IgE-sensitization toward AK has been found in 10–51% of shrimp allergic patients ( 2). TM has been identified as a major allergen in over 14 crustacean and 5 mollusc species ( Meanwhile, AK has been considered as the second invertebrate pan-allergen, implicating allergy cross-reactivity to shellfish, mite and insect. Tropomyosin is the major allergen of shellfish allergy with specific IgE antibody responses in 60–80% of shellfish allergic patients recognizing this protein, and it is suggested to be a good biomarker of severe clinical-reactivity to shellfish ( 6, 7). Two allergens of major importance in the development of shellfish allergy are the muscle protein tropomyosin (TM) and the enzyme arginine kinase (AK). Currently, 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). These antibodies subsequently bind to immune effector cells, including mast cells and basophils, resulting in degranulation and clinical manifestation of allergic symptoms ( 5). In the sensitized individual, 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. Shellfish allergy is typically persistent, with only 13% of patients likely to outgrow their shellfish allergy ( 4). Shellfish allergy has, similar to peanut allergy, one of the highest rates of food-induced anaphylaxis with nearly 42% among affected adults and 12% in children ( 3). It is estimated that 2% of the general population are affected by food allergy to shellfish ( 2). The shellfish group is included among the “Big Eight” food groups that are responsible for more than 90% of all food allergy cases ( 1). 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. 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. 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. 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 ( ). This knowledge can be translated into prevention and treatment of allergic diseases. 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. Prediction of cross-reactivity can be achieved utilizing an in-depth analysis of a few selected IgE-antibody binding epitopes. The diagnosis of shellfish allergy is however often challenging due to reported clinical cross-reactivity to other invertebrates including mites and cockroaches. Shellfish allergy affects up to 2% of the world population and persists for life in most patients. 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. 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. 4Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, VIC, Australia.3Department of Aquatic Product Technology, Bogor Agricultural University, Bogor, Indonesia.2Department of Molecular and Cell Biology, College of Public Health, Medical and Veterinary Science, James Cook University, Townsville, QLD, Australia.1Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, Australia.Kamath 1,2,4 Elecia Johnston 1,2 Shaymaviswanathan Karnaneedi 1,2,4 Thimo Ruethers 1,2,4 Andreas L.
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