Pediatric anaphylaxis and hyper IgE syndrome

Dosanjh, Amrita

doi:10.2147/jaa.s129160

Cited by 4 publications

(2 citation statements)

References 4 publications

(9 reference statements)

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“…We suggest that measurement of allergen-specific IgE more accurately reflects atopy than total IgE or basal IgE, which have not consistently been associated with anaphylaxis or food allergy. 30 Using CRISPR-targeted knockout/replacement alleles or published, available knockout alleles, we validated the effects of mutations in 23 (74%) of the 31 genes; the effects of eight mutations (26%) were not validated. Many of the validated genes aligned to signaling pathways important for the production of IgE.…”

Section: Discussionmentioning

confidence: 99%

“…Including Lck, Prkcb, Sharpin, and Nfkb1 , we investigated 32 mutations in 31 genes for their effects on the quantity of serum papain‐specific IgE or IgG1 produced in response to immunization. We suggest that measurement of allergen‐specific IgE more accurately reflects atopy than total IgE or basal IgE, which have not consistently been associated with anaphylaxis or food allergy 30 . Using CRISPR‐targeted knockout/replacement alleles or published, available knockout alleles, we validated the effects of mutations in 23 (74%) of the 31 genes; the effects of eight mutations (26%) were not validated.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Dominant atopy risk mutations identified by mouse forward genetic analysis

SoRelle

Chen

Wang

et al. 2020

Allergy

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Background Atopy, the overall tendency to become sensitized to an allergen, is heritable but seldom ascribed to mutations within specific genes. Atopic individuals develop abnormally elevated IgE responses to immunization with potential allergens. To gain insight into the genetic causes of atopy, we carried out a forward genetic screen for atopy in mice. Methods We screened mice carrying homozygous and heterozygous N‐ethyl‐N‐nitrosourea (ENU)–induced germline mutations for aberrant antigen‐specific IgE and IgG1 production in response to immunization with the model allergen papain. Candidate genes were validated by independent gene mutation. Results Of 31 candidate genes selected for investigation, the effects of mutations in 23 genes on papain‐specific IgE or IgG1 were verified. Among the 20 verified genes influencing the IgE response, eight were necessary for the response, while 12 repressed IgE. Nine genes were not previously implicated in the IgE response. Fifteen genes encoded proteins contributing to IgE class switch recombination or B‐cell receptor signaling. The precise roles of the five remaining genes (Flcn, Map1lc3b, Me2, Prkd2, and Scarb2) remain to be determined. Loss‐of‐function mutations in nine of the 12 genes limiting the IgE response were dominant or semi‐dominant for the IgE phenotype but did not cause immunodeficiency in the heterozygous state. Using damaging allele frequencies for the corresponding human genes and in silico simulations (Monte Carlo) of undiscovered atopy mutations, we estimated the percentage of humans with heterozygous atopy risk mutations. Conclusions Up to 37% of individuals may be heterozygous carriers for at least one dominant atopy risk mutation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%