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1.
Pediatr Allergy Immunol ; 35(6): e14140, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38822743

RESUMO

Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta-analysis on BAT and MAT, assessing their specificity and sensitivity in diagnosing peanut allergy. Six databases were searched for studies on patients suspected of having peanut allergy. Studies using BAT or MAT to peanut extract and/or component as diagnostic tools with results given in percentage of CD63 activation were included in this meta-analysis. Study quality was evaluated with the QUADAS-2 tool. On the 11 studies identified, eight focused exclusively on children, while three included a mixed population of adults and children. Only one study provided data on MAT, precluding us from conducting a statistical analysis. The diagnostic accuracy of BAT was higher when stimulated with peanut extract rather than Ara h 2 with a pooled specificity of 96% (95% CI: 0.89-0.98) and sensitivity of 0.86 (95% CI: 0.74-0.93). The sensitivity and specificity of BATs in discriminating between allergic and sensitized patients were studied as well, with pooled analysis revealing a sensitivity of 0.86 (95% CI: 0.74; 0.93) and a specificity of 0.97 (95% CI: 0.94, 0.98). BATs, when stimulated with peanut extracts, exhibit a satisfactory sensitivity and specificity for the diagnosis of peanut allergy and can help to discriminate between allergic individuals and those only sensitized to peanuts. More investigations on the potential for MATs diagnostic methods are warranted.


Assuntos
Hipersensibilidade a Amendoim , Sensibilidade e Especificidade , Hipersensibilidade a Amendoim/diagnóstico , Hipersensibilidade a Amendoim/imunologia , Humanos , Basófilos/imunologia , Arachis/imunologia , Criança , Mastócitos/imunologia , Teste de Degranulação de Basófilos/métodos , Alérgenos/imunologia , Adulto
2.
NEJM Evid ; 3(6): EVIDoa2300311, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38804779

RESUMO

BACKGROUND: A randomized trial demonstrated consumption of peanut from infancy to age 5 years prevented the development of peanut allergy. An extension of that trial demonstrated the effect persisted after 1 year of peanut avoidance. This follow-up trial examined the durability of peanut tolerance at age 144 months after years of ad libitum peanut consumption. METHODS: Participants from a randomized peanut consumption trial were assessed for peanut allergy following an extended period of eating or avoiding peanuts as desired. The primary end point was the rate of peanut allergy at age 144 months. RESULTS: We enrolled 508 of the original 640 participants (79.4%); 497 had complete primary end point data. At age 144 months, peanut allergy remained significantly more prevalent in participants in the original peanut avoidance group than in the original peanut consumption group (15.4% [38 of 246 participants] vs. 4.4% [11 of 251 participants]; P<0.001). Participants in both groups reported avoiding peanuts for prolonged periods of time between 72 and 144 months. Participants at 144 months in the peanut consumption group had levels of Ara h2-specific immunoglobulin E (a peanut allergen associated with anaphylaxis) of 0.03 ± 3.42 kU/l and levels of peanut-specific immunoglobulin G4 of 535.5 ± 4.98 µg/l, whereas participants in the peanut avoidance group had levels of Ara h2-specific immunoglobulin E of 0.06 ± 11.21 kU/l and levels of peanut-specific immunoglobulin G4 of 209.3 ± 3.84 µg/l. Adverse events were uncommon, and the majority were related to the food challenge. CONCLUSIONS: Peanut consumption, starting in infancy and continuing to age 5 years, provided lasting tolerance to peanut into adolescence irrespective of subsequent peanut consumption, demonstrating that long-term prevention and tolerance can be achieved in food allergy. (Funded by the National Institute of Allergy and Infectious Diseases and others; ITN070AD, ClinicalTrials.gov number, NCT03546413.).


Assuntos
Arachis , Hipersensibilidade a Amendoim , Humanos , Hipersensibilidade a Amendoim/prevenção & controle , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/epidemiologia , Seguimentos , Arachis/imunologia , Feminino , Masculino , Pré-Escolar , Lactente , Adolescente , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Criança , Tolerância Imunológica
3.
Pediatr Allergy Immunol ; 35(5): e14146, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38783409

RESUMO

BACKGROUND: Oral immunotherapy (OIT) is an increasingly acceptable therapeutic option for peanut-allergic (PA) children, despite significant side effects. Major peanut allergenic proteins are heat-resistant and are not rendered hypoallergenic after baking or cooking. Lyophilized peanut protein-MH (LPP-MH) is a novel composition from developing peanuts, enabling cooking-induced reduction in allergenicity. We aimed to explore the safety and efficacy of OIT, with extensively heated and baked (EHEB) LPP-MH in PA children. METHODS: In a single-arm, single-center, pilot study, PA children with a single highest tolerated dose of <100 mg peanut protein were placed on a 40-week OIT protocol with 300 mg daily of heat-treated LPP-MH. A repeat open peanut food challenge was performed after 40 weeks of treatment and at a 6-12 months of follow-up visit. RESULTS: Thirty-three children with PA were enrolled, with a mean cumulative tolerated dose (MCTD) of 71.2 mg PP (95% CI 45-100 mg). After 40 weeks, 32/33 patients were able to consume more than 300 mg of natural PP, with MCTD of 1709 mg (CI 365-3675 mg). There were no severe allergic reactions requiring epinephrine, during any of the observed LPP-MH challenges or any treatment related doses at home. After 6-12 months on daily maintenance, the MCTD was 8821 mg (95% CI 1930-13,500 mg). This enabled most children age-appropriate dietary inclusion of peanuts. CONCLUSION: An OIT protocol with heat-treated LPP-MH, a novel composition from developing peanuts, seems a potentially safe and efficacious OIT modality for PA children, enabling the introduction of dietary levels of peanut proteins in highly allergic PA children. Validation in randomized controlled studies is mandated.


Assuntos
Alérgenos , Arachis , Culinária , Dessensibilização Imunológica , Hipersensibilidade a Amendoim , Humanos , Hipersensibilidade a Amendoim/terapia , Hipersensibilidade a Amendoim/imunologia , Arachis/imunologia , Dessensibilização Imunológica/métodos , Masculino , Criança , Feminino , Administração Oral , Projetos Piloto , Alérgenos/imunologia , Alérgenos/administração & dosagem , Pré-Escolar , Temperatura Alta , Resultado do Tratamento , Adolescente , Proteínas de Plantas/imunologia , Proteínas de Plantas/administração & dosagem
4.
J Agric Food Chem ; 72(19): 11259-11267, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38691423

RESUMO

Peanut allergen monitoring is currently an effective strategy to avoid allergic diseases, while food matrix interference is a critical challenge during detection. Here, we developed an antifouling surface plasmon resonance sensor (SPR) with stratified zwitterionic peptides, which provides both excellent antifouling and sensing properties. The antifouling performance was measured by the SPR, which showed that stratified peptide coatings showed much better protein resistance, reaching ultralow adsorption levels (<5 ng/cm2). Atomic force microscopy was used to further analyze the antifouling mechanism from a mechanical perspective, which demonstrated lower adsorption forces on hybrid peptide coatings, confirming the better antifouling performance of stratified surfaces. Moreover, the recognition of peanut allergens in biscuits was performed using an SPR with high efficiency and appropriate recovery results (98.2-112%), which verified the feasibility of this assay. Therefore, the fabrication of antifouling sensors with stratified zwitterionic peptides provides an efficient strategy for food safety inspection.


Assuntos
Alérgenos , Arachis , Peptídeos , Ressonância de Plasmônio de Superfície , Ressonância de Plasmônio de Superfície/métodos , Arachis/química , Arachis/imunologia , Peptídeos/química , Peptídeos/imunologia , Alérgenos/análise , Alérgenos/imunologia , Alérgenos/química , Incrustação Biológica/prevenção & controle , Contaminação de Alimentos/análise , Proteínas de Plantas/imunologia , Proteínas de Plantas/química , Proteínas de Plantas/análise , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Adsorção
5.
Pediatr Allergy Immunol ; 35(4): e14127, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38646959

RESUMO

Peanut allergy affects about 1%-3% of the pediatric population in the world, with an important increase in the last decades. Nowadays, international guidelines recommend the early introduction of peanuts in the infant diet, with poor information about the quantity and the frequency of the intake. Allergen immunotherapy may represent the only therapeutic strategy able to modify the natural history of peanut allergy. In particular, oral immunotherapy showed the most promising results in terms of efficacy, but with significant rates of adverse reactions, mostly gastrointestinal. In 2020, the Food and Drug Administration and the European Medicines Agency approved Palforzia®, an oral drug for patients aged 4-17 years. Several studies are ongoing to improve the tolerability of oral immunotherapy and standardize the desensitization protocols. Sublingual immunotherapy permits to offer much lower doses than oral immunotherapy, but fewer adverse events are shown. Subcutaneous immunotherapy is associated with the greatest systemic adverse effects. Epicutaneous immunotherapy, for which Viaskin® patch was approved, has the highest safety profile. Innovative studies are evaluating the use of biological drugs, such as omalizumab or dupilumab, and probiotics, such as Lactobacillus rhamnosus, in monotherapy or associated with oral immunotherapy. Therapy for peanut allergy is constantly evolving, and new perspectives are ongoing to develop.


Assuntos
Alérgenos , Dessensibilização Imunológica , Hipersensibilidade a Amendoim , Humanos , Hipersensibilidade a Amendoim/terapia , Hipersensibilidade a Amendoim/imunologia , Dessensibilização Imunológica/métodos , Criança , Pré-Escolar , Adolescente , Alérgenos/imunologia , Alérgenos/administração & dosagem , Administração Oral , Arachis/imunologia , Probióticos/uso terapêutico , Probióticos/administração & dosagem
6.
Curr Allergy Asthma Rep ; 24(6): 303-315, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38639896

RESUMO

PURPOSE OF REVIEW: Based on shared decision-making (SDM) principles, a decision aid was previously developed to help patients, their caregivers, and physicians decide which peanut allergy management approach best suits them. This study refined the decision aid's content to better reflect patients' and caregivers' lived experience. RECENT FINDINGS: Current standard of care for peanut allergy is avoidance, although peanut oral immunotherapy has been approved by the Food and Drug Administration for use in patients 4-17 years old. An advisory board of allergy therapy experts (n = 3) and patient advocates (n = 3) informed modifications to the decision aid. The revised tool underwent cognitive debriefing interviews (CDIs) among adolescents (12-17 years old) with peanut allergy and caregivers of patients 4-17 years old with peanut allergy to evaluate its relevance, understandability, and usefulness. The 20 CDI participants understood the information presented in the SDM tool and reported it was important and relevant. Some revisions were made based on participant feedback. Results support content validity of the Peanut Allergy Treatment SDM Tool.


Assuntos
Tomada de Decisão Compartilhada , Hipersensibilidade a Amendoim , Humanos , Hipersensibilidade a Amendoim/terapia , Hipersensibilidade a Amendoim/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Masculino , Técnicas de Apoio para a Decisão , Cuidadores/psicologia , Dessensibilização Imunológica/métodos , Arachis/imunologia
7.
J Allergy Clin Immunol Pract ; 12(5): 1297-1305, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38428524

RESUMO

BACKGROUND: The prevalence of peanut allergy is about 2% and mostly lifelong. Studies of oral immunotherapy (OIT) with peanut (the daily oral intake of an initially low and then increasing dose of peanut) often show problematic side effects, but there are indications of better safety and effect in younger children compared with older children and adults. OBJECTIVE: To determine the safety and effectiveness of peanut OIT with a slow up-dosing strategy and low maintenance dose in children aged 1 to 3 years who were allergic to peanut, through a 1-year interim analysis. METHOD: In a randomized controlled trial (2:1 ratio), 75 children, median age 31 months (interquartile range [IQR], 23-40 months) were assigned to receive peanut OIT (n = 50) or peanut avoidance (n = 25). RESULTS: In the OIT and avoidance groups, 43 of 50 and 20 of 25 children, respectively, performed the 1-year open oral peanut challenge. A cumulative dose of 750 mg peanut protein after 1 year was tolerated by 72% (36 of 50 children) in the OIT group compared with 4% (1 of 25) in the avoidance group (P < .001). Median tolerated cumulative dose was 2,750 mg (IQR, 275-5,000 mg) peanut protein in the OIT group compared with 2.8 mg (IQR, 0.3-27.8 mg) in the avoidance group (P < .001). Of the doses administered at home during the first year of OIT, 1.4% resulted in adverse events and 79% were mild, and three doses of epinephrine were given at home to two individuals. CONCLUSION: In children aged 1 to 3 years, peanut OIT with the combination of slow up-dosing and low maintenance dose seems safe and effective after 1 year.


Assuntos
Alérgenos , Arachis , Dessensibilização Imunológica , Hipersensibilidade a Amendoim , Humanos , Hipersensibilidade a Amendoim/terapia , Hipersensibilidade a Amendoim/imunologia , Pré-Escolar , Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/efeitos adversos , Masculino , Feminino , Administração Oral , Lactente , Arachis/imunologia , Alérgenos/imunologia , Alérgenos/administração & dosagem , Resultado do Tratamento
8.
Expert Rev Clin Immunol ; 20(6): 623-633, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38323337

RESUMO

INTRODUCTION: DBV712 250 µg (also referred to as Viaskin Peanut or peanut patch; Viaskin is a trademark of DBV Technologies) is an innovative approach to epicutaneous immunotherapy (EPIT). The patch-based technology system facilitates peanut protein (allergen) absorption into the intact non-vascularized epidermis to promote desensitization to peanut while limiting systemic allergen exposure. AREAS COVERED: Efficacy and safety in children have been evaluated in four completed phase 3 studies. Overall, the results from these studies have demonstrated the peanut patch to be superior in desensitization compared with placebo and safe for daily use over multiple years. EXPERT OPINION: These findings, as well as supportive evidence from phase 2 studies, confirm the potential for an effective treatment of peanut allergy in children. The purpose of this review is to summarize the safety and efficacy of the peanut patch in the treatment of peanut allergy.


Assuntos
Alérgenos , Arachis , Dessensibilização Imunológica , Hipersensibilidade a Amendoim , Hipersensibilidade a Amendoim/terapia , Hipersensibilidade a Amendoim/imunologia , Humanos , Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/efeitos adversos , Arachis/imunologia , Alérgenos/imunologia , Alérgenos/administração & dosagem , Criança , Administração Cutânea , Resultado do Tratamento
9.
Lancet Child Adolesc Health ; 6(3): 171-184, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35123664

RESUMO

BACKGROUND: Oral immunotherapy is effective at inducing desensitisation to allergens and induces sustained unresponsiveness (ie, clinical remission) in a subset of patients, but causes frequent reactions. We aimed to investigate whether addition of a probiotic adjuvant improved the efficacy or safety of peanut oral immunotherapy. METHODS: PPOIT-003, a multicentre, randomised, phase 2b trial, was conducted in three tertiary hospitals in Australia (Adelaide [SA], Melbourne [VIC], and Perth [WA]) in children aged 1-10 years, weighing more than 7 kg, with peanut allergy confirmed by a double-blind placebo-controlled food challenge (cumulative 4950 mg dose of peanut protein) and positive peanut skin prick test (≥3 mm) or peanut-specific IgE (≥0·35 kU/L). Children were randomly assigned (2:2:1) to receive probiotic and peanut oral immunotherapy (PPOIT), placebo probiotic and peanut oral immunotherapy (OIT), or placebo probiotic and placebo OIT (placebo) for 18 months, and were followed up until 12 months after completion of treatment. Oral immunotherapy consisted of increasing doses of peanut protein (commercially available food-grade 12% defatted peanut flour [50% peanut protein]) until a 2000 mg daily maintenance dose was reached. The probiotic adjuvant was a daily dose of 2 × 1010 colony-forming units of the probiotic Lactobacillus rhamnosus ATCC 53103. Placebo immunotherapy comprised maltodextrin, brown food colouring, and peanut essence, and placebo probiotic was maltodextrin. Dual primary outcomes were 8-week sustained unresponsiveness, defined as no reaction to a cumulative dose of 4950 mg peanut protein at treatment completion and 8 weeks after treatment completion, in the PPOIT versus placebo groups and the PPOIT versus OIT groups, analysed by intention to treat. Safety endpoints were adverse events during the treatment phase, and peanut ingestion and reactions in the 12-month post-treatment period. This study is registered with the Australian New Zealand Clinical Trials Registry, 12616000322437. FINDINGS: Between July 4, 2016, and Sept 21, 2020, 201 participants were enrolled and included in the intention-to-treat analysis. 36 (46%) of 79 children in the PPOIT group and 42 (51%) of 83 children in the OIT group achieved sustained unresponsiveness compared with two (5%) of 39 children in the placebo group (risk difference 40·44% [95% CI 27·46 to 53·42] for PPOIT vs placebo, p<0·0001), with no difference between PPOIT and OIT (-5·03% [-20·40 to 10·34], p=0·52). Treatment-related adverse events were reported in 72 (91%) of 79 children in the PPOIT group, 73 (88%) of 83 children in the OIT group, and 28 (72%) of 39 children in the placebo group. Exposure-adjusted incidence of adverse events was 10·58 in the PPOIT group, 11·36 in the OIT, and 2·09 in the placebo group (ratio 0·92 [95% CI 0·85 to 0·99] for PPOIT vs OIT, p=0·042; 4·98 [4·11-6·03] for PPOIT vs placebo, p<0·0001; 5·42 [4·48-6·56] for OIT vs placebo, p<0·0001), with differences seen primarily in gastrointestinal symptoms and in children aged 1-5 years. During the 12-month post-treatment period, 60 (85%) of 71 participants in the PPOIT group, 60 (86%) of 70 participants in the OIT group, and six (18%) of 34 participants in the placebo group were eating peanut; rescue epinephrine use was infrequent (two [3%] of 71 in the PPOIT group, four [6%] of 70 in the OIT group, and none in the placebo group). INTERPRETATION: Both PPOIT and OIT were effective at inducing sustained unresponsiveness. Addition of a probiotic did not improve efficacy of OIT, but might offer a safety benefit compared with OIT alone, particularly in preschool children. FUNDING: National Health and Medical Research Council Australia and Prota Therapeutics.


Assuntos
Alérgenos/administração & dosagem , Arachis/imunologia , Dessensibilização Imunológica/métodos , Fatores Imunológicos/administração & dosagem , Lacticaseibacillus rhamnosus/imunologia , Hipersensibilidade a Amendoim/terapia , Probióticos/administração & dosagem , Administração Oral , Austrália , Criança , Pré-Escolar , Proteínas Alimentares/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Qualidade de Vida , Centros de Atenção Terciária , Resultado do Tratamento
10.
Int J Mol Sci ; 23(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35055026

RESUMO

The cultivated peanut (Arachis hypogaea L.) is a legume consumed worldwide in the form of oil, nuts, peanut butter, and candy. Improving peanut production and nutrition will require new technologies to enable novel trait development. Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) is a powerful and versatile genome-editing tool for introducing genetic changes for studying gene expression and improving crops, including peanuts. An efficient in vivo transient CRISPR-Cas9- editing system using protoplasts as a testbed could be a versatile platform to optimize this technology. In this study, multiplex CRISPR-Cas9 genome editing was performed in peanut protoplasts to disrupt a major allergen gene with the help of an endogenous tRNA-processing system. In this process, we successfully optimized protoplast isolation and transformation with green fluorescent protein (GFP) plasmid, designed two sgRNAs for an allergen gene, Ara h 2, and tested their efficiency by in vitro digestion with Cas9. Finally, through deep-sequencing analysis, several edits were identified in our target gene after PEG-mediated transformation in protoplasts with a Cas9 and sgRNA-containing vector. These findings demonstrated that a polyethylene glycol (PEG)-mediated protoplast transformation system can serve as a rapid and effective tool for transient expression assays and sgRNA validation in peanut.


Assuntos
Albuminas 2S de Plantas/genética , Antígenos de Plantas/genética , Arachis/genética , Edição de Genes , Protoplastos , Arachis/imunologia , Sistemas CRISPR-Cas , Marcação de Genes , Vetores Genéticos/genética , Projetos Piloto , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Regiões Promotoras Genéticas , RNA Guia de Cinetoplastídeos , Plântula , Temperatura , Transfecção/métodos
12.
J Clin Invest ; 132(1)2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34981779

RESUMO

The rising incidence of food allergy in children underscores the importance of environmental exposures; however, genetic factors play a major role. How the environment and genetics interact to cause food allergy remains unclear. The landmark Learning Early About Peanut Allergy (LEAP) clinical trial established that early peanut introduction protects high-risk infants, consistent with the tolerizing effects of gut exposure. In this issue of the JCI, Kanchan et al. leveraged the LEAP trial data to examine molecular genetic mechanisms of early sensitization. A previously identified HLA risk allele for peanut allergy (DQA1*01:02) was associated with peanut-specific IgG4 levels in consumers. Notably, IgG4 antibodies likely provide protection by reducing the binding of allergen to IgE. The association of the same allele with peanut allergy in avoiders while potentially conferring protection in consumers reinforces the need to integrate genetic information toward a personalized therapeutic strategy for the best outcome in addressing food allergies.


Assuntos
Arachis , Hipersensibilidade a Amendoim , Alelos , Alérgenos , Arachis/genética , Arachis/imunologia , Criança , Cadeias alfa de HLA-DQ , Humanos , Lactente , Hipersensibilidade a Amendoim/genética
13.
Lancet ; 399(10322): 359-371, 2022 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-35065784

RESUMO

BACKGROUND: For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population. METHODS: We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160. FINDINGS: Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy. INTERPRETATION: In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy. FUNDING: National Institute of Allergy and Infectious Disease, Immune Tolerance Network.


Assuntos
Alérgenos/administração & dosagem , Arachis/imunologia , Dessensibilização Imunológica , Hipersensibilidade a Amendoim/prevenção & controle , Administração Oral , Alérgenos/imunologia , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Tolerância Imunológica , Masculino , Hipersensibilidade a Amendoim/imunologia , Resultado do Tratamento
14.
J Allergy Clin Immunol ; 149(1): 262-274, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34051223

RESUMO

BACKGROUND: The etiology of food allergy is poorly understood; mouse models are powerful systems to discover immunologic pathways driving allergic disease. C3H/HeJ mice are a widely used model for the study of peanut allergy because, unlike C57BL/6 or BALB/c mice, they are highly susceptible to oral anaphylaxis. However, the immunologic mechanism of this strain's susceptibility is not known. OBJECTIVE: We aimed to determine the mechanism underlying the unique susceptibility to anaphylaxis in C3H/HeJ mice. We tested the role of deleterious Toll-like receptor 4 (Tlr4) or dedicator of cytokinesis 8 (Dock8) mutations in this strain because both genes have been associated with food allergy. METHODS: We generated C3H/HeJ mice with corrected Dock8 or Tlr4 alleles and sensitized and challenged them with peanut. We then characterized the antibody response to sensitization, anaphylaxis response to both oral and systemic peanut challenge, gut microbiome, and biomarkers of gut permeability. RESULTS: In contrast to C3H/HeJ mice, C57BL/6 mice were resistant to anaphylaxis after oral peanut challenge; however, both strains undergo anaphylaxis with intraperitoneal challenge. Restoring Tlr4 or Dock8 function in C3H/HeJ mice did not protect from anaphylaxis. Instead, we discovered enhanced gut permeability resulting in ingested allergens in the bloodstream in C3H/HeJ mice compared to C57BL/6 mice, which correlated with an increased number of goblet cells in the small intestine. CONCLUSIONS: Our work highlights the potential importance of gut permeability in driving anaphylaxis to ingested food allergens; it also indicates that genetic loci outside of Tlr4 and Dock8 are responsible for the oral anaphylactic susceptibility of C3H/HeJ mice.


Assuntos
Mucosa Intestinal/metabolismo , Anafilaxia Cutânea Passiva , Hipersensibilidade a Amendoim/metabolismo , Administração Oral , Animais , Arachis/imunologia , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal , Predisposição Genética para Doença , Fatores de Troca do Nucleotídeo Guanina/genética , Masculino , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Mutação , Anafilaxia Cutânea Passiva/genética , Hipersensibilidade a Amendoim/genética , Hipersensibilidade a Amendoim/microbiologia , Permeabilidade , Especificidade da Espécie , Receptor 4 Toll-Like/genética
15.
Arch Pediatr ; 29(2): 81-89, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34955309

RESUMO

During the past years, there has been an alarming increase in cases of food allergy and anaphylaxis in ever-younger children. Often, these children have multiple food allergies and food sensitizations, involving allergens with high anaphylactic potential, such as peanuts and nuts, which have a major influence on their quality of life and future. After reviewing the current epidemiological data, we discuss the main causes of the increase in food allergies. We analyze data from studies on the skin barrier and its fundamental role in the development of sensitization and food allergies, data on the tolerogenic digestive tract applied in particular to hen eggs and peanuts, as well as data on the prevention of allergy to cow milk proteins. In light of these studies, we propose a practical guide of recommendations focused on infants and the introduction of cow milk, the management of eczema, and early and broad dietary diversification including high-risk food allergens, such as peanut and nuts while taking into account the food consumption habits of the family.


Assuntos
Alérgenos/imunologia , Arachis/imunologia , Hipersensibilidade Alimentar/prevenção & controle , Alergistas , Anafilaxia/prevenção & controle , Animais , Bovinos , Galinhas , Criança , Dermatite Atópica/prevenção & controle , Feminino , Hipersensibilidade Alimentar/epidemiologia , Humanos , Lactente , Prevenção Primária/tendências , Qualidade de Vida
16.
Nutrients ; 13(11)2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34836333

RESUMO

BACKGROUND: Nut allergies are an increasingly frequent health issue in the pediatric population. Tree nuts (TN) and peanuts are the second cause of food anaphylaxis in Italy. Unfortunately, knowledge of the clinical characteristics of a TN allergy in Italian children is limited. Our study aimed to identify the clinical and allergological characteristics of Italian children with a nut allergy (TN and peanut). METHODS: A retrospective observational analysis was performed on the clinical charts of children with a history of nut reaction referred to the allergy unit of the hospital from 2015 to 2019. The studied population was represented by children with a confirmed nut allergy based on positive prick by prick and/or serum-specific IgE to nut plus a positive nut oral food challenge. Demographic, clinical, and allergological features were studied and compared among different nuts. RESULTS: In total, 318 clinical charts were reviewed. Nut allergy was confirmed in 113 patients. Most patients (85/113, 75%) had a familial history of allergy and/or a concomitant allergic disorder (77/113, 68%). Hazelnut and walnut were the more common culprit nuts observed in allergic children. Anaphylaxis was the first clinical manifestation of nut allergy in a high percentage of children (54/113, 48%). The mean age of the first nut reaction was statistically higher with pine nuts. Over 75% of children reported a single nut reaction. During the OFCs, the signs and symptoms involved mainly the gastrointestinal system (82/113, 73%) and resolved spontaneously in most cases. Severe reactions were not frequent (22/113, 19%). CONCLUSION: To our knowledge, this is the first Italian study that provided a comprehensive characterization of children with a nut allergy. These results are important for clinicians treating children with a nut allergy.


Assuntos
Alérgenos/imunologia , Arachis/imunologia , Hipersensibilidade a Nozes e Amendoim/epidemiologia , Hipersensibilidade a Nozes e Amendoim/imunologia , Nozes/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Itália/epidemiologia , Masculino , Hipersensibilidade a Nozes e Amendoim/sangue , Estudos Retrospectivos
17.
Cell Rep Med ; 2(10): 100410, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34755130

RESUMO

Peanut allergy can result in life-threatening reactions and is a major public health concern. Oral immunotherapy (OIT) induces desensitization to food allergens through administration of increasing amounts of allergen. To dissect peanut-specific immunoglobulin E (IgE) and IgG responses in subjects undergoing OIT, we have developed AllerScan, a method that leverages phage-display and next-generation sequencing to identify the epitope targets of peanut-specific antibodies. We observe a striking diversification and boosting of the peanut-specific IgG repertoire after OIT and a reduction in pre-existing IgE levels against individual epitopes. High-resolution epitope mapping reveals shared recognition of public epitopes in Ara h 1, 2, 3, and 7. In individual subjects, OIT-induced IgG specificities overlap extensively with IgE and exhibit strikingly similar antibody footprints, suggesting related clonal lineages or convergent evolution of peanut-specific IgE and IgG B cells. Individual differences in epitope recognition identified via AllerScan could inform safer and more effective personalized immunotherapy.


Assuntos
Dessensibilização Imunológica/métodos , Mapeamento de Epitopos/métodos , Epitopos/química , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Omalizumab/uso terapêutico , Hipersensibilidade a Amendoim/terapia , Albuminas 2S de Plantas/administração & dosagem , Albuminas 2S de Plantas/química , Antígenos de Plantas/administração & dosagem , Antígenos de Plantas/química , Arachis/química , Arachis/imunologia , Linfócitos B/imunologia , Linfócitos B/patologia , Estudos de Casos e Controles , Epitopos/imunologia , Sequenciamento de Nucleotídeos em Larga Escala , Ensaios de Triagem em Larga Escala , Humanos , Proteínas de Membrana/administração & dosagem , Proteínas de Membrana/química , Hipersensibilidade a Amendoim/genética , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/patologia , Biblioteca de Peptídeos , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/química , Medicina de Precisão , Proteínas de Armazenamento de Sementes
18.
J Oleo Sci ; 70(11): 1631-1640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34732635

RESUMO

Reducing allergenicity and increasing oleic content are important goals in groundnut breeding studies. Ara h 1 is a major allergen gene and Delta(12)-fatty-acid desaturase (FAD2) is responsible for converting oleic into linoleic acid. These genes have homoeologues with one copy in each subgenome, identified as Ara h 1.01, Ara h 1.02, ahFAD2A and ahFAD2B in tetraploid groundnut. To alter functional properties of these genes we have generated an Ethyl Methane Sulfonate (EMS) induced mutant population to be used in Targeting Induced Local Lesions in Genomes (TILLING) approach. Seeds were exposed to two EMS concentrations and the germination rates were calculated as 90.1% (1353 plants) for 0.4% and 60.4% (906 plants) for 1.2% EMS concentrations in the M1 generation. Among the 1541 M2 mutants, 768 were analyzed by TILLING using four homoeologous genes. Two heterozygous mutations were identified in the ahFAD2B and ahFAD2A gene regions from 1.2% and 0.4% EMS-treated populations, respectively. The mutation in ahFAD2B resulted in an amino acid change, which was serine to threonine predicted to be tolerated according to SIFT analysis. The other mutation causing amino acid change, glycine to aspartic acid was predicted to affect protein function in ahFAD2A. No mutations were detected in Ara h 1.01 and Ara h 1.02 for both EMS-treatments after sequencing. We estimated the overall mutation rate to be 1 mutation every 2139 kb. The mutation frequencies were also 1/317 kb for ahFAD2A in 0.4% EMS and 1/466 kb for ahFAD2B in 1.2% EMS treatments. The results demonstrated that TILLING is a powerful tool to interfere with gene function in crops and the mutagenized population developed in this study can be used as an efficient reverse genetics tool for groundnut improvement and functional genomics.


Assuntos
Antígenos de Plantas/genética , Arachis/genética , Arachis/metabolismo , Ácidos Graxos Dessaturases/genética , Genoma de Planta/genética , Proteínas de Membrana/genética , Proteínas de Plantas/genética , Mutação Puntual , Genética Reversa/métodos , Alérgenos/metabolismo , Arachis/imunologia , Ácido Linoleico/metabolismo , Ácido Oleico/metabolismo , Hipersensibilidade a Amendoim/prevenção & controle
19.
Clin Immunol ; 230: 108820, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34365017

RESUMO

BACKGROUND: Peanut oral immunotherapy (POIT) has provided desensitization to peanut allergic individuals. Limited immunological evaluation exists during the first 24-weeks of POIT. OBJECTIVE: Regulatory T-cells (Tregs) are antigen induced immunosuppressive T-cells important in establishing tolerance. Delineation of early immunologic changes contributing to the development of peanut desensitization would help clarify the mechanism of action in POIT. We performed single-cell RNA sequencing (scRNAseq) on Tregs in pediatric subjects undergoing POIT during the first 24-weeks of therapy to evaluate early immunological changes induced by POIT. METHODS: PBMC samples from peanut allergic subjects between 5 and 12 years of age enrolled in a Phase 1/2a POIT study were collected and analyzed at 0, 6, and 24-weeks after POIT initiation and samples were compared to healthy non-peanut allergic controls. Tregs were enriched from PBMCs and scRNAseq analysis performed. Cell Ranger 3.1.0 (10× Genomics) was utilized to identify cell clusters and differentially expressed genes, and results were analyzed with Seurat suite version 3.0.0. RESULTS: Gene analysis revealed 10 major clusters corresponding to different cell types observed to change during POIT when compared to the healthy, non-peanut-allergic state. scRNAseq analysis of Tregs revealed strong CD3G expression correlating with gdTregs. scRNAseq analysis of gdTregs revealed dynamic changes occurring within the first 6-weeks of treatment and cell frequencies of naïve and memory gdTregs at 24-weeks of treatment reducing to levels similar to healthy controls. Analysis of transcriptomic cell identity analysis using SingleR showed gene expression in gdTregs similar to healthy control after 24-weeks of POIT treatment. scRNAseq analysis revealed alterations in gene expression for memory and naïve gdTregs during this timeframe. Specifically, expression of OX40R (TNFRSF4), GITR (TNFRSF18), TGFB1, CTLA4, ISG20, CD69 were upregulated in memory gdTregs compared to naive gdTregs by 24-weeks of POIT, while IL7R and SELL were downregulated in memory gdTregs compared to naïve gdTregs. CONCLUSIONS: There are specific expression profiles of peripheral naïve and mature gdTreg cells in peanut allergic patients undergoing POIT in the first 24-weeks of treatment implicating pathways involved in maintenance of immune homeostasis. gdTreg cells may contribute to the tolerogenic effect of POIT within the first 24-weeks of POIT treatment. These findings suggest that gdTregs cells may be an early marker of desensitization in subjects undergoing POIT.


Assuntos
Arachis/imunologia , Dessensibilização Imunológica/métodos , Genes Codificadores da Cadeia delta de Receptores de Linfócitos T , Genes Codificadores da Cadeia gama de Receptores de Linfócitos T , Hipersensibilidade a Amendoim/terapia , Linfócitos T Reguladores/imunologia , Administração Oral , Alérgenos/administração & dosagem , Criança , Pré-Escolar , Humanos , Memória Imunológica , Família Multigênica , Hipersensibilidade a Amendoim/genética , Hipersensibilidade a Amendoim/imunologia , RNA-Seq , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Análise de Célula Única , Fatores de Tempo , Transcriptoma
20.
Nutrients ; 13(7)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34371828

RESUMO

There is increasing evidence that early introduction of allergenic foods may decrease the risk of developing IgE-mediated food allergy. Patterns of food introduction before the 2015 publication of the Learning Early about Peanut Allergy (LEAP) trial are not well-studied, but are important as a baseline for evaluating subsequent changes in infant feeding practices and potentially food allergy. We performed a retrospective longitudinal study using data from a multicenter cohort of infants hospitalized with bronchiolitis between 2011-2014. The primary outcomes were IgE-mediated egg or peanut allergy by age 3 years. Of 770 participants included in the analysis, 635 (82%) introduced egg, and 221 (27%) introduced peanut by age 12 months per parent report. Four participants had likely egg allergy, and eight participants had likely peanut allergy by age 3 years. Regular infant egg consumption was associated with less egg allergy. The association was suggestive for infant peanut consumption with zero peanut allergy cases. Overall, our results suggest that early introduction of peanut was uncommon before 2015. Although limited by the small number of allergy cases, our results suggest that early introduction of egg and peanut are associated with a decreased risk of developing food allergy, and support recent changes in practice guidelines.


Assuntos
Alérgenos/administração & dosagem , Dieta/métodos , Ingestão de Alimentos/imunologia , Hipersensibilidade Alimentar/imunologia , Fenômenos Fisiológicos da Nutrição do Lactente/imunologia , Alérgenos/imunologia , Arachis/imunologia , Pré-Escolar , Dieta/efeitos adversos , Hipersensibilidade a Ovo/epidemiologia , Hipersensibilidade a Ovo/imunologia , Ovos , Feminino , Hipersensibilidade Alimentar/epidemiologia , Humanos , Imunoglobulina E/imunologia , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Hipersensibilidade a Amendoim/epidemiologia , Hipersensibilidade a Amendoim/imunologia , Estudos Retrospectivos
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