Clinical Research Poster Abstracts

Although food allergy (FA) is a common, serious health risk in the United States (US), estimates of FA prevalence tend to rely on small and unrepresentative datasets. We use data on millions of privately insured individuals from a proprietary database of private healthcare claims to estimate the prevalence of FA in this population. We estimate the overall prevalence of FA by gender and age over the life course (ages 0-64), as well as the prevalence of specific allergies (peanuts, seafood/shellfish). Generally, FA peaks in childhood and declines through the rest of the life course, but this is not true for all types of FA. For example, the prevalence of seafood/shellfish allergy increases in young adulthood among women.

Background: A passive cutaneous anaphylaxis (PCA) mouse model was utilized to select allergen-specific monoclonal antibody (mAb) cocktails that bind to allergen and prevent binding to specific IgE. These antibodies provided symptomatic relief in individuals with cat or birch allergy as measured by significant reductions in total nasal symptom score (TNSS) following nasal allergen challenge (NAC) and robust suppression of allergen-specific skin prick tests (SPT) relative to baseline in Phase 1 studies.

Objective: To determine if blockade in the PCA mouse model translates to clinical efficacy.

Methods: Mice, humanized for FceR1a, were administered anti-allergen single mAbs, combinations, or an isotype control mAb and then sensitized intradermally with IgE containing baseline plasma from patients in clinical studies evaluating either a single subcutaneous dose of a Fel d 1 mAb cocktail (REGN1908-1909) for cat allergy or a Bet v 1 mAb cocktail (REGN5713-5714-5715) for birch allergy. Mice were subsequently administered cat or birch allergen, respectively, with Evans blue dye. Spectrophotometric dye leakage into tissue was quantified as a measure of mast cell degranulation.

Results: Blockade of mast cell degranulation in the PCA mouse model correlates with the corresponding percent reduction in TNSS after NAC and allergen specific SPT relative to baseline (modest, non-significant correlation for Bet v 1; strong correlation for

Fel d 1: r = 0.7, 0.8 for TNSS and r = 0.9 for SPT, all p ≤ 0.1). Additionally, utilizing logistic regression classification methods, there is modest to good accuracy in predicting TNSS and SPT responses across different thresholds based on the blockade of mast cell degranulation (Bet v 1 and Fel d 1: AUC of ROC curves of 0.67 to 0.94 for TNSS and 0.8 to 0.84 for SPT). Blockade of individual mAbs versus mAb cocktails confirms optimal blocking efficacy of Fel d 1 mAb cocktail (REGN1908-1909) compared with either single mAb; Bet v 1 triple mAb cocktail (REGN5713-5714-5715) compared with single mAb (REGN5715) or dual mAb cocktail (REGN5713-5715).

Conclusions: Blockade of mast cell degranulation in the PCA mouse model correlates to efficacy in clinical settings, validating the model as a useful tool for selection of efficacious anti-allergen therapeutics.

Background: Food allergic reactions can be severe and potentially life threatening and determination of food allergy susceptibility and severity cannot necessarily be predicted based on clinical history. The aim of this study is to integrate bulk RNA-sequencing of human and mouse

peripheral blood mononuclear cells during food allergic reactions and in vivo mouse models of food allergy to identify dysregulated immunological processes associated with severe food allergic reactions.

Methods: Bulk transcriptomics of PBMC’s from human and mouse following food allergic reactions combined with integrative differential expressed gene bivariate and module eigengene network analyses to identify the PBMC transcriptome associated with food allergy severity. In

vivo validation immune cell and gene expression in mice following IgE mediated reaction.

Results: Bulk transcriptomics of PBMC’s from mice with different severity of food allergy identified GO biological processes associated with innate and inflammatory immune responses, dysregulation of MAPK and NFkB signaling and identified 429 genes that correlated with reaction severity. Utilizing a discovery (n = 19) and replication (n = 21) cohort identified 335 genes that correlated with severity of peanut-induced food allergic reactions. Mapping mouse food allergy severity transcriptome onto human transcriptome revealed 11 genes significantly dysregulated and correlated with severity. Analyses of PBMCs revealed rapid change in blood leukocytes particularly inflammatory monocytes (Ly6C hi Ly6G -) and neutrophils that was associated with changes in Clec4e, CD218a and GPR27 surface expression.

Conclusion: Collectively, IgE mediated food allergy severity is associated with a rapid innate inflammatory response associated with acute cellular stress processes and dysregulation of peripheral blood inflammatory myeloid cell frequencies.

Food allergy reactions occur due to an IgE mediated response to a specific consumed food. Reactions vary in severity and can be life threatening. Learning to navigate life with food allergies can be extremely challenging. The food allergy action plan (FAAP) was created to help food allergy patients and families navigate food allergy management. The FAAP serves as a guide on anaphylaxis recognition and epinephrine use. The standard version (s-FAAP) is most commonly distributed in paper format to both patient families, as well as schools and daycares, on a yearly basis.

This project aims to improve the accessibility and portability of the FAAP by introducing the mobile phone friendly food allergy action plan (ph-FAAP). We hypothesize that the s-FAAP is currently underutilized and that introduction of the ph-FAAP could increase accessibility and frequency of use of this important resource.

Oral Immunotherapy (OIT) is a rapidly expanding clinical practice for the management of food allergy in the United States. However, there are no domestic consensus guidelines on the management and practice of OIT, and the implementation of OIT varies widely across various academic and private practice settings. Without a clear consensus on OIT practice, medical education of Allergy trainees in this area is particularly challenging, and few resources exist to guide evaluation and feedback of OIT training.

To address the dearth of OIT medical education resources, a committee of academic Allergist/Immunologists at the University of Michigan iteratively generated a competency-based assessment for OIT. The assessment was modeled on prior competency-based assessments assembled by the American Academy of Allergy, Asthma, and Immunology. Considerations were given toward the longitudinal nature of OIT with specific focus on consenting, updosing, and maintenance phases. Domains of patient safety, fundamental desensitization principles, psychosocial impacts, and practical considerations throughout each OIT phase were included. Special considerations were made to avoid prescriptive competencies and accommodate existing variation in OIT practice.

As OIT grows, the demand for OIT practitioners expands as well. Our hope is that this competency-based assessment increases access to high quality OIT education for Allergy/Immunology trainees.

Introduction: Adult cow’s milk allergy (CMA) is rare, and many report onset after age 18. We present a case of CMA development in an atopic adult after avoidance despite previous negative testing to cow’s milk.

Case Description: A 37-year-old female with a history of atopic dermatitis (AD), filaggrin gene mutation, peanut and tree nut allergy, and systemic lupus erythematosus requested screening for food allergies in the setting of worsening AD. Specific IgE levels (sIgE) to milk, casein, and whey were negative at <0.35 kU/L. Despite previous tolerance, the patient eliminated dairy from her diet. Soon after elimination, her milk skin prick testing (SPT) was negative (1 mm wheal/5 mm flare). After more than 7 months of elimination, she reported perioral hives which occurred 15 minutes after accidental ingestion of baked dairy in pizza crust. She then had facial hives after Romano cheese ingestion. Approximately 18 months into dairy elimination, she developed anaphylaxis after eating a sandwich thought to be dairy-free. Milk and casein SPT following this episode were positive with a 24 mm wheal/65 mm flare and 17 mm wheal/55 mm flare, respectively. These results were confirmed with sIgE (cow’s milk 13.5 kU/L, casein 14.00 kU/L), which remained elevated six months later.

Discussion: Adults often follow elimination diets for reasons other than IgE-mediated food allergy. In contrast to children, there is limited evidence regarding dairy avoidance as a risk factor for adult CMA. This case demonstrates that risk factors for food allergy should be considered prior to diet elimination, especially in atopic adults.