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This document is a research paper discussing the diagnosis of hypersensitivity to amoxicillin, a type of beta-lactam antibiotic. The authors conducted a study using a test called hMC-pMAT to evaluate its effectiveness in diagnosing amoxicillin hypersensitivity. The results showed that hMC-pMAT was comparable to other diagnostic tests, such as the basophil activation test (BAT), in clear cases of hypersensitivity. However, in more difficult cases and in patients with non-responsive basophils, hMC-pMAT did not provide additional value. The authors suggest that further research is needed to validate and generalize these findings, especially for patients with non-responsive basophils. [Extracted from the article]

Background Methods Results Conclusion Few studies have examined long‐term outcomes following oral immunotherapy (OIT); none have examined long‐term risks and benefits associated with distinct clinical outcomes (desensitization, remission).Participants completing the probiotic and peanut oral immunotherapy (PPOIT) ‐003 randomized trial were enrolled in a follow‐on study, PPOIT‐003LT. Peanut ingestion, reactions, and health‐related quality of life (HRQOL) were monitored prospectively. Outcomes at 1‐year and 2‐years post‐treatment were examined by treatment group and by post‐OIT clinical outcome (remission, desensitization without remission [DWR], allergic).86% (151/176) of eligible children enrolled. Post‐treatment peanut ingestion at 2‐years post‐treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2‐years post‐treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI −0.03, 0.20), p = .127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD −0.21 (95%CI −0.39; −0.03), p = .02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p = .001) participants. At 2‐years post‐treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD −0.54 (95%CI −0.99, −0.10), p = .017) and allergic (MD −0.82 (95%CI −1.25, −0.38), p < .001).By 2‐years post‐treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient‐preferred treatment outcome over desensitization or remaining allergic. [ABSTRACT FROM AUTHOR]

Peanut allergy, a prevalent and potentially severe condition affecting millions worldwide, has been linked to specific human leukocyte antigens (HLAs), suggesting increased susceptibility. Employing an immunoinformatic strategy, we developed a "logo model" based on amino acid frequencies in the peptide binding core and used it to predict peptides originating from 28 known peanut allergens binding to HLA-DRB1*03:01, one of the susceptibility alleles. These peptides hold promise for immunotherapy in HLA-DRB1*03:01 carriers, offering reduced allergenicity compared to whole proteins. By targeting essential epitopes, immunotherapy can modulate immune responses with minimal risk of severe reactions. This precise approach could induce immune tolerance with fewer adverse effects, presenting a safer and more effective treatment for peanut allergy and other allergic conditions. [ABSTRACT FROM AUTHOR]

This article explores the differences in mast cell activation between anaphylaxis and desensitization in human peanut allergy. The study used human mast cells and sera from peanut-allergic individuals to investigate the functional differences in mast cell activation after anaphylaxis and desensitization. The findings suggest that desensitization reduces the overall activation and release of interleukin 8 (IL-8) compared to anaphylaxis. The study also found that refractoriness, or temporary antigen-specific resistance, occurs independently of the initial activation modality. Further research is needed to understand the immune response to allergen-specific immunotherapy in vivo. [Extracted from the article]

Food allergy (FA) is a potentially life‐threatening chronic condition that is becoming an increasing public health problem worldwide. This systematic review (SR) was carried out to inform the development of clinical recommendations on the treatment of IgE‐mediated FA with biologics and/or IT for the update of the EAACI guidelines. A SR of randomized‐controlled trials or quasi‐controlled trials was carried out. Studies were identified via comprehensive search strategies in Medline, Embase, and Cochrane Library, up to April 2022. Population: Human adults, children, and adolescents with IgE‐mediated FA. Intervention: IT and/or biologics. Comparator: Placebo or standard‐of‐care (allergen avoidance). Outcome: Efficacy (desensitization, sustained unresponsiveness (SU), remission), quality of life, and safety (systemic and local adverse reactions (AR)). The Cochrane RoB tool was used to assess the risk of bias. It was reported according to PRISMA and registered in PROSPERO CRD4202229828. After screening, 121 studies were included (111 for IT and 10 for biologics). Most studies had a high risk of bias and showed high heterogeneity in design and results. Metanalysis showed a positive effect of biologics and IT in terms of relative risk (RR) for achieving tolerance to the culprit food compared to avoidance or placebo. Omalizumab for any FA showed a RR of 2.17 [95% confidence interval: 1.22, 3.85]. For peanut allergy, oral IT (OIT) had a RR of 11.94 [1.76, 80.84] versus avoidance or placebo, sublingual IT (SLIT) had a RR of 3.00 [1.04, 8.66], and epicutaneous IT (EPIT) of 2.16 [1.56, 3.00]. OIT had a RR of 5.88 [2.27, 15.18] for cow's milk allergy, and of 3.43 [2.24, 5.27] for egg allergy. There was insufficient data on SLIT or EPIT for the treatment of egg and milk allergies. Most ARs reported were mild. For OIT the most common AR involved the gastrointestinal system and for EPIT, AR's most commonly affected the skin. There was limited data on severe or life‐threatening ARs. There was limited evidence for long term efficacy and quality of life. In conclusion, biologics and IT, alone or in combination, are effective in achieving desensitization while on active treatment but more evidence is needed on long‐term tolerance as current evidence is not of high quality. Adverse events while on therapy are generally mild to moderate but a long‐term comprehensive safety profile is missing. There is a critical need to optimize and standardize desensitization protocols and outcome measures to facilitate our understanding of the efficacy and safety as well as to allow for comparison between interventions. [ABSTRACT FROM AUTHOR]

This article discusses a study on sunflower seed allergy, specifically focusing on the allergenicity of seed-storage 2S-albumins found in sunflower seeds. The study found that patients allergic to sunflower seeds were also sensitized to certain proteins, which were found to be more potent in triggering allergic reactions. The study suggests that IgE sensitization to these proteins may be a marker of clinical severity in sunflower seed allergy. Further research is needed to evaluate the allergenicity of other proteins in sunflower seeds. The study was supported by SOFIPROTEOL as part of the FASO PRODIAL project, and the authors declare no conflicts of interest. [Extracted from the article]

This article explores the emergence of lupin as a potential hidden food allergen. The true prevalence of lupin allergy is currently unknown, but the Allergy-Vigilance Network® (AVN) reported 62 cases of lupin-induced anaphylaxis out of 2,708 cases of food-induced anaphylaxis from 2002 to 2020. The study found that lupin-induced anaphylaxis was more common in females, adults, individuals with a peanut allergy, and after consuming prepacked food products. The research also revealed a significant degree of cross-reactivity between lupin and other legumes, particularly peanut. The authors recommend that allergists be aware of lupin cross-reactivity and that patients with a history of food anaphylaxis be tested for lupin. [Extracted from the article]

This document summarizes a study on the relationship between atopic dermatitis (AD) and IgE-mediated food allergy (FA) in children. The study found that children with AD were more likely to develop FA, and vice versa. However, the study had limitations, such as not assessing the severity of AD and having a small sample size for cases of FA. The findings suggest that AD and FA may be related and further research is needed to understand and address these conditions. [Extracted from the article]

The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized Collaborative Cross strain CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, in contrast to C3H/HeJ (C3H) mice. This study aimed to determine the genetic basis of orally induced anaphylaxis to peanut in CC027 mice. A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 mice and 5 additional Collaborative Cross strains. Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis and 4% having severe anaphylaxis. There were 8 genetic loci associated with variation in response to peanut challenge—6 associated with anaphylaxis (temperature decrease) and 2 associated with peanut-specific IgE levels. There were 2 major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Themis gene. Consistent with described functions of Themis , we found that CC027 mice have more immature T cells with fewer CD8+, CD4+, and CD4+CD25+CD127− regulatory T cells. Our results demonstrate a key role for Themis in the orally reactive CC027 mouse model of peanut allergy. [ABSTRACT FROM AUTHOR]

Objective: To study the differences in allergen sensitization of parents and their offspring with respiratory allergic diseases. Methods: We included parents and their children who were both diagnosed with allergic asthma and/or allergic rhinitis, between January 2018 and December 2022. Parent-child dyads were evaluated for sensitization to six categories of allergens viz, dust mite, fungus, animal dander, weed pollen, tree pollen and food allergen, by measuring the allergen-specific immunoglobulin E levels (sIgE). Data of gender, age, feeding history, serum total IgE (tIgE), and absolute eosinophil counts (AEC) were collected and analyzed for differences in allergen sensitization of parents and children. Results: Overall, the AEC in children were significantly higher than that of parents. The sensitivity to fungal allergens in children was significantly higher than that in fathers (33.3% vs 6.7%, P = 0.01) as well as mothers (29.3% vs 8.3%, P = 0.03). Sensitization to food allergens was also higher in children compared to fathers (25.4% vs 7.9%, P = 0.01). Fathers with tree pollen allergen sensitivity, and mothers with weed pollen allergen sensitivity had a significantly increased risk (aOR, 95% CI) of having increased sensitivity to these allergens in their offspring; 24.01 (1.08, 53.99; P = 0.04) and 3.27 (1.08, 9.92; P = 0.04), respectively. Conclusion: Children had greater sensitivity for fungal allergens compared to both parents, as well as food allergy compared to fathers. Fathers with tree pollen allergen sensitivity, and mothers with weed pollen allergen sensitivity had an increased risk of having their children sensitive to these types of allergens [ABSTRACT FROM AUTHOR]

The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post‐diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random‐effects dose–response meta‐analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all‐cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease‐free events). Meta‐analyses, including 3–10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega‐3 polyunsaturated fatty acids, supplemental calcium, circulating 25‐hydroxyvitamin D (25[OH]D) and all‐cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer‐specific mortality; and for circulating 25(OH)D and recurrence/disease‐free survival. The overall evidence was graded as 'limited'. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant‐based foods), whole grains, total, caffeinated, or decaffeinated coffee and all‐cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all‐cause mortality provided 'limited—suggestive' evidence. All other exposure‐outcome associations provided 'limited—no conclusion' evidence. Additional, well‐conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors. [ABSTRACT FROM AUTHOR]

Summary Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE‐ and non‐IgE‐mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE‐ and non‐IgE‐mediated food allergies and considers the potential future investigations in this context. [ABSTRACT FROM AUTHOR]

Summary The last few decades have seen striking changes in the field of food allergy. The prevalence of the disease has risen dramatically in many parts of the globe, and management of the condition has undergone major revision. While delayed introduction of common allergenic foods during infancy was advised for many years, the learning early about peanut allergy (LEAP) trial and other studies led to a major shift in infant feeding practices, with deliberate early introduction of these foods now recommended. Additionally, the Food and Drug Administration approved the first treatment for food allergy in 2020—a peanut oral immunotherapy (OIT) product that likely represents just the beginning of new immunotherapy‐based and other treatments for food allergy. Our knowledge of the environmental and genetic factors contributing to the pathogenesis of food allergy has also undergone transformational advances. Here, we will discuss our efforts to improve the clinical care of patients with food allergy and our understanding of the immunological mechanisms contributing to this common disease. [ABSTRACT FROM AUTHOR]

The article discusses a study on mice that explores the development of allergies to egg white after exposure to house dust mite (HDM). The study suggests that exposure to HDM through the airways can lead to sensitization to egg proteins and the development of food allergies. The article also mentions other studies that investigate the expression of certain molecules in different types of asthma in mice, the different pathways involved in house dust mite-induced allergic disease in the upper and lower airways, and how molecular recognition of allergens shapes innate responses to house dust mite allergens. These articles provide valuable insights into the mechanisms and pathways involved in asthma and allergic diseases. [Extracted from the article]

Food allergy (FA) is estimated to impact up to 10% of the population and is a growing health concern. FA results from a failure in the mucosal immune system to establish or maintain immunological tolerance to innocuous dietary antigens, IgE production, and the release of histamine and other mediators upon exposure to a food allergen. Of the different FAs, peanut allergy has the highest incidence of severe allergic responses, including systemic anaphylaxis. Despite the recent FDA approval of peanut oral immunotherapy and other investigational immunotherapies, a loss of protection following cessation of therapy can occur, suggesting that these therapies do not address the underlying immune response driving FA. Our lab has shown that liver-directed gene therapy with an adeno-associated virus (AAV) vector induces transgene product-specific regulatory T cells (Tregs), eradicates pre-existing pathogenic antibodies, and protects against anaphylaxis in several models, including ovalbumin induced FA. In an epicutaneous peanut allergy mouse model, the hepatic AAV co-expression of four peanut antigens Ara h1, Ara h2, Ara h3, and Ara h6 together or the single expression of Ara h3 prevented the development of a peanut allergy. Since FA patients show a reduction in Treg numbers and/or function, we believe our approach may address this unmet need. [ABSTRACT FROM AUTHOR]

Background: There are no studies of longitudinal immunoglobulin measurements in a population‐based cohort alongside challenge‐confirmed peanut allergy outcomes. Little is known about biomarkers for identifying naturally resolving peanut allergy during childhood. Objectives: To measure longitudinal trends in whole peanut and component Ara h 2 sIgE and sIgG4 in the first 10 years of life, in a population cohort of children with challenge‐confirmed peanut allergy, and to determine whether peanut‐specific immunoglobulin levels or trends are associated with peanut allergy persistence or resolution by 10 years of age. Methods: One‐year‐old infants with challenge‐confirmed peanut allergy (n = 156) from the HealthNuts study (n = 5276) were prospectively followed at ages 4, 6, and 10 years with questionnaires, skin prick tests, oral food challenges, and plasma total‐IgE, sIgE and sIgG4 to peanut and Ara h 2. Results: Peanut allergy resolved in 33.9% (95% CI = 25.3%, 43.3%) of children by 10 years old with most resolving (97.4%, 95% CI = 86.5%, 99.9%) by 6 years old. Decreasing Ara h 2 sIgE (p =.01) and increasing peanut sIgG4 (p <.001), Ara h 2 sIgG4 (p =.01), peanut sIgG4/sIgE (p <.001) and Ara h 2 sIgG4/sIgE (p <.001) from 1 to 10 years of age were associated with peanut allergy resolution. Peanut sIgE measured at 1 year old had the greatest prognostic value (AUC = 0.75 [95% CI = 0.66, 0.82]); however, no single threshold produced both high sensitivity and specificity. Conclusion: One third of infant peanut allergy resolved by 10 years of age. Decreasing sIgE and sIgG4 to peanut and Ara h 2 over time were associated with natural resolution of peanut allergy. However, biomarker levels at diagnosis were not strongly associated with the natural history of peanut allergy. [ABSTRACT FROM AUTHOR]

(1) Peanut allergy is associated with high risk of anaphylaxis which could be prevented by oral immunotherapy. Patients eligible for immunotherapy are selected on the basis of a food challenge, although currently the assessment of antibodies against main peanut molecules (Ara h 1, 2, 3 and 6) is thought to be another option. (2) The current study assessed the relationship between the mentioned antibodies, challenge outcomes, skin tests and some other parameters in peanut-sensitized children. It involved 74 children, divided into two groups, based on their response to a food challenge. (3) Both groups differed in results of skin tests, levels of component-specific antibodies and peanut exposure history. The antibody levels were then used to calculate thresholds for prediction of challenge results or symptom severity. While the antibody-based challenge prediction revealed statistical significance, it failed in cases of severe symptoms. Furthermore, no significant correlation was observed between antibody levels, symptom-eliciting doses and the risk of severe anaphylaxis. Although in some patients it could result from interference with IgG4, the latter would not be a universal explanation of this phenomenon. (4) Despite some limitations, antibody-based screening may be an alternative to the food challenge, although its clinical relevance still requires further studies. [ABSTRACT FROM AUTHOR]

This article discusses the development of a potential immunotherapy treatment for peanut allergy. The researchers conjugated peanut extract with galactomannan, a higher molecular weight saccharide, to reduce the allergenicity of the extract. They found that the conjugated extract, known as PE-GM, showed reduced reactivity with IgE antibodies and basophil activation in patients with peanut allergy. In a mouse model, PE-GM also demonstrated a lower anaphylactic response compared to untreated mice. These findings suggest that PE-GM could be a safer and more effective treatment option for peanut allergy. [Extracted from the article]

Background: Allergy to peanuts and tree nuts is a common cause of food allergy in Spain, with lipid transfer proteins (LTP) being the most frequently recognized panallergen. LTP sensitization often leads to multiple food group sensitivities, resulting in overly restrictive diets that hinder patient's quality of life. This study aimed to assess the tolerance of peanuts and tree nuts (hazelnuts and walnuts) in children sensitized to LTP, potentially mitigating the need for such diets. Methods: This prospective study enrolled individuals diagnosed with allergy to peanuts, hazelnuts, or walnuts. Data were collected from medical records, including demographics and clinical history. Allergological assessment comprised skin prick tests using commercial extracts and the nuts in question, alongside measurements of total and specific IgE to nuts and their primary molecular components. Participants showing positive LTP sensitization without sensitization to seed storage proteins underwent open oral nut challenges. Results: A total of 75 individuals labeled as allergic to peanuts, 44 to hazelnuts, and 51 to walnuts were included. All of them underwent an open oral provocation test with the incriminated nut, showing a high tolerance rate. Peanut was tolerated by 98.6% of patients, 97.72% tolerated hazelnut, and 84.3% tolerated walnut. Conclusion: The findings suggest that the majority of patients allergic to peanuts, hazelnuts, or walnuts, due to LTP sensitization and lacking IgE reactivity to seed storage proteins, can tolerate these nuts. This supports the need for personalized nut tolerance assessments to avoid unnecessary dietary restrictions. [ABSTRACT FROM AUTHOR]

This article examines the occurrence of anaphylaxis in children undergoing oral immunotherapy (OIT) for cow's milk and egg allergies. The study found that 38.1% of patients experienced anaphylaxis during OIT, with a higher rate in cow's milk OIT compared to egg OIT. Most cases of anaphylaxis were mild or moderate and successfully treated with medication. Only one patient had severe anaphylaxis but recovered with prompt treatment. A significant number of patients who experienced anaphylaxis discontinued the treatment, but the achievement of desensitization was similar between those with and without anaphylactic reactions. The study emphasizes the importance of education and additional therapies to improve adherence and outcomes in OIT. [Extracted from the article]

Background: Few studies have assessed the nature of accidental allergic reactions (AAR). We assessed the prevalence and risk factors for AAR in Japanese children. Methods: This study included children with immediate‐type hen's egg (HE), cow's milk (CM), wheat, or peanut allergy who developed allergic reactions within at least 2 years and were followed up regularly at a single national allergy center in Japan. From January to December 2020, low‐dose reactivity was defined as allergic reactions to ≤250, ≤102, ≤53, or ≤ 133 mg of HE, CM, wheat, or peanut protein, respectively. The annualized AAR rate showed the number of reactions per patient per year (95% confidence interval). AAR risk factors were analyzed using multiple logistic regression. Results: Of the 1096 participants, 609, 457, 138, and 90 had HE, CM, wheat, and peanut allergies, respectively. The median (interquartile range) age was 5.0 (2.3–8.6) years, 39% had completely eliminated allergenic food, and 24% had low‐dose reactivity. The annualized AAR rate was 0.130 (0.109–0.153) in all sub‐cohorts. Moderate and severe symptoms occurred in 50% and 0.7%, respectively, of children who experienced AAR. Multiple logistic regression revealed that low‐dose reactivity was a significant risk factor for AAR in the overall and CM cohorts, respectively (p <.001 and p =.036). Conclusion: In this single‐center study in Japan, the annualized AAR rate was relatively low during the COVID‐19 pandemic; however, half of the participants with AAR had moderate to severe symptoms. Especially in the case of low‐dose reactivity, children would require careful AAR risk management. [ABSTRACT FROM AUTHOR]

Low-dose oral food challenge (LD-OFC) is an approach to avoid complete elimination in high-risk patients with wheat allergy (WA). We examined the 3-year prognosis after LD-OFC among patients who passed and failed LD-OFC. Children with immediate-type WA aged ≤6 years with a history of reaction to ≤390 mg of wheat protein underwent their first LD-OFC with 52 mg (baseline LD-OFC). After passing the LD-OFC, children stepped up to 390, 1300, and 5200 mg step-by-step every 3–6 months. After failing LD-OFC, children repeated LD-OFC every 6–12 months. We assessed wheat tolerance defined as consuming 5200 mg without symptoms for 3 years after baseline LD-OFC. The median age of 124 children was 2.4 years, and the wheat- and ω-5-gliadin-specific immunoglobulin E (IgE) levels (kU A /L) were 23.6 and 2.1, respectively. Upon baseline LD-OFC, 57% passed (LD-tolerant), whereas 43% failed (LD-reactive). Within 3 years, 38% of the LD-reactive group passed re-administered LD-OFC, and 70% of all participants avoided complete elimination. The percentage of the participants who became capable of consuming 390 mg (87% vs. 18%), 1300 mg (78% vs. 13%), and acquired tolerance (70% vs. 13%) was significantly higher in the LD-tolerant group than in the LD-reactive group (p < 0.001). Predictors of persistent WA in the LD-tolerant group were older age (adjusted odds ratio, 1.63), ω-5-gliadin-specific IgE level (1.62 per 10-fold increase), and other food allergies (1.94). LD-tolerant patients frequently acquired wheat tolerance within 3 years. Even if once positive, one-third could pass the re-administered LD-OFC within 3 years. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: IgE-mediated peanut allergy is an important public health problem of increasing prevalence leading to anaphylactic reactions both in children and adults. Allergen-specific oral immunotherapy (OIT) is the single treatment with the potential capacity to modify the course of the disease, but it still faces some drawbacks in terms of efficacy, safety, patients' adherence, and cost. Alternative strategies, including the use of novel adjuvants, to overcome such limitations are highly demanded. The main aim of this study was to search for potential novel adjuvants for peanut OIT by assessing the capacity of free purified mannan and different toll-like receptor ligands (TLR-Ls) to immunomodulate the responses of human monocyte-derived dendritic cells (hmoDCs) to peanut allergens. Methods: Monocytes were isolated from PBMCs of healthy donors and differentiated into hmoDCs. Flow cytometry, ELISA, coculture, and suppression assay were performed to assess the effects of TLR-Ls, mannan, and crude peanut extract (CPE) in hmoDCs. Results: Purified free mannan increased the expression levels of HLA-DR, CD86, CD83, and PD-L1 and induced a higher IL-10/IL-6 cytokine ratio in hmoDCs compared to the stimulation with different TLR-Ls. Mannan significantly increased the expression of HLA-DR, the maturation marker CD83, the tolerogenic marker PD-L1, as well as the production of IL-10, IL-6, and TNF-α in CPE-stimulated hmoDCs. Supporting these tolerogenic properties, mannan also significantly increased the frequency of FOXP3+ regulatory T cells generated by CPE-treated hmoDCs with functional suppressive capacity. Conclusions: We uncover that purified free mannan induces tolerogenic responses in human DCs stimulated with peanut allergens, suggesting mannan as a suitable potential novel adjuvant to be exploited in the context of OIT for peanut allergy. [ABSTRACT FROM AUTHOR]

Background: Palforzia® enables the safe and effective desensitisation of children with peanut allergy. The treatment pathway requires multiple visits for dose escalation, up‐dosing, monitoring of patients taking maintenance therapy and conversion onto daily real‐world peanut consumption. The demand for peanut immunotherapy outstrips current National Health Service (NHS) capacity and requires services to develop a national consensus on how best to offer Palforzia® in a safe and equitable manner. We undertook a Delphi consensus exercise to determine guidance statements for the implementation of Palforzia®‐based immunotherapy in the NHS. Methods: We undertook focus groups with children and young people who had received peanut immunotherapy to assess what was important for them and their carers. Common themes from patients formed the basis of creating draft statements. A panel of 18 multi‐disciplinary professionals engaged in two rounds of anonymised voting to adapt the statements and score their importance. A final consensus workshop consolidated any variation in comments and scores to develop the final guidance statements. Results: The panel achieved consensus on 91% (29/32) of guidance statements, demonstrating strong consensus around pragmatic principles for assuring the integrity of consent, safety and conversion from Palforzia® to real‐world peanut products. The greatest amount of feedback was generated from three broad issues; (i) whether eligibility assessment should include compulsory peanut challenges and whether these should be designed to assess the threshold at which patients react to peanut, (ii) the governance processes to best ensure that patients' interests are prioritised and (iii) how to safely transition young people to other services, or discharge them, while they are taking daily peanut. Conclusions: This consensus highlights the urgent need for the NHS to increase capacity for undertaking diagnostic food challenges as well as developing Palforzia® immunotherapy pathways. The voting panel agreed that families of peanut allergic children should be made aware of immunotherapy, that eligibility assessment should include how co‐morbid conditions are managed and that services should monitor for adverse effects. The finalised statements are now published online for clinical practice in the UK. These guidance statements will be adapted in the coming years as more evidence is published and as the international experience of peanut immunotherapy evolves. [ABSTRACT FROM AUTHOR]

Background: In 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. Methods: We 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. Results: The percentage of infantile peanut introduction was 4.9% (n = 3,294), 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. Conclusion: In countries with a low prevalence of PA, the effect of infantile peanut introduction on PA prevention was unclear. [ABSTRACT FROM AUTHOR]