Fish allergy
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Fish allergy Presented by Rapisa Nantanee, M.D. August23, 2019
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Fish allergy
- 1. Fish Allergy Topic Review 23rd August 2019 Rapisa Nantanee, M.D. Pediatric Allergy and Immunology Unit King Chulalongkorn Memorial Hospital This Photo by Unknown Author is licensed under CC BY-SA
- 2. Seafood refers to several distinct groups of edible aquatic animals including fish, crustacean, and mollusc. Molecular Immunology. 100 (2018) 28–57.
- 3. Outline • Epidemiology of Fish Allergy • Classification of Fish • Fish Allergens • Diagnosis of Fish Allergy • Cross Reactivity • Treatment
- 4. Epidemiology
- 5. Assessed using clinical history and sensitization • In Europe • The highest prevalence was seen in Norway, where 1.1% (95% CI, 0.4% - 3.1%) of 2-year-olds were sensitized to fish, and the lowest was 0% (95% CI, 0% - 0.1%) of 0- to 2-year-olds in Israel. • Adult fish allergy prevalence ranged from 0.8% (95% CI, 0.2% - 2.5%) in 20- to 44-year-olds in Germany to 0% in several other studies. • In Southeast Asia • The prevalence was 0.2% (95% CI, 0% - 1.0%) of 6-month to 6-year-olds in Thailand. Ann Allergy Asthma Immunol. 117 (2016) 264-272.
- 6. Assessed using food challenges • In Europe • Open food challenges • Only 1 study in Denmark reported data for adult fish (cod) allergy as 0.1% (95% CI, 0% - 0.8%) of 22-year-olds. • For children, the lowest confirmed prevalence was 0% (95% CI, 0% - 4.2%) of those younger than 3 years old in Denmark, and the highest was 0.1% (95% CI, 0% - 0.8%) of 6-year-olds in Finland. • Double-blind, placebo-controlled food challenge • The rate of confirmed prevalence ranged from 0.2% (95% CI. 0% - 0.9%) in Denmark to 0% (95% CI, 0e0.1%) in Turkey in adults. • From 0.3% (95% CI, 0% - 2.0%) in Iceland to 0% in Denmark, Turkey, and the United Kingdom in children. • In Southeast Asia • A prevalence of 0.2% (95% CI, 0% - 1.4%) was found for 3- to 7-year-olds based on an open food challenge. Ann Allergy Asthma Immunol. 117 (2016) 264-272.
- 8. Molecular Immunology. 100 (2018) 28–57.
- 9. Molecular Immunology. 100 (2018) 28–57.
- 10. Tetrapoda • Contains all the four-limbed vertebrates including • Amphibians • Birds • Mammals • Reptiles Molecular Immunology. 100 (2018) 28–57. Pictures from www.amphibianfact.com, theconversation.com, en.wikipedia.org
- 11. Ray-finned fish (Actinopterygii) • The largest subclass and includes all edible bony fish. Molecular Immunology. 100 (2018) 28–57. Pictures from seafoodhomedelivery.com.au, puparn.rid.go.th, th.wikipedia.org,
- 12. Lobe-finned fish (Sarcopterygii) • Most Sarcopterygii species are extinct. • The coelacanths being the oldest discovered order - having a continuous presence for 100 million years. Molecular Immunology. 100 (2018) 28–57. Pictures from steemit.com/science/@mountainwashere, ourmarinespecies.com
- 13. Bony fish (Osteichthyes) • The largest group of all vertebrates consisting of 45 orders and over 435 families. • Endoskeleton made of stable cranial bones • Reproduce mostly externally • Found in fresh and marine water Molecular Immunology. 100 (2018) 28–57.
- 14. Cartilaginous fish (Chondrichthyes) • Endoskeleton made of cartilage • Reproduce internally • Found primarily in marine water Molecular Immunology. 100 (2018) 28–57.
- 15. Elasmobranchii • Consist of • Sharks (Selachii) • Rays • Skates (Batoidea) • Sawfish Molecular Immunology. 100 (2018) 28–57. Pictures from www.stuff.co.nz, en.wikipedia.org
- 16. Ghost sharks (Holocephali) • Only one surviving order (Chimaeriformes) • Consists of • Rat fish • Rabbit fish • Elephant fish Molecular Immunology. 100 (2018) 28–57. Pictures from www.finsunited.co.nz, en.wikipedia.org, www.afma.gov.au
- 17. Fish Allergens
- 18. Fish Allergens • Fish allergens have been identified in various parts of the fish, including fish muscle, skin, bones, roe, milt (seminal fluid) and blood. • Parvalbumin, aldolase A, β-enolase, tropomyosin and vitellogenin Molecular Immunology. 100 (2018) 28–57.
- 19. Journal of Asthma and Allergy 2018:11 Atlantic herring Common carp Cod Atlantic cod Asian sea bass Whiff Rainbow trout Indian mackerel ปลาลัง Atlantic salmon Pacific sardine Redfish Yellowfin tuna Swordfish Mozambique tilapia ปลาหมอเทศ Chum salmon
- 20. Parvalbumin • Parvalbumin was first identified as the major fish allergen in 1969. • 10–12 kDa protein • Abundant in muscle • Physiologically important for calcium binding • Thermally stable • Maintains its allergenic activity and antigenicity even under acidic conditions and after pepsinolysis • White muscles have a higher parvalbumin content than the dark muscles. - - Fish with more dark muscles such as tuna and mackerel is less allergenic than fish with more white muscle such as cod and haddock. • Fish contain mainly beta-subtype parvalbumins (allergenic). Journal of Asthma and Allergy 2018:11
- 21. Parvalbumin • β-parvalbumins are predominantly expressed in bony fish and are known to cause IgE-mediated allergic reactions in humans. • In cartilaginous fish, only α-parvalbumins have been found, for which a lower IgE-reactivity is proposed. Molecular Immunology. 100 (2018) 28–57.
- 22. Aldolase A and β-enolase • Aldolase A (40 kDa) and β-enolase (47–50 kDa), are essential glycolytic enzymes. • Important allergens in muscle tissue of bream, cod, salmon and tuna • Sensitive to heat treatment • Less resistant to food processing than parvalbumin Molecular Immunology. 100 (2018) 28–57.
- 23. Tropomyosin • Structural protein (33–39 kDa) • A pan-allergen for shellfish, has been registered as an allergen for only one fish species by WHO/IUIS, Mozambique tilapia (Oreochromis mossambicus, WHO/IUIS Ore m 4). • A more recent study from 2018 has further highlighted the importance of recognising fish tropomyosin as an allergen by demonstrating IgE-reactivity to cod and albacore tropomyosin in 10/19 patients. Molecular Immunology. 100 (2018) 28–57.
- 24. Other fish allergens • Collagen was first described as a fish allergen in 2001 • A study by Hamada et al, where it was purified from muscle tissue of tuna and demonstrated IgE binding in 5/8 patients´ sera. • In another study by Kobayashi et al, IgE reactivity to collagen from Pacific mackerel skin was shown in 18/36 patients (50%) with confirmed allergy to fish by specific IgE ELISA. • Vitellogenin as the major allergen in fish roe (caviar) • Protamine as the major allergen in milt (seminal fluid) • Serum albumin as a potential allergen in blood • Some of these proteins are also expressed in muscles or present in muscle tissue due to contamination. Molecular Immunology. 100 (2018) 28–57.
- 25. Diagnosis
- 26. Clinical assessment • Information is collected on allergic episodes • Type and quantity of suspected seafood ingested • Time to onset of symptoms • Single or multiple symptoms usually appear immediately or within two hours following exposure. • Late phase reactions of up to eight hours after ingestion have been reported. • Whether previous exposure to suspected culprits elicited similar allergic responses • When the last reaction to food occurred • Whether exercise was performed before an allergic episode • Family history of food allergy is often considered - the link between genetics and seafood allergy has not been thoroughly established. Journal of Asthma and Allergy 2018:11 Molecular Immunology. 100 (2018) 28–57.
- 27. Clinic Rev Allerg Immunol (2014) 46:258–271.
- 28. Skin Prick Test • The cross-linking of specific IgE with allergens introduced into the skin triggers an immunologic milieu, leading to the release of various mediators including histamine, which is responsible for localized swelling around the prick area. • Commercially available fish and shellfish extracts are limited compared to the wide variety of dietary fish and shellfish. • Positive predictive value often below 50 %. • Prick-to-prick tests using fresh food. • Not very specific with a positive predictive value often below 50 % Journal of Asthma and Allergy 2018:11 Clinic Rev Allerg Immunol (2014) 46:258–271
- 30. Specific IgE measurement • Useful for diagnosis, predicting the development of tolerance and persistence of seafood allergy, and monitoring allergy treatments Journal of Asthma and Allergy 2018:11
- 31. Journal of Asthma and Allergy 2018:11
- 32. J Allergy Clin Immunol. May 2001.
- 33. Adverse Reactions to Seafood Immunological IgE-mediated IgE test and/or SPT Positive Decision point for IgE test and/or SPT IgE level above decision point Diet restriction IgE level below decision point Negative Oral food challenge Positive Diet restriction Negative No diet restriction Non-IgE mediated - FPIES - Others Non-immunological - Food poisoning DBPCFC and overnight observation for suspected food poisoning Seafood toxin analysis for suspected poisoning Adapted from Journal of Asthma and Allergy 2018:11, Molecular Immunology. 100 (2018) 28–57
- 34. Adverse clinical reactions resembling seafood allergy Scombroid poisoning (histamine poisoning) • An allergy-like reaction • Occurs after eating fish that have been improperly refrigerated after capture Marine algae toxins • A major cause of adverse seafood reactions • “Red tides” Paralytic shellfish poisoning toxins • Minute dinoflagellates produce over 20 related chemical compounds, including neurotoxin saxitoxin, which blocks the neuronal and muscular sodium channels. Diarrhetic shellfish poisoning toxins • Produced by algae • Symptoms are mainly gastrointestinal problems such as diarrhea, nausea, vomiting, and abdominal pain. Molecular Immunology. 100 (2018) 28–57.
- 35. Adverse clinical reactions resembling seafood allergy Ciguatera poisoning • Eating fish that has been contaminated by algae-derived toxins • Symptoms manifest mainly by gastrointestinal (diarrhea, vomiting), neurologic (temperature reversal, blurred vision) and cardiovascular (drop in blood pressure, heart block) signs. Bacterial and viral contamination • Different vibrio strains such as V. cholerae or V. vulnificus, Listeria and Salmonella species • Consumption of raw shellfish, including oysters, often involves small round- structured viruses (SRSVs) and Norwalk virus. • Symptoms can occur several hours after consumption and include gastrointestinal symptoms. Anisakis parasite allergy • This nematode parasite infects many marine fish species. • Cooking of fish at temperatures above 60 °C or storage in industrial freezers for two days is required to kill the parasite. • cause two major problems in humans: • 1) Anisakis infection (anisakiasis) • 2) Anisakis allergy Seafood intolerance • May be caused by pharmacological properties of the ingested seafood • Severe headaches • Vasoactive amines such as histamine and tyramine, often found in large quantities in canned and pickled fish, and fish autolysates, also fresh fish such as herring, tuna, and mackerel • Food dyes (e.g. tartrazine) and food additives (e.g. monosodium glutamate, MSG) Molecular Immunology. 100 (2018) 28–57.
- 36. Component-resolved diagnosis Journal of Asthma and Allergy 2018:11
- 37. Component-resolved diagnosis • Aims at measuring IgE antibodies to individual allergenic components in the form of proteins or peptides to provide more details on the sensitizing profile of patients • Studies on the diagnostic utility of CRD in fish and shellfish allergies are lacking. Journal of Asthma and Allergy 2018:11
- 38. Molecular Immunology. 100 (2018) 28–57.
- 39. Cross Reactivity
- 40. Cross Reactivity: Fish Allergens • Most fish express several different isoforms of the major fish allergen parvalbumin (up to 5), primarily of the β-lineage, with a large molecular diversity most likely being responsible for differential clinical reactivity resulting in mono- or multiple-sensitivity. • Approximately 50% chance of being cross-reactive to another fish species • Non-fish parvalbumins are WHO/IUIS-recognized allergens from frog (α- and β-isoform) and chicken (α-isoform) with reported cross- reactivity between chicken and fish parvalbumins. Molecular Immunology. 100 (2018) 28–57.
- 41. Molecular Immunology. 100 (2018) 28–57.
- 42. Molecular Immunology. 100 (2018) 28–57.
- 43. EAACI Molecular Allergology User´s Guide 2016
- 44. Cross Reactivity: Fish Allergens • Non-fish parvalbumins are WHO/IUIS-recognized allergens from frog (α- and β-isoform) and chicken (α-isoform) with reported cross- reactivity between chicken and fish parvalbumins. • Large amino acid sequence diversity between species such as cod, carp, and salmon. • The vast majority of the more than 32,300 fish species have never been investigated for their allergens. • The allergenicity of any given fish species is dependent on two factors; the allergenicity of the proteins (in this case parvalbumin), and on the amount of the allergens present in the tissue. Molecular Immunology. 100 (2018) 28–57.
- 45. Cross-reactivity between fish, crustacean, and mollusc • Several allergens found independently in fish, crustacean or mollusc species originate from the same protein family or share a similar structure and function. • This may be a potential cause for cross-reactivity between vertebrate and invertebrate species. • Allergenicity and IgE recognition of tropomyosin has been well documented in crustacean, mollusc and fish (tilapia). A 2018 study reported the potential cross-reactivity of tropomyosin between shellfish and fish. • Need for further investigations Molecular Immunology. 100 (2018) 28–57.
- 46. Treatment
- 47. Therapeutic development for seafood allergy • Current treatment strategies for seafood allergy are complete avoidance of the offending source. • The major challenge in the development of seafood immunotherapy, using either whole extracts or natural purified allergens, is the risk of severe allergic reactions. • Alternative treatments of seafood allergy include the use of probiotics and Chinese herbal medicines. Molecular Immunology. 100 (2018) 28–57.
- 48. Vaccine candidates, hypoallergenic derivatives and clinical trials for fish allergy • The most developed immunotherapy for fish allergy is the use of hypoallergenic proteins for antibody binding to mimic their natural counterparts. • To raise IgG to block the subsequently introduced parvalbumin from binding to IgE • The first-in-man • Subcutaneous immunotherapy showed a promising outcome and hence Phase I/IIa clinical trials were conducted with 15 participants in Denmark, 2013 (NCT number: NCT02017626), followed by Phase Iib clinical trial with 45 participants across six countries in 2015 (NCT number: NCT02382718). Molecular Immunology. 100 (2018) 28–57.
- 49. Thank You for Your Attention
Editor's Notes
- Other seafood, such as jellyfish (phylum Cnidaria), can trigger anaphylaxis upon ingestion (Imamura et al., 2013), but was reported to be safe for patients with allergy to the seafood groups mentioned above (Amaral et al., 2018).
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- ปลาสเกต ปลาฉนาก
- For consumption, and therefore allergy research, bony fish are the most relevant. Only in a few studies has the allergenicity of cartilaginous fish been investigated, and these suggest lower allergenicity compared to bony fish (Stephen et al., 2017).
- 21 allergens from 15 fish species are officially recognized by the World Health Organization/International Union of Immunological Societies at present Oncorhynchus keta Pacific salmon/ chum salmon
- The most commonly characterised allergenic fish parvalbumins from cod, salmon and carp were demonstrated to be responsible for 70–100% of allergic reactions to fish and fish products
- Aldolase was first identified as a fish allergen in Pacific salmon in 2009 (Nakamura et al., 2009). Enolase was detected as a fish allergen in bream in 2011 by Liu et al., where IgE binding to this protein was demonstrated in 10 individuals with confirmed bream allergy by immunoblotting.
- Albacore = longfin tuna
- As shellfish is recognized as one of the major food groups to induce food-dependent exercise-induced anaphylaxis only one report of an estimated heritability of 0.54 in a twin study on shellfish allergy.
- The major route of sensitization to fish is however through the gastrointestinal tract. In addition to uptake via the gastrointestinal tract, reactions to inhaled proteins are an important aspect of fish allergy in both the domestic and occupational environment. In domestic settings, a Spanish study reported 11 % of children from a group of 197 allergic children experienced repeated allergic reactions upon incidental inhalation of fish odors or vapors, even while on strict fish avoidance. In most cases, these episodes occurred at home when other people were eating fish In the workplace environment, occupational allergy, and asthma is reported among worker processing a variety of fish species including trout, salmon, pilchard, anchovy, plaice, hake, tuna, haddock, cod, and pollock Atopy, smoking, and level of exposure are significant risk factors for allergic sensitization and the development of occupational asthma. Fish antigen exposure levels of more than 30 ng/m3 have shown significant correlation with sensitization and work-related asthma symptoms A similar study quantified raw fish allergens from an open-air fish market and detected allergen concentrations ranging from 2 to 25 ng/m3, very similar to the levels identified in the occupational setting causing allergic sensitization From data on allergen exposure available so far, it can be expected that extended exposure to aerosolized fish allergens can generate sensitization also in the domestic environment and probably also in children
- Scombroid poisoning: Bacteria in the tissue and on the fish skin convert the amino acid histidine into histamine, one of the major mediators of allergic reactions. Enterobacteriaceae, such as Proteus morganii and Klebsiella pneumonia, are often implicated. Fish with a high content of red meat, which turns brown upon cooking is commonly involved including mackerel, tuna, herring, sardines, marlin, anchovies and bluefish. Affected fish often have a metallic or peppery taste. paralytic shellfish poisoning toxins: Symptoms include gastrointestinal signs (nausea, vomiting, diarrhea), but may include a prickly sensation in the fingertips and toes and even muscular paralysis. Ciguatera poisoning causes more human illnesses than any other seafood toxicity and affects up to 50,000 individuals annually cause two major problems in humans: 1) Anisakis infection (anisakiasis) Infection may cause nausea, vomiting, stomach pain, and sometimes appendicitis, bowel blockage or bleeding. Diagnosis usually requires an endoscopy. However, our immune system destroys the parasite after about three weeks. 2) Anisakis allergy the allergic reaction is directed towards allergenic proteins of this fish parasite, not to the fish itself. The allergens of Anisakis simplex appear to be not destroyed by heat or cooking and so allergic reactions may be triggered by dead parasites, even if the fish has been long frozen or well cooked. The presence of Anisakis specific IgE antibody can confirm allergic sensitization.
- Scombroid poisoning: Bacteria in the tissue and on the fish skin convert the amino acid histidine into histamine, one of the major mediators of allergic reactions. Enterobacteriaceae, such as Proteus morganii and Klebsiella pneumonia, are often implicated. Fish with a high content of red meat, which turns brown upon cooking is commonly involved including mackerel, tuna, herring, sardines, marlin, anchovies and bluefish. Affected fish often have a metallic or peppery taste. paralytic shellfish poisoning toxins: Symptoms include gastrointestinal signs (nausea, vomiting, diarrhea), but may include a prickly sensation in the fingertips and toes and even muscular paralysis. Ciguatera poisoning causes more human illnesses than any other seafood toxicity and affects up to 50,000 individuals annually cause two major problems in humans: 1) Anisakis infection (anisakiasis) Infection may cause nausea, vomiting, stomach pain, and sometimes appendicitis, bowel blockage or bleeding. Diagnosis usually requires an endoscopy. However, our immune system destroys the parasite after about three weeks. 2) Anisakis allergy the allergic reaction is directed towards allergenic proteins of this fish parasite, not to the fish itself. The allergens of Anisakis simplex appear to be not destroyed by heat or cooking and so allergic reactions may be triggered by dead parasites, even if the fish has been long frozen or well cooked. The presence of Anisakis specific IgE antibody can confirm allergic sensitization.
- β-parvalbumins from 13 fish species were officially registered by WHO/IUIS and named accordingly
- - Parvalbumin isoforms from the same species often share less than 68% amino acid sequence identity as shown for barramundi and rainbow trout, adding complexity to the detection of allergenic parvalbumins. - Among all β-parvalbumins, the sequence identities range from 46 to 99%, with the lowest identity between the respective isoforms from Baltic cod and rainbow trout, suggesting the possibility of limited cross-reactivity. - Human α-parvalbumin (UniProt: P20472) has a sequence identity with all WHO/IUIS-registered α- and β-parvalbumins of 44-58% and 68-79%, respectively.
- Serologic cross-reactions have been described between fish and frog beta-parvalbumins. Cross-reactivity among fish and chicken allergens including parvalbumins, enolases, and aldolases have been reported, and described as “fish-chicken syndrome” phenomenon. Demonstrated that the parvalbumin content may differ up to 48 fold between fish species (0.2–11.2 mg of parvalbumin per gram of tissue), dependant on the size of the specimen, the species and also the type of fish (sedentary or migratory type). The parvalbumin content within one species can differ up to 7.4-fold between different muscle parts, as demonstrated for the Mediterranean flying fish. Generally, higher parvalbumin content is observed in dorsal and rostral compared to ventral and caudal parts of fish muscle, respectively. Parvalbumin is more abundant in white compared to dark tissue. All other fish allergens have only been investigated in a limited number of species and their cross-reactivity is poorly understood.
- Tilapia ปลานิล
- Recombinant fish parvalbumins have been expressed to explore potential use in immunotherapy (Swoboda et al., 2007) and treatment (Freidl et al., 2017) of fish allergy.