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The evolving story of human leukocyte antigen and the immunogenetics of peanut allergy.

ABSTRACT: Peanut allergy (PA) clearly has a heritable component. Specific genetic contributions are unknown, but human leukocyte antigen (HLA) loci are obvious candidates. This review focuses on emerging studies of HLA associations with PA.PubMed was searched with no time limitations using key terms human leukocyte antigen, HLA, MHC, peanut, peanut hypersensitivity, and peanut allergy.Qualifying studies were English-language reports of genetic analyses examining PA and HLA associations.Seven relevant citations were identified, which were published from 1996 to 2015. Early studies using candidate gene approaches found associations between PA and HLA-DR and -DQ alleles (HLA-DRB1*08 and DQB1*06:03P) when comparing subjects with peanut allergy with nonallergic unrelated control groups. No significant associations were found between siblings with and without peanut allergy. However, a recent large genomewide association study of patients with peanut allergy and their family members found 2 PA-associated single-nucleotide polymorphisms (rs9275596 and rs7192) mapping to regions involving the HLA-DR and HLA-DQ genes. Associations with differential DNA methylation partly mediated the associations between PA and single-nucleotide polymorphisms.Early studies using candidate gene approaches identified HLA associations with PA compared with the general population, suggesting a link with atopy but failing to identify a PA-specific association. These studies had various limitations that included small samples. The most compelling evidence for a PA-specific HLA association comes from a genomewide association study, which examined the entire genome in large, well-defined, related cohorts. More research is needed to validate and replicate these findings, to perform fine genetic mapping of specific HLA loci, and to demonstrate underlying mechanisms of HLA contributions to PA.

SUBMITTER: Hemler JA

PROVIDER: S-EPMC5665015 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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The evolving story of human leukocyte antigen and the immunogenetics of peanut allergy.

Hemler Jonathan A JA Phillips Elizabeth J EJ Mallal Simon A SA Kendall Peggy L PL

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 20151027 6

<h4>Objective</h4>Peanut allergy (PA) clearly has a heritable component. Specific genetic contributions are unknown, but human leukocyte antigen (HLA) loci are obvious candidates. This review focuses on emerging studies of HLA associations with PA.<h4>Data sources</h4>PubMed was searched with no time limitations using key terms human leukocyte antigen, HLA, MHC, peanut, peanut hypersensitivity, and peanut allergy.<h4>Study selections</h4>Qualifying studies were English-language reports of geneti ...[more]

PMID: 26522257

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Project description:BackgroundThe prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut consumption and avoidance to determine which strategy is most effective in preventing the development of peanut allergy in infants at high risk for the allergy.MethodsWe randomly assigned 640 infants with severe eczema, egg allergy, or both to consume or avoid peanuts until 60 months of age. Participants, who were at least 4 months but younger than 11 months of age at randomization, were assigned to separate study cohorts on the basis of preexisting sensitivity to peanut extract, which was determined with the use of a skin-prick test--one consisting of participants with no measurable wheal after testing and the other consisting of those with a wheal measuring 1 to 4 mm in diameter. The primary outcome, which was assessed independently in each cohort, was the proportion of participants with peanut allergy at 60 months of age.ResultsAmong the 530 infants in the intention-to-treat population who initially had negative results on the skin-prick test, the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group and 1.9% in the consumption group (P<0.001). Among the 98 participants in the intention-to-treat population who initially had positive test results, the prevalence of peanut allergy was 35.3% in the avoidance group and 10.6% in the consumption group (P=0.004). There was no significant between-group difference in the incidence of serious adverse events. Increases in levels of peanut-specific IgG4 antibody occurred predominantly in the consumption group; a greater percentage of participants in the avoidance group had elevated titers of peanut-specific IgE antibody. A larger wheal on the skin-prick test and a lower ratio of peanut-specific IgG4:IgE were associated with peanut allergy.ConclusionsThe early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00329784.).

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The evolving story of human leukocyte antigen and the immunogenetics of peanut allergy.

Publications

The evolving story of human leukocyte antigen and the immunogenetics of peanut allergy.

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