Filaggrin gene mutation associations with peanut allergy persist despite variations in peanut allergy diagnostic criteria or asthma status.
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ABSTRACT:
SUBMITTER: Asai Y
PROVIDER: S-EPMC3919206 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:BackgroundSpecific IgE to Ara h 2 is a diagnostic test for peanut allergy which may reduce the need for double-blind placebo-controlled food challenges (DBPCFC); however, guidance for using Ara h 2 in place of DBPCFCs has not been validated.ObjectiveTo prospectively evaluate 1) diagnostic accuracy of previously published Ara h 2 cut-off levels to diagnose peanut allergy in children and 2) costs.MethodsA consecutive series of 150 children age 3.5 to 18 years was evaluated in secondary and tertiary settings in the Netherlands. sIgE to Ara h 2 was the index test, and oral peanut ingestion was the reference test. Oral peanut ingestion was home or supervised introduction for Ara h 2 ≤ 0.1, DBPCFC for 0.1-5.0 and open food challenge for ≥5.0. Costs were calculated using financial healthcare data.ResultsA conclusive reference test was performed in 113 children (75%). Sixty-four children (57%) had peanut allergy, as confirmed by a DBPCFC (27/47) or an open challenge (37/50). Forty-nine children (43%) were considered peanut-tolerant after peanut introduction (19/19), a DBPCFC (20/47) or an open challenge (10/50). Area under the curve for Ara h 2 was 0.94 (95% CI 0.90-0.98). The diagnostic flow chart correctly classified 26/26 (100%; 84-100) of children with Ara h 2 ≤ 0.1 as peanut-tolerant and 34/35 (97%; 83-100) of children with Ara h 2 ≥ 5.0 as peanut-allergic. At a cut-off of ≤0.1 and ≥5.0, a sensitivity of respectively 100% (93-100) and 53% (38-67) was observed and a specificity of 53% (38-67) and 98% (87-100). Mean annual costs of the flow chart were estimated as €320-€636 per patient lower than following national allergy guidelines.ConclusionsIn this diagnostic accuracy study, which did not take into account pretest probability, we have validated previously published Ara h 2 cut-off levels which are associated with peanut tolerance and allergy.
| S-EPMC8456915 | biostudies-literature
Project description:BACKGROUND:The use of inflammatory biomarkers to delineate the type of lung inflammation present in asthmatic subjects is increasingly common. However, the effect of obesity on these markers is unknown. OBJECTIVES:We aimed to determine the effect of obesity on conventional markers of inflammation in asthmatic subjects. METHODS:We performed secondary analysis of data from 652 subjects previously enrolled in 2 Asthma Clinical Research Network trials. We performed linear correlations between biomarkers and logistic regression analysis to determine the predictive value of IgE levels, blood eosinophil counts, and fraction of exhaled nitric oxide values in relationship to sputum eosinophil counts (>2%), as well as to determine whether cut points existed that would maximize the sensitivity and specificity for predicting sputum eosinophilia in the 3 weight groups. RESULTS:Overall, statistically significant but relatively weak correlations were observed among all 4 markers of inflammation. Within obese subjects, the only significant correlation found was between IgE levels and blood eosinophil counts (r = 0.33, P < .001); furthermore, all other correlations between inflammatory markers were approximately 0, including correlations with sputum eosinophil counts. In addition, the predictive value of each biomarker alone or in combination was poor in obese subjects. In fact, in obese subjects none of the biomarkers of inflammation significantly predicted the presence of high sputum eosinophil counts. Obese asthmatic subjects have lower cut points for IgE levels (268 IU), fraction of exhaled nitric oxide values (14.5 ppb), and blood eosinophil counts (96 cells/?L) than all other groups. CONCLUSIONS:In obese asthmatic subjects conventional biomarkers of inflammation are poorly predictive of eosinophilic airway inflammation. As such, biomarkers currently used to delineate eosinophilic inflammation in asthmatic subjects should be approached with caution in these subjects.
| S-EPMC6076889 | biostudies-literature
Project description:BackgroundBronchial hyperresponsiveness (BHR) and asthma are frequently present in children with food allergy. We assessed BHR in children receiving oral immunotherapy (OIT) for persistent egg or peanut allergy and examined whether OIT affects asthma control.MethodsMethacholine challenge testing was performed in 89 children with persistent egg or peanut allergy diagnosed by double-blind, placebo-controlled food challenge and 80 control children without food allergy. Of the 89 food-allergic children, 50 started OIT for egg allergy and 39 for peanut allergy. Sensitization to aeroallergens was evaluated by skin prick testing. Forty of the 89 children with regular controller treatment for asthma underwent methacholine challenge testing and 34 measurement of exhaled nitric oxide (FeNO) at baseline and after 6-12 months of OIT.ResultsMethacholine challenge testing revealed significant BHR in 29/50 children (58%) with egg allergy, 15/39 children (38%) with peanut allergy, and 6/80 controls (7.5%). The mean cumulative dose of methacholine causing a 20% fall in FEV1 differed significantly between the egg and peanut-allergic versus the control children (1009 μg, 1104 μg, and 2068 μg, respectively, p < 0.001). Egg or peanut OIT did not affect lung function, the degree of BHR or FeNO levels in children with asthma and had no adverse effect on asthma control. Lung function or BHR did not associate with the OIT outcome.ConclusionBHR was significantly more frequent in children with persistent egg or peanut allergy than in children without food allergy. Oral immunotherapy did not increase BHR and was safe for children on regular asthma medication.
| S-EPMC9549178 | biostudies-literature
Project description:BackgroundMaternal diet during pregnancy may affect childhood allergy and asthma.ObjectiveWe sought to examine the associations between maternal intake of common childhood food allergens during early pregnancy and childhood allergy and asthma.MethodsWe studied 1277 mother-child pairs from a US prebirth cohort unselected for any disease. Using food frequency questionnaires administered during the first and second trimesters, we assessed maternal intake of common childhood food allergens during pregnancy. In mid-childhood (mean age, 7.9 years), we assessed food allergy, asthma, allergic rhinitis, and atopic dermatitis by questionnaire and serum-specific IgE levels. We examined the associations between maternal diet during pregnancy and childhood allergy and asthma. We also examined the cross-sectional associations between specific food allergies, asthma, and atopic conditions in mid-childhood.ResultsFood allergy was common (5.6%) in mid-childhood, as was sensitization to at least 1 food allergen (28.0%). Higher maternal peanut intake (each additional z score) during the first trimester was associated with 47% reduced odds of peanut allergic reaction (odds ratio [OR], 0.53; 95% CI, 0.30-0.94). Higher milk intake during the first trimester was associated with reduced asthma (OR, 0.83; 95% CI, 0.69-0.99) and allergic rhinitis (OR, 0.85; 95% CI, 0.74-0.97). Higher maternal wheat intake during the second trimester was associated with reduced atopic dermatitis (OR, 0.64; 95% CI, 0.46-0.90). Peanut, wheat, and soy allergy were each cross-sectionally associated with increased childhood asthma, atopic dermatitis, and allergic rhinitis (ORs, 3.6 to 8.1).ConclusionHigher maternal intake of peanut, milk, and wheat during early pregnancy was associated with reduced odds of mid-childhood allergy and asthma.
| S-EPMC4004710 | biostudies-literature
Project description:BACKGROUND: We previously estimated that the annual rate of accidental exposure to peanut in 1411 children with peanut allergy, followed for 2227 patient-years, was 11.9% (95% CI, 10.6, 13.5). This cohort has increased to 1941 children, contributing 4589 patient-years, and we determined the annual incidence of accidental exposure, described the severity, management, location, and identified associated factors. FINDINGS: Children with physician-confirmed peanut allergy were recruited from Canadian allergy clinics and allergy advocacy organizations from 2004 to May 2014. Parents completed questionnaires regarding accidental exposure to peanut over the preceding year. Five hundred and sixty-seven accidental exposures occurred in 429 children over 4589 patient-years, yielding an annual incidence rate of 12.4% (95% CI, 11.4, 13.4). Of 377 accidental exposures that were moderate or severe, only 109 (28.9%) sought medical attention and of these 109, only 40 (36.7%) received epinephrine. Of the 181 moderate/severe accidental exposures treated outside a health care facility, only 11.6% received epinephrine. Thirty-seven percent of accidental exposures occurred at home. In multivariate analyses, longer disease duration, recruitment through an allergy advocacy association, and having other food allergies decreased the likelihood of accidental exposures. Age ≥ 13 years at study entry and living with a single parent increased the risk. CONCLUSION: Despite increased awareness, accidental exposures continue to occur, mainly at home, and most are managed inappropriately by both health care professionals and caregivers. Consequently, more education is required on the importance of strict allergen avoidance and the need for prompt and correct management of anaphylaxis.
| S-EPMC4389801 | biostudies-other
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:Individual mice have a unique odor, or odortype, that facilitates individual recognition. Odortypes, like other phenotypes, can be influenced by genetic and environmental variation. The genetic influence derives in part from genes of the major histocompatibility complex (MHC). A major environmental influence is diet, which could obscure the genetic contribution to odortype. Because odortype stability is a prerequisite for individual recognition under normal behavioral conditions, we investigated whether MHC-determined urinary odortypes of inbred mice can be identified in the face of large diet-induced variation. Mice trained to discriminate urines from panels of mice that differed both in diet and MHC type found the diet odor more salient in generalization trials. Nevertheless, when mice were trained to discriminate mice with only MHC differences (but on the same diet), they recognized the MHC difference when tested with urines from mice on a different diet. This indicates that MHC odor profiles remain despite large dietary variation. Chemical analyses of urinary volatile organic compounds (VOCs) extracted by solid phase microextraction (SPME) and analyzed by gas chromatography/mass spectrometry (GC/MS) are consistent with this inference. Although diet influenced VOC variation more than MHC, with algorithmic training (supervised classification) MHC types could be accurately discriminated across different diets. Thus, although there are clear diet effects on urinary volatile profiles, they do not obscure MHC effects.
| S-EPMC2571990 | biostudies-literature
Project description:Peanut allergy (PA) has become a clinical and public health problem, which is mainly regulated by genetics, immune responses, and environmental factors. Diagnosis and treatment for PA have always remained huge challenges due to its multiple triggers. Studies have shown that long non-coding RNAs (lncRNAs) play a critical role in the development of allergic diseases. In the current study, we examined the plasma lncRNA expression profiles of peanut allergy Brown Norway rats and healthy controls and 496 differently expressed lncRNAs were identified, including 411 up-regulated genes and 85 down-regulated genes. We screened 8 lncRNAs based on the candidate principle and the candidates were verified in individual samples by quantitative real-time PCR. Then, the four lncRNA-based diagnostic model was established by least absolute shrinkage and selection operator (LASSO) and logistic regression, which was proved by area under the receiver operating characteristic curve (AUC). In summary, we assessed the correlation between lncRNA expression levels and the diagnosis of peanut allergy, which may perform a vital role in guiding the management of peanut allergy.
| S-EPMC9740276 | biostudies-literature
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