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Allergen Encyclopedia
Table of Contents

Whole Allergen

f3 Cod

f3 Cod Scientific Information

Type:

Whole Allergen

Display Name:

Cod

Route of Exposure:

Ingestion

Family:

Gadidae Rafinesque

Species:

Gadus morhua

Latin Name:

Gadus morhua

Other Names:

Atlantic Cod, Cod (Canada), Morue (France), Dorsch, Kabeljau (Germany)

Summary

Cod (family Gadidae) is an economically important fish distributed in the northwest Atlantic Ocean found in Canadian waters, Greenland, and North Carolina. It is a cold-water fish, which can survive in nearly freezing to 20oC temperature and found in both fresh and marine water. Cod protein content is usually between 15-20% of their body weight. In codfish, the major allergen is the muscle protein parvalbumin, which is a calcium-binding protein. Parvalbumin is also known as “Gad c 1”, and it is the first calcium-binding allergen characterized from codfish, which cannot be destroyed by heat or cooking. Hence, if the individual or sensitized person is exposed to the cod allergen through oral, nasal or occupational route, the allergen triggers an allergic reaction. Detection of codfish allergy is based on clinical history, skin prick test, and specific IgE and immunoblotting tests.

The codfish cross reactivity was closely related to mackerel (Perciformes), herring (Clupeiformes), and plaice (Pleuronectiformes). Also, cods parvalbumins (Gad c 1) cross react with parvalbumins from salmon (Sal s 1), and pollack (The c 1).

Allergen

Nature

The Atlantic cod is an economically important marine fish which can attain ages of 20 years. Adult codfish has a large head and heavy-body.  The snout is blunt and the lower jaw tip has a barbel on the dorsal side. Color varies with small spots and pale lateral line in their body. Their average weight is around 25-35 kg and they can grow up to a length of 130 cm. Sexual maturity occurs at a median age of around 1.7-2.3 years with lengths ranging from 32-41 cm (1). 

Habitat

The codfish is found in Canada that includes the east coast of Labrador, south of Cape Harrison, east Newfoundland, Flemish Cap, Grand Bank, Gulf of St. Lawrence and Scotian Shelf. Young stages in Atlantic where cod tends to be restricted around major spawning centers (1).

Taxonomy

Table 1: Taxonomic tree of Codfish (2)

Epidemiology

Worldwide distribution

Prevalence rates of fish allergy are 0.7 % in the global population. Higher prevalence was observed in the pediatric groups and in long coastline countries with fish as a staple food and fish-processing industries (4). A cross-sectional, random telephonic national survey conducted in the USA reported 3.3% of the general population has a seafood allergy (5). 

Environmental Characteristics

Living environment

Cod tends to move in deeper, colder and saline water with increasing age. They are found on or near the bottom along rocky slopes and ledges in depth ranging from 40-130 m but rarely found at 200 m. Cod can survive temperature ranging from near freezing to 20°C. However, during the fall they are found in warmer temperatures compared to temperatures of < 10°C where they are usually found (1).

Worldwide distribution

Cod is distributed in the northwest Atlantic Ocean from Greenland to Cape Hatteras in North Carolina. The density in the Gulf of St. Lawrence, Scotian Shelf Georges Bank, and the western Gulf of Maine are the highest (1).

Route of Exposure

Main

The route of exposure is mainly an oral route through consumption, but touch and inhalation of fish and related products can as well trigger allergic reactions (6).

Detection

Detection of allergy is based on clinical history, skin prick test, specific IgE tests, histamine release test, and immunoblotting, followed by oral fish challenge. Serum IgE antibodies levels are estimated along with the clinical reactivity to predict fish allergy (7). 

Clinical Relevance

In cod allergic patients, incomplete digestion of cod can lead to anaphylaxis. While in non-allergic subjects, fish allergens are identified within 10 min and reach a peak in 1-2 hrs. after ingestion. Digestive enzymes cause protein fragmentation, which reduces biological activity. However, increasing pH to 3.0 for digestion leads to reactivity patterns comparable to undigested extracts (8).

Codfish allergy symptoms can affect single or multiple organs, ranging from mild to severe anaphylaxis. Clinical symptoms start in less than 1 min after fish exposure. This can lead to cutaneous (urticaria, angioedema), GI (oral allergy syndrome, laryngeal edema, spasm, diarrhea, vomiting), and respiratory (rhino-conjunctivitis, bronchospasm) and severe anaphylaxis in some cases (6).

Prevention and Therapy

Prevention strategies

Avoidance

Fish allergic individuals should strictly avoid fish in any form including fish-derived products (9).

Molecular Aspects

Allergenic molecules

In fish and amphibians, calcium-binding proteins (CBPs) are important food allergens. The first calcium-binding allergen characterized was parvalbumin from codfish (10). The most common allergen in codfish is a muscle protein (CBPs) called parvalbumin, also known as “Gad c 1”. It is a major allergen, extremely stable to heat, with a low-molecular-weight (10–12 kDa), commonly found in fish muscle (9).  

Table 3: WHO/IUIS registered fish allergens (4)

Fish Species  Allergen Protein type 

Baltic cod  

(Gadus callarias)

Gad c 1 β-parvalbumin

Atlantic cod

 (Gadus morhua)

Gad m 1

Gad m 2

Gad m 3

β-parvalbumin

β-enolase

Aldolase A

Cross-reactivity

A study by Hensen in 1997, showed that all clinically codfish-sensitive adults have serological cross-reactivity to other fish species (7).

The parvalbumins from salmon (Sal s 1), pollack (The c 1) showed high identity indices with the amino acid sequence of cod (Gad c 1), which supports the cross-reactivity between these fish species (11).  The identity indices of Gad c 1 amino acid sequence were similar to parvalbumins from Sal s 1 (68%) and the c 1 (62%), which highlights the cross-reactivity (11). 

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Fabio Iachetti

 

Last reviewed: October  2020

References
  1. Lough R. ssential fish habitat source documents: Atlantic cod, Gadus morhua, life history and habitat characteristics (2nd edition)” (National Oceanic and Atmospheric Adminstration, . Tech Memo NMFS NE, Woods Hole, MA, 2004. 2004.
  2. Gadusmorhua. Integrated Taxonomic Information System (ITIS) 2020.
  3. FAO. The Composition of Fish 2020 [2020-10-15]. Available from: http://www.fao.org/3/x5916e01.htm#Introduction.
  4. 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.
  5. Sicherer SH. Prevalence of seafood allergy in the United States determined by a random telephone survey. J Allergy Clin Immunol. 2004;114(1):159-65.
  6. Klueber. Fish Allergy Management: From Component-Resolved Diagnosis to Unmet Diagnostic Needs. Curr Treat Options Allergy 2019;6:322–37. 2019.
  7. Hansen TK, Bindslev-Jensen C, Skov PS, Poulsen LK. Codfish allergy in adults: IgE cross-reactivity among fish species. Ann Allergy Asthma Immunol. 1997;78(2):187-94.
  8. Untersmayr E, Vestergaard H, Malling HJ, Jensen LB, Platzer MH, Boltz-Nitulescu G, et al. Incomplete digestion of codfish represents a risk factor for anaphylaxis in patients with allergy. J Allergy Clin Immunol. 2007;119(3):711-7.
  9. Kuehn A, Swoboda I, Arumugam K, Hilger C, Hentges F. Fish allergens at a glance: variable allergenicity of parvalbumins, the major fish allergens. Front Immunol. 2014;5:179.
  10. Wopfner N, Dissertori O, Ferreira F, Lackner P. Calcium-binding proteins and their role in allergic diseases. Immunol Allergy Clin North Am. 2007;27(1):29-44.
  11. 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.