New Insights Seafood, Fish and Shellfish allergy in children
Widodo Judarwanto. Children Allergy Online Clinic, Jakarta Indonesia
The increased consumption of seafood, fish and shellfish has resulted in more frequent reports of adverse reactions to seafood, emphasizing the need for more specific diagnosis and treatment of this condition and exploring reasons for the persistence of this allergy. Interesting and new findings in the area of fish and shellfish allergy. New allergens and important potential cross-reacting allergens have been identified within the fish family and between shellfish, arachnids, and insects. The diagnostic approach may require prick to-prick tests using crude extracts of both raw and cooked forms of seafood for screening seafood sensitization before a food challenge or where food challenge is not feasible. Allergen-specific immunotherapy can be important; mutated less allergenic seafood proteins have been developed for this purpose. Hypersensitive reactions to seafood is one of the most common food allergies. Despite years of intensive studies, the reasons why some people are allergic to seafood is still unclear.
Food allergies affect approximately 3.5-4.0% of the worldwide population. Immediate-type food allergies are mediated by the production of IgE antibodies to specific proteins that occur naturally in allergenic foods. Symptoms are individually variable ranging from mild rashes and hives to life-threatening anaphylactic shock. Seafood allergies are among the most common types of food allergies on a worldwide basis. Allergies to fish and crustacean shellfish are very common.
The persistence of allergy because of seafood proteins’ resistance after rigorous treatment like cooking and extreme pH is well documented. Additionally, IgE antibodies from individuals with persistent allergy may be directed against different epitopes than those in patients with transient allergy. For a topic as important as this one, new areas of technological developments will likely have a significant impact, to provide more accurate methods of diagnosing useful information to patients about the likely course of their seafood allergy over the course of their childhood and beyond.
Fish and shellfish are important in the American diet and economy. Nearly $27 billion are spent each year in the United States on seafood products. Fish and shellfish are also important causes of food hypersensitivity. In fact, shellfish constitute the number one cause of food allergy in the American adult. During the past decade, much has been learned about allergens in fish and shellfish. The major allergens responsible for cross-reactivity among distinct species of fish and amphibians are parvalbumins. The major shellfish allergen has been identified as tropomyosin. Many new and important potential cross-reacting allergens have been identified within the fish family and between shellfish, arachnids, and insects. Extensive research is currently underway for the development of safer and more effective methods for the diagnosis and management of fish and shellfish hypersensitivity.
Seafood plays an important role in human nutrition worldwide, sustained by international trade of a variety of new seafood products. Seafood plays an important role in human nutrition and health. The growing international trade in seafood species and products has added to the popularity and frequency of consumption of a variety of seafood products across many countries. Increased production and consumption have resulted in more frequent reports of adverse reactions, highlighting the need for more specific diagnosis and treatment of seafood allergy. This increased production and consumption of seafood has been accompanied by more frequent reports of adverse health problems among consumers as well as processors of seafood. Adverse reactions to seafood are often generated by contaminants but can also be mediated by the immune system and cause allergies. These reactions can result from exposure to the seafood itself or various non-seafood components in the product.
Non-immunological reactions to seafood can be triggered by contaminants such as parasites, bacteria, viruses, marine toxins and biogenic amines. Ingredients added during processing and canning of seafood can also cause adverse reactions. Importantly all these substances are able to trigger symptoms which are similar to true allergic reactions, which are mediated by antibodies produced by the immune system against specific allergens. Allergic reactions to ‘shellfish’, which comprises the groups of crustaceans and molluscs, can generate clinical symptoms ranging from mild urticaria and oral allergy syndrome to life-threatening anaphylactic reactions. The prevalence of crustacean allergy seems to vary largely between geographical locations, most probably as a result of the availability of seafood.
The major shellfish allergen is tropomyosin, although other allergens may play an important part in allergenicity such as arginine kinase and myosin light chain. Current observations regard tropomyosin to be the major allergen responsible for molecular and clinical cross-reactivity between crustaceans and molluscs, but also to other inhaled invertebrates such as house dust mites and insects.
The most recent prevalence data from Asia highlight seafood as a significant sensitizer in up to 40% of children and 33% of adults. Furthermore, the demonstration of species-specific sensitization to salt-water and fresh-water prawns and processed prawn extract should improve diagnosis. Studies on humans demonstrated for the first time that biologically active fish allergens can be detected in serum samples as early as 10 min after ingestion. These studies highlight that minute amounts of ingested seafood allergens can quickly trigger allergic symptoms; also, inhaled airborne allergens seem to induce sensitization and reactions. In the past 2 years, over 10 additional seafood allergens have been characterized. Allergen-specific detection assays in food products are available for crustacean tropomyosin; however, many specific mollusk and some fish allergens are not readily identified.
Although cross-reactivity between crustacean and mollusks as well as mites is demonstrated, the often poor correlation of IgE reactivity and clinical symptoms calls for more detailed investigations. The recent development of hypoallergenic parvalbumin from carp could form the basis for safer vaccination products for treatment of fish allergy. Molecular characterization of more universal marker allergens for the three major seafood groups will improve current component-resolved clinical diagnosis and have a significant impact on the management of allergic patients, on food labeling and on future immunotherapy for seafood allergy.
Future research on the molecular structure of tropomyosins with a focus on the immunological and particularly clinical cross-reactivity will improve diagnosis and management of this potentially life-threatening allergy and is essential for future immunotherapy.
Molluscan shellfish allergies
Molluscan shellfish allergies are well known but do not appear to occur as frequently. Molluscan shellfish allergies have been documented to all classes of mollusks including gastropods (e.g., limpet, abalone), bivalves (e.g., clams, oysters, mussels), and cephalopods (e.g., squid, octopus). Tropomyosin, a major muscle protein, is the only well-recognized allergen in molluscan shellfish. The allergens in oyster (Cra g 1), abalone (Hal m 1), and squid (Tod p 1) have been identified as tropomyosin. Cross-reactivity to tropomyosin from other molluscan shellfish species has been observed with sera from patients allergic to oysters, suggesting that individuals with allergies to molluscan shellfish should avoid eating all species of molluscan shellfish. Cross-reactions with the related tropomyosin allergens in crustacean shellfish may also occur but this is less clearly defined. Occupational allergies have also been described in workers exposed to molluscan shellfish products by the respiratory and/or cutaneous routes.
With food allergies, one man’s food may truly be another man’s poison. Individuals with food allergies react adversely to the ingestion of foods and food ingredients that most consumers can safely ingest (Taylor and Hefle, 2001). The allergens that provoke adverse reactions in susceptible individuals are naturally occurring proteins in the specific foods (Bush and Hefle, 1996). Molluscan shellfish, like virtually all foods that contain protein, can provoke allergic reactions in some individuals.
Molecular and immunological characterization of shellfish allergens.
Shellfish (crustaceans and mollusks) have long been known as a common cause of allergic reactions to food. Like other food allergies, the allergic reactions to shellfish involve IgE-mediated Type I hypersensitivity. Biochemical and molecular studies have documented the major shrimp allergen is the muscle protein tropomyosin.
Subsequent molecular cloning studies on lobsters and crabs have characterized this protein as the common allergen in crustaceans. There has also been strong immunological evidence that tropomyosin is a cross-reactive allergen among crustaceans and mollusks. This is further confirmed by recent studies on the identification of allergens in squid and abalone.
The advances in the characterization of shellfish allergens will not only enhance our understanding on the physiological basis of shellfish allergy but also lay the groundwork for the development of diagnostic and therapeutic design in food allergies
Molecular identification of the lobster muscle protein tropomyosin as a seafood allergen.
Crustaceans are a major cause of seafood allergy. Recent studies have identified tropomyosin as the major allergen in shrimp. However, such data are lacking in other crustaceans. In the present study lobster allergens were identified and characterized by molecular cloning, sequencing, and expression.
An IgE-reactive complementary DNA clone of 2 kilobase pairs (kb) was identified by screening an expression library of the spiny lobster Panulirus stimpsoni using sera from subjects with crustacean allergy. Expression and sequencing of this clone showed that it has an opening reading frame of 274 amino acids, coding for a 34-kDa protein designated as Pan s I.
The fast muscle tropomyosin from the American lobster Homarus americanus and found that this protein, coined Hom a I, was also recognized by IgE from patients with crustacean allergies. The deduced amino acid sequences of Pan s I and Hom a I, which are the first identified lobster allergens, show significant homology to shrimp tropomyosin. Sera from subjects with crustacean allergies, when preabsorbed with recombinant proteins Pan s I or Hom a I, lost their IgE reactivity to muscle extract of P. stimpsoni and H. americanus. Preincubation of crustacean allergy sera with the recombinant shrimp tropomyosin Met e I also removed their IgE reactivity to lobster muscle extracts. The results suggest that patients with allergic reactions to crustaceans have common and possibly cross-reactive IgE-reactive epitopes in lobster and shrimp.
The growing demand for seafood and the subsequent increasing risk of seafood allergy in the population at large make it important to elucidate the molecular basis of seafood allergy and identify the seafood allergens at the molecular level. The clinical symptoms, physiological mechanisms, current findings of the immunological and molecular basis of shellfish allergy as well as future directions for the prevention of shellfish allergy. Interestingly, identified seafood allergens belong to a group of muscle proteins, namely the parvalbumins in codfish and tropomyosin in crustaceans. In addition, there is strong immunological evidence that tropomyosin is a cross-reactive allergen among crustaceans and mollusks. The molecular cloning, expression and biochemical characterization of seafood allergens will continue to provide valuable tools in the further understanding of the mechanisms of seafood allergy as well as the future development of immunomodulation regimen.
Fish allergy represents 18 % of all cases of food allergy in children while reactions caused by crustacea and mollusks account for 3.8 % and 1.6 % respectively. Cross-reactivity is defined as the recognition of distinct antigens by the same IgE antibody, demonstrable by in vivo and in vitro tests, which clinically manifests as reactions caused by antigens homologous to different species.
Subclinical sensitization can also occur, giving rise to patients sensitized to particular fish or shellfish but who do not present symptoms on consumption.Cod and shrimp have been the models used to study allergy to fish and crustacea respectively. The major allergens responsible for cross-reactivity among distinct species of fish and amphibians are proteins that control calcium flow in the muscular sarcoplasm of these animals, called parvalbumins, with a molecular weight of approximately 12 kD and an isoelectric point of 4.75, resistant to the action of heat and enzymatic digestion. Recently, recombinant carp parvalbumin has been reproduced, confirming that this allergen contains 70 % of the IgE epitopes present in natural extract of cod, tuna and salmon, which makes it a valid tool in the diagnosis of patients with fish allergy. Moreover, this recombinant allergen could constitute the basis for the development of immunotherapy against food allergy. In the case of shellfish, a non-taxonomic group that includes crustacea and mollusks, the major allergen is tropomyosin, an essential protein in muscle contraction both in invertebrates and vertebrates.
In invertebrates, tropomyosins, which have a molecular weight of between 38 and 41 kD, show great homology in their amino acid sequence and are the panallergens responsible for cross-reactions between crustacea, insects, mites, nematodes, and different classes of mollusks. It is estimated that 50 % of individuals allergic to some type of fish are at risk for reacting to a second species, while those allergic to some type of crustacea present a risk of 75 % due to the greater similarity among tropomyosins than among parvalbumins. In addition, up to 40 % of patients sensitized to one or more fish do not present symptoms on consuming other species, the best tolerated of which belong to the Scombroidea family which includes tuna.
Shrimp is known to be the most common causative agent in seafood allergy. Patients with shrimp allergy often exhibit allergic symptoms to a variety of seafoods such as crabs and clams. Patient with shrimp allergy who developed oral swelling and pain accompanied with an uncomfortable feeling after ingestion of scallops followed by intensive exercise. Laboratory investigation showed that serum immunoglobulin (Ig)E molecules reacting with several kinds of crustaceans and mollusks, including shrimp, crab and scallops. Immunoblotting revealed that her serum IgE reacted with the 38 kDa bands for shrimp, crab and scallops, suggesting that tropomyosin was the major allergen. Dot-blot inhibition analysis showed a cross-reactivity among shrimp, crab and scallops. The cross-reactivity of IgE in this patient resulted from the high homology of tropomyosins.
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