
2023
entrez:
2
10
2023
Statut:
epublish
Résumé
The overall disease burden of pediatric infection is high, with widely varying clinical outcomes including death. Among the most vulnerable children, those with inborn errors of immunity, reduced penetrance and variable expressivity are common but poorly understood. There are several genetic mechanisms that influence phenotypic variation in inborn errors of immunity, as well as a body of knowledge on environmental influences and specific pathogen triggers. Critically, recent advances are illuminating novel nuances for fundamental concepts on disease penetrance, as well as raising new areas of inquiry. The last few decades have seen the identification of almost 500 causes of inborn errors of immunity, as well as major advancements in our ability to characterize somatic events, the microbiome, and genotypes across large populations. The progress has not been linear, and yet, these developments have accumulated into an enhanced ability to diagnose and treat inborn errors of immunity, in some cases with precision therapy. Nonetheless, many questions remain regarding the genetic and environmental contributions to phenotypic variation both within and among families. The purpose of this review is to provide an updated summary of key concepts in genetic and environmental contributions to phenotypic variation within inborn errors of immunity, conceptualized as including dynamic, reciprocal interplay among factors unfolding across the key dimension of time. The associated findings, potential gaps, and implications for research are discussed in turn for each major influencing factor. The substantial challenge ahead will be to organize and integrate information in such a way that accommodates the heterogeneity within inborn errors of immunity to arrive at a more comprehensive and accurate understanding of how the immune system operates in health and disease. And, crucially, to translate this understanding into improved patient care for the millions at risk for serious infection and other immune-related morbidity.
Identifiants
pubmed: 37780853
doi: 10.3389/fcimb.2023.1183142
pmc: PMC10538643
doi:
Types de publication
Journal Article
Review
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1183142Informations de copyright
Copyright © 2023 Similuk and Kuijpers.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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