Report from AAAAI 2019

This weekend’s annual scientific meeting of the American Academy of Allergy, Asthma & Immunology features hundreds of research presentations, many of which provide noteworthy new findings in the field of food allergy. FARE staff are attending the San Francisco conference along with thousands of allergists, immunologists, researchers and other healthcare providers. Here are highlights from some of Saturday’s presentations focusing on the food allergy field.

• Red Meat Allergy May Develop Independent of Tick Blood Meal Status: Delayed allergic reactions to eating non-primate mammalian meats like beef, pork and venison has been on the rise in recent years. This emerging disease, called alpha-gal syndrome (AGS), is associated with the bites of some but not all tick species. Most mammalian meats contain a sugar called alpha-gal, which is a known human allergen that binds IgE antibodies from individuals with AGS. In the proposed primary mechanism of transmission, a tick bites a non-human mammal and takes in a blood meal containing alpha-gal, then bites a human and subsequently injects some of that alpha-gal while feeding, leading to human sensitization. New research presented at AAAAI 2019 by Scott P. Commins, MD, PhD, and colleagues explored whether tick saliva alone can induce AGS independent of the need for a preexisting blood meal. Basophils, immune cells that participate in allergic reactions, were exposed to plasma (including IgE antibodies) from healthy individuals and from patients allergic to alpha-gal and then were treated with extract from salivary glands of various ticks. For cells exposed to IgE from AGS patients, Lone Star tick salivary gland extract increased basophil activation 40-fold. IgE from patients with AGS reacted with tick saliva, but not with tick larvae extract or tick salivary gland extract. The reactivity of Lone Star tick saliva may indicate that alpha-gal allergen is present in these ticks even in the absence of a blood meal, suggesting higher risk for human sensitization by tick bites.

• A 5-year Summary of Real-life Dietary Egg Consumption after Completion of a 4-year Egg OIT Protocol: This study by Edwin Kim, MD, and others investigated the long-term dietary impact of egg oral immunotherapy (OIT). Forty egg-allergic patients ages 5-11 received egg OIT for up to four years, while 15 received placebo for one year. Egg OIT recipients who passed a 10g oral food challenge were considered desensitized, and those who tolerated a second 10g challenge and open feeding 4-6 weeks after discontinuing therapy were found to exhibit sustained unresponsiveness (SU). At the end of the clinical trial, half of OIT subjects were classified as SU, 28 were desensitized, and 22 percent were not desensitized. For five years following trial completion, yearly follow-up questionnaires assessed participants’ egg consumption and symptoms. At year 5, 93 percent of OIT recipients were ingesting some egg, compared to 64 percent of placebo recipients; this high rate of egg consumption among those who received placebo may reflect children outgrowing their egg allergy. Everyone in the SU group who submitted questionnaires ate both concentrated and baked egg, compared to 43 percent of the desensitized group, 17 percent of the not-desensitized group, and 36 percent of the placebo group. Compared to the SU group, all of the non-SU groups ate less egg, less often, and had more symptoms in response. Three non-SU subjects required epinephrine after eating concentrated egg. Further study is needed to develop biomarkers that can help doctors predict treatment response to OIT, limit treatment risks and assess clinical outcomes.

• Successful Desensitisation and Sustained Unresponsiveness Using Modified Peanut: Results From the BOPI Study: The BOPI study is a Phase 2b/3 clinical trial led by Paul Turner, PhD, to assess efficacy and safety of boiled peanut oral immunotherapy (bpOIT). Boiling peanut modifies the proteins and makes them less allergenic but still capable of inducing desensitization. Forty-seven children (8-17 years) with confirmed peanut allergy either took bpOIT for 6 months, followed by 6 months of maintenance with roasted peanut, or continued avoiding peanut. Compared to one early withdrawal from the peanut avoidance group of 8, eight withdrew from the active group of 32, with four leaving due to adverse events. Of the 24 who completed the active protocol, all were desensitized to tolerate a 1.4g peanut protein challenge, which was roughly ten times the average dose that elicited a reaction prior to treatment. Nearly 60 percent (14/24) were able to tolerate 4.4 g peanut protein after the year of treatment and maintenance, and more than half (13/24) achieved sustained unresponsiveness, able to consume 4.4g peanut protein four weeks after the end of treatment. By comparison, the average eliciting dose for the peanut avoidance control group did not change. Ten patients experienced a total of 19 episodes of anaphylaxis during home dosing. Fewer than 2 percent of doses were associated with gastrointestinal symptoms.

• Changes in Whole Blood Transcriptome during Peanut-Induced Anaphylaxis and Correlation with Symptoms: We don’t know why IgE-mediated reactions cause anaphylaxis in some cases but not in others. Researchers including Paul Turner, PhD, and Jonathan Spergel, MD, PhD, analyzed blood samples taken from 37 adults and 57 children during double-blind, placebo-controlled peanut challenges to compare patterns of gene expression to reaction severity. Anaphylaxis, as defined by National Institute of Allergy and Infectious Disease criteria, occurred in 31 adults (84 percent) and 27 children (47 percent), with 17 children and 17 adults having lower respiratory symptoms. Twenty of the subjects who experienced anaphylaxis underwent at least one further challenge during which milder, non-anaphylactic symptoms occurred. Significant changes in gene expression were seen two hours after a reaction but not immediately before a challenge or during a reaction. This implies that acute reactions likely result from the release of preformed mediators, rather than changes in gene expression. Gene expression did not differ significantly between anaphylaxis reactions involving only the skin and gut and non-anaphylactic reactions. Notably, anaphylaxis involving the larynx, trachea, bronchi or lungs was associated with significantly altered expression of 22 genes. This suggests that anaphylactic reactions involving laryngeal and/or lower respiratory symptoms have a different pathophysiology than reactions limited to gut and skin symptoms, which are not considered food-induced anaphylaxis according to criteria used in the United Kingdom and Australia.

• Epidemiology of Sesame Allergy in the United States: To estimate the current prevalence and severity of sesame allergy in the U.S., nearly 52,000 households comprising 79,000 individuals of all ages completed questionnaires during 2015-2016. Strict criteria were used to distinguish symptoms of probable IgE-mediated sesame allergy from food intolerances and oral allergy syndrome. Results were weighted to maximize precision. Ruchi S. Gupta, MD, MPH, and colleagues found that sesame is the ninth most common food allergy, affecting an estimated 0.3 percent of individuals in the U.S. (that is, three cases of sesame allergy for every 1,000 U.S residents). Prevalence appears to have increased over the past decade. Sesame allergy is most common among young adults ages 18-29, followed by ages 30-39. Higher income ($50,000 or more per year) was associated with greater odds of having sesame allergy. Sesame often elicits severe allergic reactions characterized by serious symptoms and multiple organ system involvement: more than one-third of sesame-allergic individuals had experienced at least one severe reaction to sesame, and one-third had been seen in the emergency department for a sesame reaction.

Stay tuned for more highlights from this year’s AAAAI meeting on the FARE blog.