Whole blood transcriptomics identifies gene expression associated with peanut allergy in infants at high risk.
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ABSTRACT:
SUBMITTER: Devonshire AL
PROVIDER: S-EPMC9290487 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.).
| S-EPMC4416404 | biostudies-literature
Project description:BACKGROUND:Prognostication of peanut allergy (PNA) is relevant for early interventions. We aimed to determine baseline parameters associated with the development of PNA in 3- to 15-month-olds with likely egg and/or milk allergy, and/or moderate to severe atopic dermatitis (AD) and a positive egg/milk skin prick test (SPT), but no known PNA. METHODS:The primary endpoint was PNA [confirmed/convincing diagnosis or last classified as serologic PNA (<2 years, ?5 kUA/L, otherwise ?14 kUA/L, peanut IgE)] among 511 participants (median follow-up, 7.3 years). Associations were explored with univariate logistic regression; factors with P < 0.15 were analyzed by stepwise multiple logistic regression, using data stratified by PNA status and randomly assigned to development and validation datasets. RESULTS:205/511 (40.1%) had PNA. Univariate factors associated with PNA (P < 0.01) included increased AD severity, larger egg and peanut SPT, greater egg, milk, peanut, Ara h1-h3 IgE, higher peanut IgG and IgG4, and increased pregnancy peanut consumption. P-values were between 0.01 and 0.05 for younger age, non-white race, lack of breastfeeding, and increased lactation peanut consumption. Using a development dataset, the multivariate model identified younger age at enrollment, greater peanut and Ara h2 IgE, and lack of breastfeeding as prognosticators. The final model predicted 79% in the development and 75% in the validation dataset (AUC = 0.83 for both). Models using stricter or less strict PNA criteria both found Ara h2 as predictive. CONCLUSIONS:Key factors associated with PNA in this high-risk population included lack of breastfeeding, age, and greater Ara h2 and peanut-specific IgE, which can be used to prognosticate outcomes.
| S-EPMC6817376 | biostudies-literature
Project description:Peanut allergy is an IgE-mediated, persisting immune disorder that is of major concern worldwide. Currently, no routine immunotherapy is available to treat this often severe and sometimes fatal food allergy. Traditional subcutaneous allergen immunotherapy with crude peanut extracts has proven not feasible due to the high risk of severe systemic side effects. The allergen-specific approaches under preclinical and clinical investigation comprise subcutaneous, oral, sublingual and epicutaneous immunotherapy with whole-peanut extracts as well as applications of hypoallergenic peanut allergens or T cell epitope peptides. Allergen-nonspecific approaches include monoclonal anti-IgE antibodies, TCM herbal formulations and Toll-like receptor 9-based immunotherapy. The potential of genetically engineered plants with reduced allergen levels is being explored as well as the beneficial influence of lactic acid bacteria and soybean isoflavones on peanut allergen-induced symptoms. Although the underlying mechanisms still need to be elucidated, several of these strategies hold great promise. It can be estimated that individual strategies or a combination thereof will result in a successful immunotherapy regime for peanut-allergic individuals within the next decade.
| S-EPMC5548240 | biostudies-other
Project description:ImportanceEarly peanut introduction reduces the risk of developing peanut allergy, especially in high-risk infants. Current US recommendations endorse screening but are not cost-effective relative to other international strategies.ObjectiveTo identify scenarios in which current early peanut introduction guidelines would be cost-effective.Design, setting, and participantsThis simulation/cohort economic evaluation used microsimulations and cohort analyses in a Markov model to evaluate the cost-effectiveness of early peanut introduction with and without peanut skin prick test (SPT) screening in high-risk infants during an 80-year horizon from a societal perspective. Data were analyzed from April to May 2019.ExposuresHigh-risk infants with early-onset eczema and/or egg allergy underwent early peanut introduction with and without peanut SPT screening (100?000 infants per treatment strategy) using a dichotomous 8-mm SPT cutoff value (stipulated in the current US guideline).Main outcomes and measuresCost, quality-adjusted life-years (QALYs), net monetary benefit, peanut allergic reactions, severe allergic reactions, and deaths due to peanut allergy.ResultsIn the simulated cohort of 200 000 infants and using the base case during the model horizon, a no-screening approach had lower mean (SD) costs ($13?449 [$38?163] vs $15?279 [$38?995]) and higher mean (SD) gain in QALYs (29.25 [3.28] vs 29.23 [3.30]) vs screening but resulted in more allergic reactions (mean [SD], 1.07 [3.15] vs 1.01 [3.02]), severe allergic reactions (mean [SD], 0.53 [1.66] vs 0.52 [1.62]), and anaphylaxis involving cardiorespiratory compromise (mean [SD], 0.50 [1.59] vs 0.49 [1.47]) per individual. In deterministic SPT sensitivity analyses at base-case sensitivity and specificity rates, screening could be cost-effective at a high disutility rate (the negative effect of a food allergic reaction) (76-148 days of life traded) for an at-home vs in-clinic reaction in combination with high baseline peanut allergy prevalence among infants at high risk for peanut allergy and not yet exposed to peanuts. If an equivalent rate and disutility of accidental and index anaphylaxis was assumed and the 8-mm SPT cutoff had 0.85 sensitivity and 0.98 specificity, screening was cost-effective at a peanut allergy prevalence of 36%.Conclusions and relevanceThe results of this study suggest that the current screening approach to early peanut introduction could be cost-effective at a particular health utility for an in-clinic reaction, SPT sensitivity and specificity, and high baseline peanut allergy prevalence among high-risk infants. However, such conditions are unlikely to be plausible to realistically achieve. Further research is needed to define the health state utility associated with reaction location.
| S-EPMC6991237 | biostudies-literature
Project description:BackgroundIdentification of risk factors for food allergy (FA) in infants is an active research area. An important reason is to identify optimal target infants for early introduction of specific food antigens. Although eczema has been used for this purpose, multivariable prediction scores have not been reported.ObjectiveThe aim of this research is to develop a multivariable prediction score for infants at high risk of FA.MethodsWe performed a cross-sectional analysis of a self-administered questionnaire for the parents of 18-month-old children at well-child visits between April 2016 and March 2017 (development dataset) and between April 2017 and March 2018 (validation dataset). We developed and validated the prediction score.ResultsThe questionnaire collection rate was 18,549 of 20,198 (92%) in the development dataset and 18,620 of 19,977 (93%) in the validation dataset. Risk factors for FA were being born in August-December, first child, eczema, atopic dermatitis in father and mother, and FA in mother and sibling(s). For identifying infants with FA, the developed multivariable prediction score showed higher discrimination ability (area under the curve [AUC] = 0.75) than focusing on eczema (AUC = 0.70) in the validation dataset. The score was also useful for identifying infants with a history of anaphylaxis (AUC = 0.73) than focusing on eczema (AUC = 0.67) in the validation dataset.ConclusionThe new prediction score enables more efficient identification of infants at high risk of FA, who may be the optimal target group for the early introduction of specific antigens.
| S-EPMC7870367 | biostudies-literature
Project description:The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of mouse whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for platelet aggregation, stronger and prolonged anemia and lung inflammation. The first two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria shows the validity of this approach to inform severity of the infection and provide insight into pathogenic mechanisms.
| S-EPMC5290525 | biostudies-literature
Project description:Cardiac surgery with cardiopulmonary bypass (CS/CPB) is associated with increased risk for postoperative complications causing substantial morbidity and mortality. To identify the molecular mechanisms underlying CS/CPB-induced pathophysiology we employed an integrative systems biology approach using the whole blood transcriptome as the sentinel organ.Total RNA was isolated and globin mRNA depleted from whole blood samples prospectively collected from 10 patients at time points prior (0), 2 and 24 hours following CS/CPB. Genome-wide transcriptional analysis revealed differential expression of 610 genes after CS/CPB (p<0.01). Among the 375 CS/CPB-upregulated genes, we found a gene-regulatory network consisting of 50 genes, reminiscent of activation of a coordinated genetic program triggered by CS/CPB. Intriguingly, the highly connected hub nodes of the identified network included key sensors of ischemia-reperfusion (HIF-1alpha and C/EBPbeta). Activation of this network initiated a concerted inflammatory response via upregulation of TLR-4/5, IL1R2/IL1RAP, IL6, IL18/IL18R1/IL18RAP, MMP9, HGF/HGFR, CalgranulinA/B, and coagulation factors F5/F12 among others. Differential regulation of 13 candidate genes including novel, not hitherto CS/CBP-associated genes, such as PTX3, PGK1 and Resistin, was confirmed using real-time quantitative RT-PCR. In support of the mRNA data, differential expression of MMP9, MIP1alpha and MIP1beta plasma proteins was further confirmed in 34 additional patients.Analysis of blood transcriptome uncovered critical signaling pathways governing the CS/CPB-induced pathophysiology. The molecular signaling underlying ischemia reperfusion and inflammatory response is highly intertwined and includes pro-inflammatory as well as cardioprotective elements. The herein identified candidate genes and pathways may provide promising prognostic biomarker and therapeutic targets.
| S-EPMC2965092 | biostudies-literature
Project description:BackgroundPeanut allergy is typically severe, lifelong, and prevalent.ObjectiveTo identify factors associated with peanut sensitization.MethodsWe evaluated 503 infants 3 to 15 months of age (mean, 9.4 months) with likely milk or egg allergy but no previous diagnosis of peanut allergy. A total of 308 had experienced an immediate allergic reaction to cow's milk and/or egg, and 204 had moderate to severe atopic dermatitis and a positive allergy test to milk and/or egg. A peanut IgE level ≥5 kU(A)/L was considered likely indicative of peanut allergy.ResultsA total of 140 (27.8%) infants had peanut IgE levels ≥5 kU(A)/L. Multivariate analysis including clinical, laboratory, and demographic variables showed frequent peanut consumption during pregnancy (odds ratio, 2.9; 95% CI, 1.7-4.9; P < .001), IgE levels to milk (P = .001) and egg (P < .001), male sex (P = .02), and nonwhite race (P = .02) to be the primary factors associated with peanut IgE ≥5 kUA/L. Frequency of peanut consumption during pregnancy and breast-feeding showed a dose-response association with peanut IgE ≥5 kU(A)/L, but only consumption during pregnancy was a significant predictor. Among 71 infants never breast-fed, frequent consumption of peanut during pregnancy was strongly associated with peanut IgE ≥5 kU(A)/L (odds ratio, 4.99, 95% CI, 1.69-14.74; P < .004).ConclusionIn this cohort of infants with likely milk or egg allergy, maternal ingestion of peanut during pregnancy was strongly associated with a high level of peanut sensitization.
| S-EPMC3018157 | biostudies-literature
Project description:Peanut allergens can trigger a potent and sometimes dangerous immune response in an increasing number of people. The molecular structures of these allergens form the basis for understanding this response. This review describes the currently known peanut allergen structures and discusses how modifications both enzymatic and non-enzymatic affect digestion, innate immune recognition, and IgE interactions. The allergen structures help explain cross-reactivity among allergens from different sources, which is useful in improving patient diagnostics. Surprisingly, it was recently noted that similar short peptide sequences among unrelated peanut allergens could also be a source of cross-reactivity. The molecular features of peanut allergens continue to inform predictions and provide new research directions in the study of allergic disease.
| S-EPMC4785306 | biostudies-literature
Project description:Peanut allergy (PA) is a common and serious food allergy and its prevalence has increased in the past decade. Although there is strong evidence of inheritance, the genetic causes of this disease are not well understood. Previously, a large-scale genome-wide association study described an association between human leukocyte antigen (HLA)-DQB1 and asthma; the aim of this study was to evaluate the association between HLA-DQB1 and PA. Genotypic and allelic profiles were established for 311 Caucasian members of a well-described Canadian group of children with PA and 226 Caucasian controls. Firth's logistic regression analyses showed associations between HLA-DQB1 alleles and PA for DQB1*02 (P=1.1 × 10(-8), odds ratio (OR)=0.09 (CI=0.03-0.23)) and DQB1*06:03P alleles (P=2.1 × 10(-2), OR=2.82 (CI=1.48-5.45)). This study of HLA in PA demonstrates specific association between two allelic groups of the HLA-DQB1 gene (DQB1*02 and DQB1*06:03P) and PA, highlighting its possible role in the development of this disease.
| S-EPMC3778350 | biostudies-literature