Timing of exposure to environmental adjuvants is critical to mitigate peanut allergy.
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ABSTRACT:
SUBMITTER: Smeekens JM
PROVIDER: S-EPMC7855661 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Timing of exposure to environmental adjuvants is critical to mitigate peanut allergy.
Smeekens Johanna M JM Immormino Robert M RM Kulis Michael D MD Moran Timothy P TP
The Journal of allergy and clinical immunology 20200924 1
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Project description:BackgroundA human study, Learning Early About Peanut Allergy (LEAP), showed that early introduction of peanut products decreases the prevalence of peanut allergy among children. However, the immunologic mechanisms mediating the protective effects of consuming peanut products are not well understood.ObjectiveThe objective was to develop a mouse model that simulates the LEAP study and investigate the underlying mechanisms for the study observations.MethodsAdult naive BALB/c mice were fed a commercial peanut butter product (Skippy) or buffer control and concomitantly exposed to peanut flour through the airway or skin to mimic environmental exposure. The animals were analyzed for anaphylactic reaction and by molecular and immunologic approaches.ResultsAfter exposure to peanut flour through the airway or skin, naive mice developed peanut allergy, as demonstrated by acute and systemic anaphylaxis in response to challenge with peanut extract. Ingestion of Skippy, however, nearly abolished the increase in peanut-specific IgE and IgG and protected animals from developing anaphylaxis. Skippy-fed mice showed reduced numbers of T follicular helper (Tfh) cells and germinal center B cells in their draining lymph nodes, and single-cell RNA sequencing revealed a CD4+ T-cell population expressing cytotoxic T lymphocyte-associated protein 4 (CTLA-4) in these animals. Critically, blocking CTLA-4 with antibody increased levels of peanut-specific antibodies and reversed the protective effects of Skippy.ConclusionIngestion of a peanut product protects mice from peanut allergy induced by environmental exposure to peanuts, and the CTLA-4 pathway, which regulates Tfh cell responses, likely plays a pivotal role in this protection.
| S-EPMC9378358 | 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:Allergic diseases are reaching epidemic proportions in developed countries. In particular, food allergy is increasing in prevalence and severity, thus becoming an important socioeconomic burden. Numerous cell types and cell populations, which form an intricate and balanced network, are involved in an immune response. This balance is occasionally disturbed, leading to the onset of different diseases, such as allergic diseases. Antihistamines and corticosteroids provide some degree of relief from the symptoms of allergic conditions. However, the only treatment that can revert the disease is immunotherapy. Nevertheless, specific immunotherapy has at least 2 major drawbacks: it is time-consuming, and it can produce local and even systemic allergic side effects. Immunotherapy's potential goes beyond our current knowledge of the immune response; nevertheless, we can still design strategies to reach a safer immune modulation for treating allergies. This review deals with the use of adjuvants to reduce the undesirable side effects associated with specific allergen immunotherapy. For example, nanoparticles used as immunoadjuvants are offering promising results in preclinical assays.
| S-EPMC5647973 | biostudies-literature
Project description:BackgroundThe impact of maternal ingestion of peanut during pregnancy and lactation on an offspring's risk for peanut allergy is under debate.ObjectiveTo investigate the influence of maternal dietary peanut exposure and breast milk on an offspring's allergy risk.MethodsPreconceptionally peanut-exposed C3H/HeJ females were either fed or not fed peanut during pregnancy and lactation. The offsprings' responses to peanut sensitization or oral tolerance induction by feeding antigen prior to immunization were assessed. We also assessed the impact of immune murine milk on tolerance induction pre- or post-weaning. For antigen uptake studies, mice were gavaged with fluorescent peanut in the presence or absence of immune murine milk; Peyer's patches were harvested for immunostaining.ResultsPreconceptional peanut exposure resulted in the production of varying levels of maternal antibodies in serum (and breast milk), which were transferred to the offspring. Despite this, maternal peanut exposure either preconceptionally or during pregnancy and lactation, when compared to no maternal exposure, had no impact on peanut allergy. When offspring were fed peanut directly, dose-dependent tolerance induction, unaltered by maternal feeding of peanut, was seen. Although peanut uptake into the gut-associated lymphoid tissues was enhanced by immune milk as compared to naïve milk, tolerance induction was not affected by the co-administration of immune milk either pre- or post-weaning.ConclusionMaternal peanut exposure during pregnancy and lactation has no impact on the development of peanut allergy in the offspring. Tolerance to peanut can be induced early, even pre-weaning, by giving moderate amounts of peanut directly to the infant, and this is neither enhanced nor impaired by concurrent exposure to immune milk.
| S-EPMC4675539 | 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:BackgroundIn regions with a high prevalence of peanut allergy (PA), there is a consensus that the introduction of peanuts in early infancy is preventive against the development of PA. However, few studies have investigated whether the introduction of peanuts to infants is associated with PA in regions with a low prevalence of PA, including Japan.MethodsWe used data from 74,240 mother-child pairs who participated in the Japan Environment and Children's Study, a prospective birth cohort recruited between January 2011 and March 2014. A logistic regression model was used to analyze the association between infantile peanut introduction and PA at the age of 4 years with non-infantile peanut introduction as the reference group, adjusted for potential confounders.ResultsThe percentage of infantile peanut introduction was 4.9% (n=3294) and 286 (0.4%) participants had allergic symptoms to peanuts at 4 years of age. Of all participants, 129 (0.2%) had PA at 4 years of age, which was defined as allergic symptoms and sensitization to peanuts. Those with infantile peanut introduction had a lower prevalence of PA than those without infantile peanut introduction, although this did not reach statistical significance (adjusted odds ratio: 0.53, 95% confidence interval, 0.17-1.68). Sensitivity analysis using IgE-mediated symptoms caused by peanuts as the outcome showed a similar result in relation to infantile peanut introduction.ConclusionsIn countries with a low prevalence of PA, the effect of infantile peanut introduction on PA prevention was unclear.
| S-EPMC11167260 | 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: Not available
| S-EPMC3919206 | biostudies-literature
Project description:Background: 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. Method and Results: 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). Conclusions: 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 Learning Early About Peanut Allergy (LEAP) study team developed a protocol-specific algorithm using dietary history, peanut-specific IgE, and skin prick test (SPT) to determine peanut allergy status if the oral food challenge (OFC) could not be administered or did not provide a determinant result.ObjectiveTo investigate how well the algorithm determined allergy status in LEAP; to develop a new prediction model to determine peanut allergy status when OFC results are not available in LEAP Trio, a follow-up study of LEAP participants and their families; and to compare the new prediction model with the algorithm.MethodsThe algorithm was developed for the LEAP protocol before the analysis of the primary outcome. Subsequently, a prediction model was developed using logistic regression.ResultsUsing the protocol-specified algorithm, 73% (453/617) of allergy determinations matched the OFC, 0.6% (4/617) were mismatched, and 26% (160/617) participants were nonevaluable. The prediction model included SPT, peanut-specific IgE, Ara h 1, Ara h 2, and Ara h 3. The model inaccurately predicted 1 of 266 participants as allergic who were not allergic by OFC and 8 of 57 participants as not allergic who were allergic by OFC. The overall error rate was 9 of 323 (2.8%) with an area under the curve of 0.99. The prediction model additionally performed well in an external validation cohort.ConclusionThe prediction model performed with high sensitivity and accuracy, eliminated the problem of nonevaluable outcomes, and can be used to estimate peanut allergy status in the LEAP Trio study when OFC is not available.
| S-EPMC11837399 | biostudies-literature