Conservation Analysis of B-Cell Allergen Epitopes to Predict Clinical Cross-Reactivity Between Shellfish and Inhalant Invertebrate Allergens.

Roni Nugraha,Shaymaviswanathan Karnaneedi,Andreas L Lopata,Thimo Ruethers,Sandip D Kamath,Elecia Johnston

doi:10.3389/fimmu.2019.02676

Abstract

Understanding and predicting an individual's clinical cross-reactivity to related allergens is a key to better management, treatment and progression of novel therapeutics for food allergy. In food allergy, clinical cross-reactivity is observed in patients reacting to unexpected allergen sources containing the same allergenic protein or antibody binding patches (epitopes), often resulting in severe allergic reactions. Shellfish allergy affects up to 2% of the world population and persists for life in most patients. The diagnosis of shellfish allergy is however often challenging due to reported clinical cross-reactivity to other invertebrates including mites and cockroaches. Prediction of cross-reactivity can be achieved utilizing an in-depth analysis of a few selected IgE-antibody binding epitopes. We combined available experimentally proven IgE-binding epitopes with informatics-based cross-reactivity prediction modeling to assist in the identification of clinical cross-reactive biomarkers on shellfish allergens. This knowledge can be translated into prevention and treatment of allergic diseases. To overcome the problem of predicting IgE cross-reactivity of shellfish allergens we developed an epitope conservation model using IgE binding epitopes available in the Immune Epitope Database and Analysis Resource (http://www.iedb.org/). We applied this method to a set of four different shrimp allergens, and successfully identified several non-cross-reactive as well as cross-reactive epitopes, which have been experimentally established to cross-react. Based on these findings we suggest that this method can be used for advanced component-resolved-diagnosis to identify patients sensitized to a specific shellfish group and distinguish from patients with extensive cross-reactivity to ingested and inhaled allergens from invertebrate sources.

Highlights

The prevalence of food allergy is steadily increasing over the past decade, with ∼4% of adults and up to 10% of children having some type of food allergy
The dataset for the subsequent analysis was built from available IgE binding epitopes from four shrimp allergens: tropomyosin (TM), arginine kinase (AK), myosin light chain (MLC), and sarcoplasmic calcium-binding protein (SCBP)
Four shrimp allergens, TM, AK, SCP, and MLC were selected based on the availability of the IgE-binding epitopes

Summary

Introduction

The prevalence of food allergy is steadily increasing over the past decade, with ∼4% of adults and up to 10% of children having some type of food allergy. It is estimated that 2% of the general population are affected by food allergy to shellfish [2]. Similar to peanut allergy, one of the highest rates of food-induced anaphylaxis with nearly 42% among affected adults and 12% in children [3]. Subsequent exposure to the shellfish allergen, via ingestion or inhalation, triggers the generation of specific IgE antibodies by activated B-cells of the immune system. These antibodies subsequently bind to immune effector cells, including mast cells and basophils, resulting in degranulation and clinical manifestation of allergic symptoms [5]. Eight proteins from different shellfish species are known as the main provocateur of shellfish allergy and have been registered in the World Health Organization and International Union of Immunological Societies (WHO/IUIS) Allergen Nomenclature Sub-committee [2]

Methods

Results

Discussion

Conclusion