Global patterns in anaphylaxis due to specific foods: a systematic review
Background: There are increasing global data relating to prevalence of food allergy and food-induced anaphylaxis, however this is often based on surrogate measures of sensitization rather than objective symptoms at food challenge. In terms of protecting food-allergic consumers from reactions, there has been no global survey assessing geographical differences in the proportion of anaphylaxis triggered by specific foods.
Objective: To identify common triggers for food-induced anaphylaxis, and how these vary from country to country.
Methods: Systematic review of relevant reports published between January 2010 and November 2020. Results were reported following PRISMA guidelines. Publications were screened and data extracted by two independent reviewers, and risk of bias assessed.
Results: Sixty-five studies (encompassing 41 countries and all 6 regions as defined by the Food & Agriculture Organization of the United Nations) were included. Significant regional variations in the most common triggers of food-anaphylaxis were seen, however, in general there was good agreement between local legislative requirements for allergen disclosure and the commonest allergens for each region/nation.
Conclusions: Local legislation for allergen disclosure generally reflect those allergens commonly responsible for food-anaphylaxis. Cow's milk and crustaceans appear to cause a higher proportion of anaphylaxis compared to peanut in some regions.
Onset of nut allergy in a pediatric cohort: clinical and molecular patterns. AFRUSEN study
Background: Nut allergy is a growing problem, but little is known about its onset in children.
Objective: Characterize the onset of nut allergy in Southern European children.
Methods: Consecutive patients up to 14years of age who presented to allergy departments with an initial allergic reaction to peanut, tree nut, or seed were included. An allergy workup including clinical history, food challenge, SPT, and whole-extract sIgE and ImmunoCAP 112-ISAC assay were performed.
Results: Of the 271 children included, 260 were first diagnosed with nut allergy at age 6.5years, 11.8(±21.2SD) months after the index reaction. The most common culprit nuts at onset were walnut (36.5%), peanut (28.5%), cashew (10.4%), hazelnut (8.5%), pistachio (5.4%), and almond (5%). Peanut-allergy onset was more frequent in children ≤6y.o. and walnut in those >6y.o. (p=0.032). In 65% of cases, the allergic reaction occurred the first time the patient consumed the nut, and 35% of reactions were anaphylactic. Overall, nut polysensitization was detected by SPT in 64.9% of patients, though this rate was lower among walnut- (54.7%) and peanut (54.1%)-allergic children (p<0.0001). Sensitization to 2S albumins was predominant (75%), specially Jug r1 (52.8%), whereas LTPs was less relevant (37%).
Conclusion: In our population, the onset of nut allergy occurred around 6years of age, slightly later than that reported in Anglo-Saxon countries. Walnut was the main trigger, followed by peanut and 2S albumins storage proteins, especially Jug r1, are the most relevant allergens. This study will help guide management and may contribute to preventive strategies in pediatric nut allergy.
https://doi.org/10.18176/jiaci.0696
Unbiased Immunization Strategy Yielding Specific Nanobodies against Macadamia Allergen of Vicilin-like Protein for Immunoassay Development
Macadamia nut contains important food allergens that potentially cause allergic reactions with severe adverse effects in infants and adults. Reliable and accurate detection of macadamia is critical to avoid allergic reactions. However, knowledge on macadamia allergen is scarce and a reliable detection method has not been reported, yet. In this study, an unbiased immunization and selection strategy was employed to select nanobodies (Nbs) recognizing specifically macadamia allergen, as well as to establish a detection method to unveil a macadamia protein contamination. An alpaca was immunized with a crude protein extract of macadamia followed by construction of a Nb library from its lymphocytes. The panning and screening of this immune Nb repertoire resulted in the selection of six target-specific Nbs. Nb-mediated immuno-capturing combined with mass spectrometry allowed us to identify the target as the macadamia vicilin-like antimicrobial peptides 2-3 (MiAMP2), a novel food allergenic protein abbreviated as Mac i 1. Later on, an immunoassay of a heterologous sandwich ELISA method based on the selected Nb-pairs was established, providing a linear response in the range of 0.442-2,800 μg/mL and with a limit of detection of 27.1 ng/mL. The dedicated immunoassay has been verified by detecting the antigen spiked in food samples. Our study provided evidence for the successful application of the unprejudiced strategy to retrieve Nbs against a priori undefined macadamia allergen. These target-specific Nbs were used to design a highly reliable and effective immunoassay.
ImmunoCAP ISAC in food allergy diagnosis: a systematic review of diagnostic test accuracy
The aim of this systematic review is to assess the diagnostic test accuracy of the component-resolved diagnosis device ImmunoCAP ISAC, compared with oral food challenge. Systematic review reported according to the PRISMA-DTA recommendations. Medline, Embase and Cochrane Library databases were searched from inception to May 2019 and updated in March 2021. We included diagnostic test accuracy studies comparing ISAC component results as the index test with oral food challenge as the reference test, in people of any age suspected of IgE-mediated food allergy to milk, egg, peanut, shrimp, hake, apple, peach, kiwi, melon, walnut, hazelnut, wheat or pineapple. Risk of bias was evaluated using the QUADAS-2 tool. We screened 799 titles and included 11 studies - seven prospective and two retrospective cohort studies, two case-control studies. Included studies evaluated IgE to Gald1 (three studies, 300 participants, 140 with egg allergy), Bosd5 (three studies, 242 participants, 146 with milk allergy) and Arah1 or 2 (seven studies, 546 participants, 346 with peanut allergy). No studies were identified for other ISAC components. Risk of bias was high or unclear mainly due to inadequate blinding. Applicability was of high or unclear concern due to unclear thresholds, inappropriate exclusions and variable populations. Gald1 sensitivity ranged from 58 to 84%, specificity 87%-97%. Bosd5 sensitivity 24%-40%, specificity 94%-95%. Arah1 sensitivity 45%-91%, specificity 41%-93%. Arah2 sensitivity 70%-94%, specificity 75%-95%. Diagnostic test accuracy information for ISAC components was only available for milk, egg and peanut. Specificity is generally higher than sensitivity, which contrasts with the performance of skin prick and standard specific IgE tests for diagnosing food allergy. Higher quality information is needed to determine the clinical utility of ISAC for food allergy diagnosis.
Oral food challenge in IgE mediated food allergy in eastern Mediterranean children
Background: The oral food challenge (OFC) in IgE mediated food allergy causes anxiety both in parents and in patients due to its inherent risks.
Objective: Documentation of the rate, spectrum, and predictors of positive reactions is instructive.
Methods: Children, who underwent OFC between January 1, 2017 and December 31, 2019 were analyzed.
Results: A total of 1361 OFCs in 613 cases were reviewed. Most of them were performed in preschool children (≤2 years 50%) and 55% of them had more than one OFC. Mainly considered food groups were cow's milk (31.8%), hen's egg (28.5%), tree nuts (20%), legumes (7%), seeds (4.9%), and wheat (2.7%). The overall OFC positivity was 9.6%, whereas 6.7% with cow's milk, 4.9% with hen's egg, 16.1% with tree nuts, 21.6% with wheat, and 32.8% with seeds. The severity scoring revealed grade I (24.4%), II (45.8%), and III (29.7%) reactions. Fifty (38%) cases required epinephrine and four cases required hospitalization. OFCs with sesame seeds (odds ratio [OR]: 7.747, [confidence interval (CI) 95%: 4.03-14.90]), wheat (OR: 3.80, [CI: 1.64-8.84]), and tree nuts (OR: 2.78, [CI: 1.83-4.23]) predicted a positive OFC while a concomitant asthma (OR: 3.61 [CI: 1.27-10.28]) was more likely to elicit anaphylaxis.
Conclusion: In OFC practice, priority is given to basic nutritional sources and the most frequent food allergens, where preschool children with multiple sensitizations are the primary subjects. Increased risks of positive reactions with sesame, tree nut, and wheat and increased risk of anaphylaxis with concomitant asthma should be considered while performing OFC.
A Practical, Stepwise Approach to Peanut Oral Immunotherapy in Clinical Practice: Benefits and Risks
Food allergies are common, affecting 6-8% of the children in the United States. There is a significant burden on the quality of life of allergic children and their caregivers, due to multiple dietary, social and psychological restrictions. Peanut allergy affects approximately 2-5% of the school-age children. Despite the recommended dietary avoidance, reactions tend to occur due to unintentional exposures and the fear of accidental ingestions potentially resulting in anaphylaxis and death, which creates a lot of anxiety in peanut-allergic individuals. Peanut oral immunotherapy (POIT) has emerged as a form of active treatment and has shown high efficacy in research trials with the majority of participants achieving desensitization and protection from trace exposures. An improved quality of life has also been noted following successful POIT. The risks of POIT should be balanced against the benefits resulting from successful treatment for each individual. Rates of allergic reactions and anaphylaxis are reported to be higher in individuals pursuing therapy, but most subjects will experience mild or moderate reactions during treatment. The landscape of peanut allergy management is changing and the future offers more options for patients than were previously available. Shared decision-making, which is the process of how to choose between different available options, becomes an ongoing discussion between the clinician and the patient, which will ensure achievement of the best possible outcome for the peanut-allergic child. This is a multistep process that evaluates the benefits and risks of therapy or no therapy, as well as patient and family preferences and we review it in detail in this manuscript with the aim to provide clinicians with a practical approach.
https://doi.org/10.2147/JAA.S290915
Multi-dimensional study of the oral microbiome, metabolite, and immunologic environment in peanut allergy
Background: The oral mucosa is the initial interface between food antigens, microbiota and mucosal immunity, yet little is known about oral host-environment dynamics in food allergy.
Objective: To determine oral microbial, metabolic, and immunologic profiles associated with peanut allergy.
Methods: We recruited 105 subjects (peanut allergic n=56, healthy subjects n=49) for salivary microbiome profiling using 16S rRNA sequencing, short chain fatty acid (SCFA) metabolite assays using liquid chromatography/mass spectrometry, and measurement of oral secreted cytokines using multiplex assays. Analyses within and across data types were performed.
Results: The oral microbiome of peanut-allergic individuals was characterized by reduced species in Lactobacillales, Bacteroidales (Prevotella), and Bacillales, and increased Neisseriales spp. The distinct oral microbiome of peanut-allergic subjects was accompanied by significant reductions of oral SCFA levels, including acetate, butyrate, and propionate, and significant elevation of IL-4 secretion. Decreased abundances of oral Prevotella spp. and Veillonella spp. in peanut-allergic subjects were significantly correlated with reduced oral SCFA levels (FDR<0.05), and increased oral Neisseria spp. was correlated with lower oral SCFA levels (FDR<0.05). Additionally, oral Prevotella spp. abundances were correlated with decreased local secretion of Th2-stimulating epithelial factors (IL-33, TSLP) and Th2 cytokines (IL-4, IL-5, IL-13), while oral Neisseria spp. abundance was positively associated with a Th2-skewed oral immune milieu.
Conclusion: Our novel multi-dimensional analysis of the oral environment revealed distinct microbial and metabolic profiles associated with mucosal immune disturbances in peanut-allergy. Our findings highlight the oral environment as an anatomical site of interest to examine host-microbiome dynamics in food allergy.
https://doi.org/10.1016/j.jaci.2021.03.028
Emerging developments in the forefront of peanut oral immunotherapy
Purpose of review: Despite the COVID-19 pandemic, progress continued in the field of peanut oral immunotherapy over the past 12 to 18 months. Of importance, the first oral immunotherapy product for the treatment of peanut allergy was approved by the US Food and Drug Administration in January 2020.
Recent findings: Suggested modifications to the practice of oral immunotherapy, some of which may have lasting impacts, were circulated as a result of the pandemic. New advances in pathophysiology, sustained unresponsiveness, quality of life, safety, and cost effectiveness were also published.
Summary: During 2020, COVID-19 influenced the daily practice of allergy and immunology, with peanut oral immunotherapy being no exception. However, clinicians now have a FDA-approved treatment option for peanut allergy in children, a welcome development for a difficult disease. Future research is needed to clarify several knowledge deficits surrounding the best use of peanut OIT.