Peanut challenges prior to oral immunotherapy demonstrate high tolerance rates in selected patients
Background: Peanut oral immunotherapy (pOIT) protocols typically remain below the threshold for reaction during the initial dose escalation (IDE) day. However, some patients may have higher thresholds for reaction or may not have an ongoing peanut allergy. Objective: We sought to characterize the response to an accelerated initial dose escalation (A-IDE) for qualifying low-risk peanut-allergic patients younger than 4 years in which IDE progressed to a full peanut oral food challenge as tolerated. Methods: Records of 76 pOIT patients younger than 4 years were reviewed. Those with history of peanut reaction with peanut allergy testing of less than 95% positive predictive value for failed oral food challenge were offered an A-IDE. A-IDE proceeded stepwise until patients refused dosing, any reaction occurred, or they tolerated the challenge (cumulative dose: 4000 mg peanut protein). If the A-IDE was not tolerated, patients completed pOIT. Results: From April 2022 to February 2024, 16 patients participated in an A-IDE. Eleven (68.8%) tolerated the 4000 mg cumulative dose, demonstrating resolution of their peanut allergy. The remaining had mild symptoms not requiring epinephrine. Mean pOIT starting dose following A-IDE was 450 mg (vs 25 mg in standard pOIT). Maintenance dosing was reached with a mean of 5.2 visits (vs 9.7 in standard pOIT). Conclusions: Nearly 70% of low-risk patients younger than 4 years with previous diagnosis of peanut allergy tolerated a full peanut serving when initiating pOIT. This indicates the importance of diagnostic peanut challenge to selected patients before initiating OIT.
https://doi.org/10.1016/j.jacig.2025.100442
Ara h 2-expressing cucumber mosaic virus-like particle (VLP Peanut) induces in vitro tolerogenic cellular responses in peanut-allergic individuals
Background: Peanut allergy (PA) is one of the most prevalent food allergies with a lack of favorable safety/efficacy treatment. A cucumber mosaic virus-like particle expressing peanut allergen component Ara h 2 (VLP Peanut) has been developed as a novel therapeutic approach for PA. Objective: We assessed the tolerogenic properties and reactivity of VLP Peanut. Methods: Whole blood and peripheral blood mononuclear cells were collected from 6 peanut-allergic children. Modulation of dendritic cells (DCs), T cells, and B cells, stimulated with VLP Peanut, Ara h 2, and whole peanut extract in vitro, were assessed by quantitative real-time PCR and flow cytometry, respectively. Basophil and skin reactivity in response to VLP Peanut was assessed by basophil activation test and skin prick test, respectively. Results: VLP Peanut showed beneficial biochemical properties, fit for use in clinical studies. VLP Peanut induced IFN-γ+ TH1 (P < .05) while having reduced capacity to elicit proliferation of TH2, allergen-specific TH2, and IL-4+-T follicular helper cells. Moreover, VLP Peanut is associated with upregulation of DC1-associated genes (MX1) compared to Ara h 2 and whole peanut extract. VLP Peanut was the most prominent at inducing IL-10+ regulatory B cells (P < .05). Unbiased clustering analyses identified metaclusters of T and B cells targeted by VLP Peanut. Finally, VLP Peanut had reduced capacity to elicit high- and low-affinity IgE receptor-mediated responses compared to Ara h 2 or whole peanut extract (all P < .05). Finally, in an open-label first-in-human cohort of 6 peanut-allergic adults, administration of increasing concentration of VLP Peanut through skin prick test was tolerated and demonstrated no development of skin reactivity. Conclusions: VLP Peanut displayed tolerogenic properties by modulating DCs, T cells, and B cells in vitro. Preliminary findings of skin reactivity using VLP Peanut in 6 peanut-allergic adults was safe and well tolerated in an open-label phase 1 study.
https://doi.org/10.1016/j.jaci.2024.08.010
Air pollution is associated with persistent peanut allergy in the first 10 years
Background: The role of air pollution in eczema and food allergy development remains understudied. Objective: We aimed to assess whether exposure to air pollution is associated with eczema and food allergies in the first 10 years of life. Methods: HealthNuts recruited a population-based sample of 1-year-old infants who were followed up at ages 4, 6, and 10 years. Annual average fine particulate matter (particulate matter with diameter of 2.5 μm or less, or PM2.5) and nitrogen dioxide (NO2) exposures were assigned to geocoded residential addresses. Eczema was defined by parent report. Oral food challenges to peanut, egg, and sesame were used to measure food allergy. Multilevel logistic regression models were fitted, and estimates were reported as adjusted odds ratios. Results: Those exposed to high concentration of NO2 (<10 ppb) at age 1 year had higher peanut allergy prevalence at ages 1 (adjusted odds ratio [95% confidence interval], 2.21 [1.40-3.48]) and 4 (2.29 [1.28-4.11]) years. High exposure to NO2 at 6 years old were associated with higher peanut allergy prevalence at age 6 (1.34 [1.00-1.82] per 2.7 ppb NO2 increase) years. Similarly, increased PM2.5 at age 1 year was associated with peanut allergy at ages 4, 6, and 10 years (respectively, 1.27 [1.01-1.60], 1.27 [1.01-1.56], and 1.46 [1.05-2.04] per 1.2 μg/m PM2.5 increase) years. We found that increased concentrations of NO2 or PM2.5 at age 1 year were associated with persistent peanut allergy at later ages. Little evidence of associations was observed with eczema or with egg allergy. Conclusions: Early-life exposure to PM2.5 and NO2 was associated with peanut allergy prevalence and persistence. Policies aiming at reducing air pollution could potentially reduce presence and persistence of peanut allergy.
https://doi.org/10.1016/j.jaci.2024.08.018
Prevalence and Determinants of Food Allergy in the Era of Early Allergen Introduction: the EarlyNuts Population-Based Study
Background: Infant feeding guidelines in Australia changed in 2016 to recommend introducing common allergy-causing foods by age 1 year to prevent food allergy. Although most Australian infants now eat peanut and egg by age 6 months, some still develop food allergy despite the early introduction of allergens. Objectives: To describe the prevalence of food allergy in a cohort recruited after introducing the nationwide allergy prevention recommendations; identify characteristics of infants who developed allergy despite early introduction of allergens; and estimate the causal effect of modifiable exposures on food allergy prevalence and whether this differed between infants who were introduced to allergens before or after age 6 months. Methods: We recruited a population-based sample of 12-month-old infants in Melbourne, Australia. Infants had skin prick tests to four foods and parents completed questionnaires. Infants with evidence of sensitization were offered oral food challenges. Prevalence estimates were adjusted using inverse probability weighting. Results: In a cohort of infants (n = 1,420) in which nearly all infants had been introduced to common allergens such as egg, milk, and peanut by age 1 year, the prevalence of food allergy remained high at 11.3% (95% CI, 9.6-13.4). Infants who developed food allergy despite introduction of the allergen by age 6 months were more likely to have Asian-born parents. Early-onset moderate or severe eczema was associated with an increased odds of food allergy irrespective of whether allergens were introduced before or after age 6 months. Among infants who were introduced to peanut at age 6 months or earlier, antibiotic use by age 6 months was associated with an increased odds of peanut allergy (adjusted odds ratio = 6.03; 95% CI, 1.15-31.60). Conclusions: In a cohort in which early allergen introduction was common, the prevalence of food allergy remained high. Infants who developed food allergy despite introduction of the respective allergen by age 6 months were more likely to have had Asian parents and early-onset eczema. New interventions are needed for infants with a phenotype of food allergy that is not amenable to early allergen introduction. https://doi.org/10.1016/j.jaip.2024.07.001
Saliva antibody profiles are associated with reaction threshold and severity of peanut allergic reactions
Background: Reaction threshold and severity in food allergy are difficult to predict, and there is a lack of non-invasive predictors. Objectives: We sought to determine the relationships between pre-challenge levels of peanut (PN)-specific antibodies in saliva and reaction threshold, severity, and organ-specific symptoms during peanut allergic reactions. Methods: We measured PN-specific antibody levels in saliva collected from 127 children with suspected peanut allergy prior to double-blind, placebo-controlled peanut challenges where reaction threshold, severity, and symptoms were rigorously characterized. Low-threshold peanut allergy was defined as reaction to <300mg of peanut protein cumulatively consumed. A consensus severity grading system was used to grade severity. We analyzed associations between antibody levels and reaction threshold, severity, and organ-specific symptoms. Results: Among the 127 children, those with high pre-challenge saliva PN IgE had higher odds of low-threshold peanut allergy (OR 3.9, 95%CI 1.6-9.5), while those with high saliva PN IgA: PN IgE or PN IgG4:PN IgE had lower odds of low-threshold peanut allergy (OR 0.3, 95%CI 0.1-0.8, and OR 0.4, 95%CI 0.2-0.9, respectively). Children with high pre-challenge saliva PN IgG4 had lower odds of severe peanut reactions (OR 0.4, 95%CI 0.2-0.9). Those with high saliva PN IgE had higher odds of respiratory symptoms (OR 8.0, 95%CI 2.2-26.8). Saliva PN IgE modestly correlated with serum PN IgE levels (Pearson r=0.31, P=0.0004). High and low saliva PN IgE levels further distinguished reaction threshold and severity in participants stratified by serum PN IgE, suggesting endotypes. Conclusion: Saliva PN antibodies could aid in non-invasive risk stratification of peanut allergy threshold, severity, and organ-specific symptoms. https://doi.org/10.1016/j.jaci.2024.05.020
Desensitization and remission after peanut sublingual immunotherapy in 1- to 4-year-old peanut-allergic children: A randomized, placebo-controlled trial
Background: Prior studies of peanut sublingual immunotherapy (SLIT) have suggested a potential advantage with younger age at treatment initiation. Objective: We studied the safety and efficacy of SLIT for peanut allergy in 1- to 4-year-old children. Methods: Peanut-allergic 1- to 4-year-old children were randomized to receive 4 mg peanut SLIT versus placebo. Desensitization was assessed by double-blind, placebo-controlled food challenge (DBPCFC) after 36 months of treatment. Participants desensitized to at least 443 mg peanut protein discontinued therapy for 3 months and then underwent DBPCFC to assess for remission. Biomarkers were measured at baseline and longitudinally during treatment. Results: Fifty participants (25 peanut SLIT, 25 placebo) with a median age of 2.4 years were enrolled across 2 sites. The primary end point of desensitization was met with actively treated versus placebo participants having a significantly greater median cumulative tolerated dose (4443 mg vs 143 mg), higher likelihood of passing the month 36 DBPCFC (60% vs 0), and higher likelihood of demonstrating remission (48% vs 0). The highest rate of desensitization and remission was seen in 1- to 2-year-olds, followed by 2- to 3-year-olds and 3- to 4-year-olds. Longitudinal changes in peanut skin prick testing, peanut-specific IgG4, and peanut-specific IgG4/IgE ratio were seen in peanut SLIT but not placebo participants. Oropharyngeal itching was more commonly reported by peanut SLIT than placebo participants. Skin, gastrointestinal, upper respiratory, lower respiratory, and multisystem adverse events were similar between treatment groups. Conclusion: Peanut SLIT safely induces desensitization and remission in 1- to 4-year-old children, with improved outcomes seen with younger age at initiation.
https://doi.org/10.1016/j.jaci.2023.08.032
Defining the window of opportunity and target populations to prevent peanut allergy.
Background: Peanut allergy affects 1% to 2% of European children. Early introduction of peanut into the diet reduces allergy in high-risk infants. Objective: We aimed to determine the optimal target populations and timing of introduction of peanut products to prevent peanut allergy in the general population. Methods: Data from the Enquiring About Tolerance (EAT; n = 1303; normal risk; 3-year follow-up; ISRCTN14254740) and Learning Early About Peanut Allergy study (LEAP; n = 640; high risk; 5-year follow-up; NCT00329784) randomized controlled trials plus the Peanut Allergy Sensitization (PAS; n = 194; low and very high risk; 5-year follow-up) observational study were used to model the intervention in a general population. Peanut allergy was defined by blinded peanut challenge or diagnostic skin prick test result. Results: Targeting only the highest-risk infants with severe eczema reduced the population disease burden by only 4.6%. Greatest reductions in peanut allergy were seen when the intervention was targeted only to the larger but lower-risk groups. A 77% reduction in peanut allergy was estimated when peanut was introduced to the diet of all infants, at 4 months with eczema, and at 6 months without eczema. The estimated reduction in peanut allergy diminished with every month of delayed introduction. If introduction was delayed to 12 months, peanut allergy was only reduced by 33%. Conclusions: The preventive benefit of early introduction of peanut products into the diet decreases as age at introduction increases. In countries where peanut allergy is a public health concern, health care professionals should help parents introduce peanut products into their infants’ diet at 4 to 6 months of life. https://doi.org/10.1016/j.jaci.2022.09.042
The natural history of peanut and egg allergy in children up to age 6 years in the HealthNuts population-based longitudinal study.
Background: prospectively collected data on the natural history of food allergy are lacking. Objective: we examined the natural history of egg and peanut allergy in children from age 1 to 6 years and assessed whether a skin prick test (SPT) result or other clinical factors at diagnosis are associated with the persistence or resolution of food allergy in early childhood. Methods: the HealthNuts cohort consists of 5276 children who were recruited at age 1 year and have been followed prospectively. Children with food allergy at age 1 year (peanut [n = 156] or raw egg [n = 471] allergy ) and children who developed new sensitizations or food reactions after age 1 year were assessed for food sensitization and allergy (confirmed by oral food challenge when indicated) at the 6-year follow-up. Results: new-onset food allergy developed by age 6 years was more common for peanut (0.7% [95% CI = 0.5%-1.1%]) than egg (0.09% [95% CI = 0.03%-0.3%]). Egg allergy resolved more commonly (89% [95% CI = 85%-92%]) than peanut allergy (29% [95% CI = 22%-38%]) by age 6 years. The overall weighted prevalence of peanut allergy at age 6 years was 3.1% (95% CI = 2.6-3.7%) and that of egg allergy was 1.2% (95% = CI 0.9%-1.6%). The factors at age 1 year associated with persistence of peanut allergy were peanut SPT result of 8 mm or larger (odds ratio [OR] = 2.35 [95% CI 1.08-5.12]), sensitization to tree nuts (adjusted OR [aOR] = 2.51 [95% CI = 1.00-6.35]), and early-onset severe eczema (aOR = 3.23, [95% CI 1.17-8.88]). Factors at age 1 associated with persistence of egg allergy at age 6 were egg SPT result of 4 mm or larger (OR = 2.98 [95% CI 1.35-6.36]), other (peanut and/or sesame) food sensitizations (aOR = 2.80 [95% CI = 1.11-7.03]), baked egg allergy (aOR = 7.41 [95% CI = 2.16-25.3]), and early-onset severe eczema (aOR = 3.77 [95% CI = 1.35-10.52]). Conclusion:most egg allergy and nearly one-third of peanut allergy resolves naturally by age 6 years. The prevalence of peanut allergy at age 6 years was similar to that observed at age 1 year, largely owing to new-onset food peanut allergy after age 1 year. Infants with early-onset eczema, larger SPT wheals, or multiple food sensitizations and/or allergies were less likely to acquire tolerance to either peanut or egg. https://doi.org/10.1016/j.jaci.2022.04.008