Definition and mechanism
Statistical data indicate that the extent of food allergy cases accounts for approximately 1% to 2% of the total population, and it often occurs in infants (1 to 3 y of age) whose immune systems have not yet been well developed and children (Taylor and Hefle 2001). Food allergens exist widely in various food products. More than 90% of food allergies are derived from 8 types of food including cow milk, eggs, fish, crustaceans (shrimp, crab, and lobster, and so on), peanuts, soybeans, tree nuts (almond, walnut, cashew, pistachio, and hazelnut, and so on), and wheat. These 8 food categories have been defined as the most important types causing food allergies by the Food and Agriculture Organization of the United Nations (FAO 1995). Among them, food allergy to cow milk, eggs, and peanuts often occurs in infants under 3 y of age, accounting for approximately 6% to 8%, while the occurrence of an allergy triggered by nuts and seafood showed a higher proportion in adults, with approximately 1% to 2% adults having allergies to peanuts, tree nuts, and seafood (Sampson 1996; Sicherer and others 1999; Grundy and others 2002; Untersmayr and Jensen-Jarolim 2006). The symptoms in 80% of children allergic to cow milk, eggs, soy, and wheat are relieved before reaching school age, while the allergies to peanuts, tree nuts, and seafood typically persist throughout life (Sicherer and Sampson 2006). The statistical analyses showed that the occurrence of food allergy is rising, indicating that food allergy is a major issue that cannot be ignored (Sicherer and others 2010).
All abnormal physiological responses caused by diet are collectively defined as food sensitivity, which can be divided into food allergy, which is regulated by the immune system, and food intolerance, which is not regulated by the immune system (Figure 1). Food allergy is the abnormal evoked response in the immune system caused by specific components in the food, and these components are usually the proteins naturally occurring, which are nontoxic and show no adverse effects for most individuals. Based on the characteristics of the immune response, it can be divided into 2 types of reactions: the IgE-mediated immediate hypersensitivity reaction regulated by immunoglobulin IgE; and the non-IgE-mediated delayed hypersensitivity reaction. For the former, after ingestion of the allergenic food, the symptoms arise usually in a few minutes to 1 h, or even right after the moment of ingestion. The abnormal immune response is generated by the antigen-specific IgE in the humoral immune system, which is the most common food allergy and has been most widely investigated. The latter usually occurs within 6 to 24 h after ingestion, and the probability of occurrence is relatively low and with an unclear mechanism. The latter belongs to an abnormal immune response generated by sensitive T cells in the cellular immune response (Taylor and others 2000). The abnormal response of food intolerance is not caused by the immune system. For example, metabolic food disorders are genetic defects in the ability to metabolize certain food ingredients (such as lactose intolerance) or an increased sensitivity to certain food ingredients because of a genetic defect (such as favism). An anaphylactoid reaction is caused by the sensitizing factor released from mast cells and basophils. It is difficult to distinguish from the immediate food allergy regulated by IgE in clinical practice. The only difference is that an anaphylactoid reaction is not IgE-regulated. The pathogenic mechanism of idiosyncratic reaction such as sulfite-induced asthma in some individuals is poorly understood (Taylor and others 1992).
Clinical studies have confirmed that, among all abnormal immune responses caused by food, the proportion of those regulated by IgE is the highest. The allergic reactions caused by allergenic foods such as cow milk, eggs, seafood, and nuts belong to this category. Therefore, the investigations of food allergies have primarily focused on the food allergies regulated by IgE (Taylor and others 1992). The reaction mechanism of a food-induced allergy can be divided into 5 stages: recognizing the antigen; generating immunoglobulin IgE; activating the mast cells and basophils; releasing the sensitizing factors; and presenting the clinical symptoms. When a sensitive individual ingests an allergenic food, the allergen protein in this food is recognized by the immune system as an antigen, and an allergic reaction is induced. When T cells are stimulated by the antigen, they release the substances IL-4, IL-5, and IL-13 to activate and convert B cells into plasma cells that can secret IgE. IgE with specificity to the particular allergen will bind to the receptors of the mast cells and basophils so that they are activated to be sensitive cells. When the allergen is ingested into the body again, the allergen will be recognized as the antigen and binding to the IgE on the surface of the mast cells and basophils, resulting in the degranulation of particles and the release of the vesicles containing the sensitizing factors. These sensitizing factors are then released into the blood and interact with the receptors on cells and tissues, thereby causing the symptoms of an allergic reaction. The allergic symptoms caused by food allergy and their severity depend on the individual physical conditions and the intake amount, which may be moderate, severe, and even life-threatening symptoms in the gastrointestinal tract, the skin, or the respiratory tract (Untersmayr and Jensen-Jarolim 2006).
The pathogenesis of food allergy, including what makes one person become more allergic than others, and the factors that make some foods and food proteins more allergenic than other foods and food proteins are still unknown. No perfect treatment for food allergy is currently available (Mills and others 2009). The food allergy reaction regulated by IgE has quite a low tolerance to specific foods, and trace amounts are sufficient to cause an allergic reaction in some sensitive individuals. Therefore, sensitive individuals must avoid the ingestion of foods that cause an abnormal reaction. Food allergy sufferers must wear medical identification, fully understand their own condition, carry medications at all times, and learn emergency treatments such as self-injection of epinephrine in the early stage of allergy symptoms to avoid more serious consequences. Attention should also be paid to the incomplete cleaning of processing equipment and eating utensils as well as cross-contamination during meal preparation. In addition, patients with food allergies should carefully read the labels on packaged foods in order to avoid what must not be ingested (Taylor and others 1992; Sicherer and Sampson 2010). The 2003/13/EC of the European Union stipulates that foods containing grains (gluten), crustaceans, eggs, fish, peanuts, soybeans, cow milk, nuts, celery, mustard, sesame, and sulfites (if more than 10 mg/kg or 10 mg/L) must be labeled (EU 2003). The allergen-labeling specifications of the United Kingdom and Australia are similar to those of the European Union (Food Standards Agency 2006; Australian Food and Grocery Council 2007). In January 2006, the U.S. FDA announced the Food Allergen Labeling and Consumer Protection Act (FALCPA), which specifies the labeling of allergenic foods and products sold in the United States, including cow milk, eggs, fish, crustaceans, peanuts, tree nuts, wheat, and soybeans. The label text is required to be clear and easy to understand; for example, “milk” instead of its specific ingredient “casein.” If casein is used as a term, it must be followed by an explanation in plain text such as “casein (milk).” In Asia, according to the enforcement rules of the Food Sanitation Law by the Ministry of Health, Labor and Welfare of Japan, the labels of foods that would likely lead to an allergic reaction are divided into 2 categories: mandatory and recommended labels. Eggs, cow milk, peanuts, wheat, buckwheat, shrimp, and crab require mandatory labeling by ministerial ordinance and are referred to as “specific allergenic ingredients” (Akiyama and others 2011). On the other hand, foods that require only recommended labeling include ingredients such as abalone, squid, salmon roe, kiwifruit, beef, walnut, soybean, apple, and peach, referred to as “subspecific allergenic ingredients.” In P. R. China, the Chinese Natl. Food Safety Standard stipulates labeling for 8 categories of prepackaged foods that easily lead to allergies. If any of these categories are used as ingredients or might be added during the food processing, then they must be listed among the ingredients or nearby on the label (Ministry of Health of the People's Republic of China 2011).
Seafood includes a wide variety of foods: fish such as cod, salmon, and tuna; crustaceans such as shrimp, crab, and lobster; and mollusks such as oysters, abalone, squid, scallops, and clams. Crustaceans and mollusks can be collectively defined as shellfish. Seafood allergies often occur in areas geographically adjacent to an ocean. The allergy symptoms caused by seafood range widely from minor urticaria to severe life-threatening symptoms. The epidemiological statistics indicate that approximately 6.6 million people, accounting for 2.3% of the population in the United States, have a seafood allergy (Sicherer and others 2004). With increasing age, the chance of seafood ingestion gradually increases; therefore, the cases of seafood allergy mostly occur in adults. Moreover, the people with a shellfish allergy are the majority in the population, with an incidence 5 times higher than those with fish allergy. The major allergen of fish is parvalbumin, with a molecular weight of 12 kDa, while that of shellfish is mainly tropomyosin, with a molecular weight of 36 to 39 kDa, which often causes an allergic reaction after ingestion (Lopata and others 2010).