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Allergen Encyclopedia
Table of Contents

Whole Allergen

f205 Herring

f205 Herring Scientific Information

Type:

Whole Allergen

Display Name:

Herring

Route of Exposure:

Ingestion

Family:

Clupeidae

Species:

Clupea harengus

Latin Name:

Clupea harengus

Other Names:

Baltic herring, Atlantic herring

Summary

Herring (Clupea harengus L.) has been a valuable commercial fish since the medieval period and is usually consumed in various processed forms like salted, marinated, smoked, and canned due to its high amounts of vitamin D, long-chain polyunsaturated fatty acids, and calcium. It is prevalently found in the Northeast and Northwest Atlantic. Furthermore, the Baltic Sea, North Sea, and the coastal waters of Canada, Britain, Iceland, Norway are the prime fishing grounds for herring. The prevalence of fish allergy is found to be higher in countries with high fish consumption and fish-processing industries. Herring allergy is primarily induced through the oral route and secondarily through exposure to vapors (while processing the fish) and through skin contact. Therefore, consumption of herring by sensitized individuals may trigger oral symptoms, respiratory symptoms (asthma, frequent sneezing, dyspnea, irritable running nose), and allergic contact dermatitis. In herring, Clu h 1 (Beta-parvalbumin), a 12 kDa calcium-binding and heat-resistant protein, is the major allergen found in the fish muscle. Herring has been reported to possess cross-reactivity with Anchovy, Sardine, Pacific herring. Furthermore, herring parvalbumin is also cross-reactive with parvalbumins from salmon (Sal s 1), pollock (The c 1), wolfish, Baltic cod (Gad c 1), and Atlantic cod (Gad m 1).

Allergen

Nature

Herring (Clupea harengus L.) has been reported to be a valuable commercial fish since the medieval period (1). The upper part of the body of herring is dark bluish-green (or steel blue) with blackish-blue stout, while the sides and belly are silver in color. The lower jaw extends slightly beyond the upper jaw. The gill covers of this fish are smooth, with slightly blunt keel scales along the belly's edge. Moreover, it possesses thin, large, loosely attached scales on the body and an invisible lateral line. The mouth of herring is usually large, along with small weak teeth and absence of barbel. Herring can grow up to a size (length) of around 23 to 36 cm. The female herring lays around 20,000-40,000 eggs on the seabed, typically in water with a depth of 10-80 m. The eggs are naturally sticky and are laid on hard ground covered with small stones, shells, or seaweed, where they attach themselves (2).

Herring has been reported to possess high amounts of vitamin D, long-chain polyunsaturated fatty acids, and calcium (3). This fish is usually consumed in various processed forms like salted, marinated, smoked, and canned. Additionally, herring is also used in the manufacturing of animal food (like canned pet food) (2).

Taxonomy

Out of a huge variety of fish species, it has been found that only a small number of orders of fish belonging to the class Actinopterygii (ray-finned fish) are consumed, which includes Clupeiformes, Gadiformes, Salmoniformes, Pleuronectiformes, Cypriniformes, and Perciformes (4).

Taxonomic tree of Herring (5, 6)
Domain Eukaryota
Kingdom Metazoa
Phylum Chordata
Subphylum Vertebtata
Class Actinopterygii
Order Clupeiformes
Family Clupeidae
Genus Clupea
Species Clupea harengus

Tissue

Parvalbumin, a major fish allergenic protein, is a small, heat-resistant, water-soluble, calcium-binding protein present in the fish muscle. In herring, Beta-parvalbumin (Clu h 1), a 12 kDa protein, has been reported to be present in the fish muscle (7). 

Epidemiology

Worldwide distribution

Seafood allergy (fish and shellfish) is regarded as one of the most common causes of allergy in coastal areas. Moreover, this allergy has been reported to be prevalent in eastern countries like Singapore and Japan (8).

The prevalence of fish allergy is found to be higher in countries with high fish consumption and fish-processing industries (9). In Asia, the Philippines has been reported to have the highest prevalence (2.29%) of fish allergy compared to Singapore (0.26%) and Thailand (0.29%) (10, 11).

Furthermore, in European countries, the prevalence of fish allergy in the adult population was found to be about 0.8% and is a little higher than the children. The countrywide prevalence of clinically confirmed fish allergy in the pediatric population in Europe was found to be 0.7 % in Sweden (4 years old), 0.6% in Germany (2-6 years old), and 5% in Finland (1-4 years old) (12). In Norway, fish hypersensitivity is frequently reported due to occupational exposure in the fish industry and its extensive consumption. Furthermore, fish allergy has been found to be affecting around 0.1% of the country's population (13).

A US-based cross-sectional survey reported seafood allergy in 2.3% of the general population, of which 2% was for shellfish, 0.4% for fish, and 0.2% for both fish and shellfish (14).

According to a Denmark-based study conducted among fish-factory workers, the prevalence of herring allergy was reported to be around 13% (15).

A population study conducted in Germany confirmed 0.5% as the prevalence of herring allergy among the adult population (16).

Risk factors

Parvalbumin, a major allergenic protein in fish, is found to be highly heat-resistant. Therefore, processing the fish might not be helpful in decreasing the parvalbumin-mediated allergenicity (17).

Furthermore, fish parvalbumin-sensitized patients with antacid medication are claimed to be at an increased risk of developing severe reactions compared to others (18).

Additionally, around 50% of individuals allergic to certain fish are also found to be at risk of reacting to other fish species (19).

Environmental Characteristics

Living environment

Herrings usually spend the first few years of their life in coastal nurseries. Later they migrate offshore into the deeper water levels and eventually club with the adult population and get involved in the feeding and spawning migrations (20). 

Worldwide distribution

Atlantic herring is prevalently found in Northeast and Northwest Atlantic (2, 20). In the northeast Atlantic, it is found from the Bay of Biscay in the south to Spitzbergen and Novaya Zemlya in the north. Moreover, in the northwest Atlantic, it spreads from the coast of Maine northwards. The Baltic Sea, North Sea, and the coastal waters of Canada, Britain, Iceland, Norway are regarded as the prime fishing grounds for herring (2). Furthermore, in Sweden, herring is a frequently caught fish, followed by salmon and cod (21). Moreover, Atlantic herring has been reported as one of the most frequently used fish species in fish food products in the retail market of Central Europe (19).

Route of Exposure

Main

Ingestion of fish is considered the route of exposure that may cause IgE-mediated hypersensitivity (4, 13).

Moreover, inhalation of fish allergens is found to be one of the routes of exposure (occurs during outdoor drying, fish odors, and fumes produced during cooking). Furthermore, direct skin contact with the fish has also been reported as a route of exposure that can occur while cooking or processing the fish (4, 13).

Clinical Relevance

Fish allergy has been observed commonly among children and young adults and may be associated with symptoms like oral allergy syndrome, asthma, and allergic contact dermatitis (4, 13).

Oral symptoms

According to a study, 79% (15/19) of the fish-allergic patients were found to exhibit allergic symptoms after the consumption of herring (22).

Furthermore, another study confirmed the presence of IgE antibodies to herring among fish-allergic adults. Moreover, the study also reported clinical sensitivity (0.93) and specificity (0.87) towards herring (23). 

Respiratory symptoms

According to a study, asthma was reported among 21% (4/19) fish-factory workers. Furthermore, the study also confirmed around 32% (6/19) of the fish-factory workers possess work-related respiratory symptoms (15).

Dyspnea (6.1%), frequent sneezing (9.1%), and irritable, running nose (18.2%) was reported by a study conducted among production workers (n=11) working in herring plant (24).

Atopic dermatitis

A study reported the presence of IgE antibodies to herring in patients with atopic dermatitis (25).

Moreover, a case study also found specific anti-herring IgE antibodies in the serum of a patient with occupational protein contact dermatitis (26).

Diagnostics Sensitization

Parvalbumin can be extensively utilized to diagnose and manage fish allergy through parvalbumin-specific IgE testing (8).

Prevention and Therapy

Prevention strategies

Avoidance

Complete avoidance of fish and fish-based food products from the diet can be considered as preventive measures for fish allergy. In addition, to avoid accidental consumption, individuals allergic to fish are usually advised to cross-check the packaged food labels extensively before consuming any retail food products (4, 19, 27, 28).

Molecular Aspects

Allergenic molecules                  

According to WHO/IUIS, Clu h 1 has been identified, listed as an allergenic molecule from herring (Clupea harengus), and is represented in the table below (29).

Allergen

Biochemical name

Molecular weight

Clu h 1

Beta-parvalbumin

 12 kDa

According to a study, the highest parvalbumin level (4.75 mg/g muscle, based on quantitative ELISA test) was observed in herring compared to other fish species (cod, tuna, carp, salmon/trout, mackerel, redfish) (7). However, parvalbumin content in fish muscle has been reported to be extremely variable depending on the fish species (27).

A study reported that proteins extracted from raw wolf herring muscle with molecular weights of 12, 24, 38, and 51 kDa exhibited significant IgE-reactivity with sera of patients with fish allergy. Moreover, 88% (8/9) of the patient's sera showed reactivity to the 12 kDa and 51 kDa proteins (via Western blotting) (8).

Cross-reactivity

Herring is found to exhibit cross-reactivity with other fishes from the Clupeiformes order (like Anchovy and Sardine) (13). A strong cross-reactivity has also been reported between Atlantic herring and Pacific herring (19).

Furthermore, herring have been found to be highly cross-reactive (parvalbumin-based) with other fish species like Salmon, Wolfish, Baltic cod, Pollock, and Atlantic cod (13, 18).

Compiled By

Author: Turacoz Healthcare Pvt. Ltd

Reviewer: Dr. Christian  Fischer

 

Last reviewed:February 2022

References
  1. Hammer C, von Dorrien C, Zimmermann C, Stepputtis D, Stuermer I, Kotterba P, et al. A Review on Herring, Clupea Harengus (Actinopterygii: Clupeiformes: Clupeidae) Recruitment and Early Life Stage Ecology in the Western Baltic Sea. Acta Ichthyologica Et Piscatoria. 2013;43:169-82.
  2. Stroud GD. The Herring. MINISTRY OF AGRICULTURE, FISHERIES AND FOODTORRY RESEARCH STATION. FAO. 2001. Available from: https://www.fao.org/3/x5933e/x5933e01.htm#Introduction.
  3. Lindqvist H, Langkilde AM, Undeland I, Rådendal T, Sandberg AS. Herring (Clupea harengus) supplemented diet influences risk factors for CVD in overweight subjects. European Journal of Clinical Nutrition. 2007;61(9):1106-13.
  4. Lee PW, Nordlee JA, Koppelman SJ, Baumert JL, Taylor SL. Evaluation and comparison of the species-specificity of 3 antiparvalbumin IgG antibodies. J Agric Food Chem. 2011;59(23):12309-16.
  5. CABI. Clupea harengus (Atlantic herring) 2021 [18.08.2021]. Available from: https://www.cabi.org/isc/datasheet/88782.
  6. NCBI. Clupea harengus 2021. Available from: https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=7950.
  7. Kuehn A, Scheuermann T, Hilger C, Hentges F. Important variations in parvalbumin content in common fish species: a factor possibly contributing to variable allergenicity. Int Arch Allergy Immunol. 2010;153(4):359-66.
  8. Mohammadi M, Falak R, Mokhtarian K, Khoramizadeh MR, Sadroddiny E, Kardar GA. Identification and Characterization of Main Allergic Proteins in Cooked Wolf Herring Fish. Iran J Allergy Asthma Immunol. 2016;15(5):363-71.
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  10. Tong WS, Yuen AW, Wai CY, Leung NY, Chu KH, Leung PS. Diagnosis of fish and shellfish allergies. J Asthma Allergy. 2018;11:247-60.
  11. Connett GJ, Gerez I, Cabrera-Morales EA, Yuenyongviwat A, Ngamphaiboon J, Chatchatee P, et al. A population-based study of fish allergy in the Philippines, Singapore and Thailand. Int Arch Allergy Immunol. 2012;159(4):384-90.
  12. Ruethers T, Taki AC, Johnston EB, Nugraha R, Le TTK, Kalic T, et al. Seafood allergy: A comprehensive review of fish and shellfish allergens. Mol Immunol. 2018;100:28-57.
  13. Van Do T, Elsayed S, Florvaag E, Hordvik I, Endresen C. Allergy to fish parvalbumins: studies on the cross-reactivity of allergens from 9 commonly consumed fish. J Allergy Clin Immunol. 2005;116(6):1314-20.
  14. Sicherer SH, Munoz-Furlong A, Sampson HA. Prevalence of seafood allergy in the United States determined by a random telephone survey. J Allergy Clin Immunol. 2004;114(1):159-65.
  15. Bønløkke JH, Thomassen M, Viskum S, Omland Ø, Bonefeld-Jørgensen E, Sigsgaard T. Respiratory symptoms and ex vivo cytokine release are associated in workers processing herring. International Archives of Occupational and Environmental Health. 2004;77(2):136-41.
  16. Zuberbier T, Edenharter G, Worm M, Ehlers I, Reimann S, Hantke T, et al. Prevalence of adverse reactions to food in Germany - a population study. Allergy. 2004;59(3):338-45.
  17. Poulsen LK MM, Kuehn A. Allergy to fish. EAACI Molecular Allergology User's Guide Part B Using Molecular Allergology in the Clinical Practice Chapter B12. 2016:173-80.
  18. Kuehn A PL, Morisset M. Parvalbumins. EAACI Molecular Allergology User's Guide Part C Cross-Reactive Molecules & Their Clinical Relevance Chapter C08. 2016:353-62.
  19. Rencova E, Kostelnikova D, Tremlova B. Detection of allergenic parvalbumin of Atlantic and Pacific herrings in fish products by PCR. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2013;30(10):1679-83.
  20. ICESCIEM. Herring. ICES-Fish map 2006. Available from: https://www.ices.dk/about-ICES/projects/EU-RFP/EU%20Repository/ICES%20FIshMap/ICES%20FishMap%20species%20factsheet-herring.pdf.
  21. Dahlman-Höglund A, Renström A, Acevedo F, Andersson E. Exposure to parvalbumin allergen and aerosols among herring processing workers. Ann Occup Hyg. 2013;57(8):1020-9.
  22. Schulkes KJ, Klemans RJ, Knigge L, de Bruin-Weller M, Bruijnzeel-Koomen CA, Marknell deWitt A, et al. Specific IgE to fish extracts does not predict allergy to specific species within an adult fish allergic population. Clin Transl Allergy. 2014;4:27.
  23. Hansen TA, L; Bindslev-Jensen, C; Poulsen, LK. . Results of the CAP System and Immunoblotting in clinically fish allergic adults. . Allergologie 1995;18:407. 1995.
  24. Bang B, Aasmoe L, Aamodt BH, Aardal L, Andorsen GS, Bolle R, et al. Exposure and airway effects of seafood industry workers in northern Norway. J Occup Environ Med. 2005;47(5):482-92.
  25. Lindqvist AI, Z.; Tanaka, A; Yman, L. Seafood specific IgE in atopic dermatitis. Ann Allergy 1993;70:58. 1993.
  26. Alonso MD, Dávila I, Conde Salazar L, Cuevas M, Martín JA, Guimaraens MD, et al. Occupational protein contact dermatitis from herring. Allergy. 1993;48(5):349-52.
  27. Kuehn A, Hilger C, Graf T, Hentges F. Protein and DNA-based assays as complementary tools for fish allergen detection. Allergol Select. 2017;1(2):120-6.
  28. Sletten GVD, T. Lindvik, H. Egaas, E. Florvaag, E. Effects of industrial processing on the immunogenicity of commonly ingested fish species. Int Arch Allergy Immunol. 2010;151(3):223-36.
  29. WHO/IUIS. Clu h 1. Clupea harengus 2020. Available from: http://www.allergen.org/viewallergen.php?aid=222.