Monogenic susceptibility to live viral vaccines

Gothe, Florian; Howarth, Sophie; Duncan, Christopher J A; Hambleton, Sophie

doi:10.1016/j.coi.2021.05.006

Cited by 8 publications

(3 citation statements)

References 88 publications

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“…BCG vaccination of individuals with MSMD offers a particularly discrete example involving a bacterial pathogen ( Fekrvand et al., 2020 ). Live attenuated virus vaccinations have also been known to reveal previously undiagnosed IEI, with particularly severe consequences in individuals with SCID, as well as individuals with innate immune defects (e.g., STAT2 , IRF9 ) ( Gothe et al., 2021 ). Likewise, CARD9 deficiency underlies invasive fungal infections, primarily reported in individuals who were apparently healthy before the precipitation of their severe, and in some cases, fatal infections ( Drewniak et al., 2013 ; Rieber et al., 2016 ; Corvilain et al., 2018 ; Imanaka et al., 2021 ).…”

Section: Bodymentioning

confidence: 99%

Nature and nurture: understanding phenotypic variation in inborn errors of immunity

Similuk,

Kuijpers

2023

Front. Cell. Infect. Microbiol.

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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.

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Section: Bodymentioning

confidence: 99%

Nature and nurture: understanding phenotypic variation in inborn errors of immunity

Similuk,

Kuijpers

2023

Front. Cell. Infect. Microbiol.

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“…AR complete TYK2 deficiency impairs cellular responses to IL-12 and IL-23 more profoundly than the response to type I IFNs (Kreins et al, 2015), whereas no complete defect of JAK1 has been reported (Eletto et al, 2016). Patients with any of these four recessive inborn errors of immunity underlying a complete deficiency of cellular responses to type I IFNs are prone to various viral diseases, with AR STAT1 deficiency underlying the most diverse and severe set of viral diseases, including those caused by live attenuated virus (LAV) vaccines (Gothe et al, 2021;Poyhonen et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes

Bastard

Hsiao

Zhang

et al. 2022

Journal of Experimental Medicine

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Globally, autosomal recessive IFNAR1 deficiency is a rare inborn error of immunity underlying susceptibility to live attenuated vaccine and wild-type viruses. We report seven children from five unrelated kindreds of western Polynesian ancestry who suffered from severe viral diseases. All the patients are homozygous for the same nonsense IFNAR1 variant (p.Glu386*). This allele encodes a truncated protein that is absent from the cell surface and is loss-of-function. The fibroblasts of the patients do not respond to type I IFNs (IFN-α2, IFN-ω, or IFN-β). Remarkably, this IFNAR1 variant has a minor allele frequency >1% in Samoa and is also observed in the Cook, Society, Marquesas, and Austral islands, as well as Fiji, whereas it is extremely rare or absent in the other populations tested, including those of the Pacific region. Inherited IFNAR1 deficiency should be considered in individuals of Polynesian ancestry with severe viral illnesses.

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“…More than 10 billion doses of COVID-19 vaccines have been administered worldwide in the span of 18 months, providing an unprecedented opportunity to study and understand immunological responses and clinical reactions to vaccines. While severe adverse reactions to live-attenuated viral or bacterial vaccines have been successfully deciphered since the 1950s, with the discovery of a wide range of underlying inborn errors of immunity [ 1 , 2 ], there is currently no molecular, cellular, and immunological explanation for life-threatening reactions to any other type of vaccine. COVID-19 mRNA vaccines are very effective at preventing hypoxemic COVID-19 pneumonia.…”

mentioning

confidence: 99%

Decoding the Human Genetic and Immunological Basis of COVID-19 mRNA Vaccine-Induced Myocarditis

Bolze

Mogensen²,

Zhang³

et al. 2022

J Clin Immunol

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Monogenic susceptibility to live viral vaccines

Cited by 8 publications

References 88 publications

Nature and nurture: understanding phenotypic variation in inborn errors of immunity

Nature and nurture: understanding phenotypic variation in inborn errors of immunity

A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes

Decoding the Human Genetic and Immunological Basis of COVID-19 mRNA Vaccine-Induced Myocarditis

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