Allergen Data Collection: Codfish (Gadus morhua)
Internet Symposium on Food Allergens 1(3): 121-134  (1999) [http://www.food-allergens.de
1 Prevalence of Codfish Allergy
 
Country / Subjects Sensitivity to References
Finland, Oulu
children with atopic dermatits
fish 5.3%, 12%, and 9.5% in patients < 1, 1-3 and 3-15 years of age (n=57, 43 and 42) (SPT) Hannuksela 1987
France
81 cases of anaphylactic shock to food
fish 10.4% Moneret-Vautrin & Kanny 1995
France, Pierre Benite
patients with anaphylactic reactions to food
fish 13% Andre et al. 1994
France, Toulouse
142 food allergic children
codfish 5.6 % (labial food challenge) Rance & Dutau 1997
France, Toulouse
378 food allergic children
codfish 7.1% (food challenge) Rance et al. 1999
Germany,Bonn
150 children allergic to egg white, milk, codfish, wheat, peanut and/or soybean
codfish 5.3% (RAST) Liappis & Starke 1999
Italy
134 patients with atopic dermatitis
codfish 5.2 % (case history), 10% (RAST) Bonifazi et al. 1978
Italy, Florence
food allergic children
codfish 18 % (SPT, RAST)
from which 66 % had clinical symptoms
Novembre et al. 1988
Vierucci et al. 1989
Italy, Florence
a) 558 children with atopic diseases
b) children of general population
a) codfish 4.5 % (SPT, RAST)
b) codfish 0.4-0.5 % (calculated)
de Martino et al. 1993
Norway, Oslo
fish allergic children
codfish 88 % Aas 1966
Spain, Madrid
355 food allergic children
fish (cod, tuna) 30 % (SPT, RAST) Crespo et al. 1995
Switzerland, Zurich
402 food allergic adults
fish 7.2 % Wüthrich 1993
USA, Baltimore, MD
20 fish- sensitive  patients with atopic dermatitis
fish 55% (DBPCFC) Sampson & Ho 1997
USA, Denver, CO
180 food allergic children
fish 3% (DBPCFC) Bock & Atkins 1990
USA, Little Rock, AR
165 patients with atopic dermatitis
codfish 6.7% (SPT) from which 3/9 were DBPCFC-positive Burks et al. 1998
USA, Long Beach, CA
137 patients with latex allergy
fish 1.7 % (convincing history of possible IgE mediated symptoms occurring within 60 minutes of ingestion) Kim & Hussain 1999
USA, Portland, ME
39 fish sensitive adults
codfish 31 % (case history), 46 % (SPT), 67 % (RAST)
to all tested 17 fish species 26 % (SPT)
Helbling et al. 1996

2 Symptoms of Codfish Allergy
 
Symptoms & Case Reports References
systemic reactions
anaphylaxis (6, 7, 9, 10, 14, 12)

cutaneous symptoms
angioedema (2, 3, 8, 15), ekzema (2), itching in eyes (14), quincke edema (11), urticaria (2, 3, 8, 11, 13, 15), contact urticaria (4, 5), generalized urticaria (5, 14)

gastrointestinal symptoms
itching in throught (14), oropharyngeal itching and swelling (7), vomiting (3)

respiratory symptoms
allergic rhinitis (15), asthma (1, 2, 8, 13), cough (14), cyanosis (11), dyspnea (14), wheeze (11, 14)
 

(1) DeBesche 1937
(2) Aas 1978
(3) Bonifazi et al. 1978
(4) Beck & Knudsen-Nissen 1983
(5) Ferre et al. 1985
(6) Yunginger et al. 1991
(7) Hansen & Bindslev-Jensen 1992
(8) de Martino et al. 1993
(9) Andre et al. 1994
(10) Moneret-Vautrin & Kanny 1995
(11) Casimir et al. 1997
(12) James et al. 1997
(13) Bugajska-Schretter et al. 1998
(14) Lin et al. 1998
(15) Patriarca et al. 1998
Percentage of Reactions
60 % asthma, 34 % urticaria-angioedema in 68 codfish allergic children (1)

Cutaneous 91%, gastrointestinal 64%, respiratory 9% in 11 fish allergic  patients with atopic dermatitis (3)

69% pruritus, 69% hives, 54% asthma / wheezing, 51% angioedema, 18% dyspepsia / cramps, 8% vomiting, 8% shock and 5% fainting in 39 fish sensitive adults (2)

(1) de Martino et al. 1993
(2) Helbling et al. 1996
(3) Sampson & Ho 1997
Threshold of Ingestion
Amounts of codfish inducing symptoms ranged from 6 mg to 6.7 g (anaphylactic reactions 25-50 g) (DBPCFC, 10 codfish allergic adults) (1)
(1) Hansen & Bindslev-Jensen 1992

3 Diagnostic Features and Therapy of Codfish Allergy
 
Parameters / Subjects Outcome References
Onset of Symptoms, Male:Female Ratio, IgE-level
a) 68 codfish allergic children
b) 533 children allergic to other inhalant and/or food allergens
Age of onset of asthma significantly lower in codfish allergic children (P <0.001):
a) 32 months, b) 41 months
Significant higher male:femal ratio in codfish allergic children:
a) 3.53, b) 1.78 and 0.68 in children allergic to inhalants and foods
Significant higher specific serum IgE in codfish allergic children (P <0.001, RAST):
a) 14.27 +/- 3.87 kU/L
b) 8.12 +/- 4.06 kU/L
de Martino et al. 1993
SPT and IgE
codfish allergic adults
Significant correlation between SPT and RAST (P<0.0005) Helbling et al. 1996
SPT, IgE and Clinical Relevance
20 codfish allergic patients
SPT and RAST were found to be reliable for the diagnosis of allergy to codfish Aas 1978
SPT, IgE, Histamine Release and DBPCFC
10 codfish allergic adults
For identification of DBPCFC-positive subjects, skin prick test and RAST proved to be the most sensitive tests (7/7) (specifity of all tests  90-97 %) Hansen & Bindslev-Jensen 1992
a) RAST and DBPCFC
b) Histamine Release (HR) and DBPCFC
8 codfish allergic adults
a)  RAST with commercial extracts and fresh food::
sensitivity 100%
specificity 87-100%
b) HR with commercial extracts and fresh food:
sensitivity 83%
specificity 100% 
Hansen et al. 1996
a) RAST and DBPCFC
b) SPT and DBPCFC
food-allergic children with atopic dermatitis
a) predictive values of fish specific IgE > 0.35 kU/L
positive preditive value 49% 
(95% for IgE > 20 kU/L)
negative preditive value 97%
b) predictive values of SPT ( > 3 mm)
positive preditive value 77%
negative preditive value 80%
Sampson & Ho 1997
Immunotherapy
1 fish/codfish allergic child
Uncooked codfish odors and accidentally eaten pieces of codfish were tolerated after therapy (Immunotherapy by subcutaneous injections daily administered following the schedule for insect venom allergy using codfish extracts) Casimir et al. 1997
Oral Desentization
2 codfish allergic patient
A diluted food extract followed by increased pure food was administered following a standardized protocol, at the beginning pretreatment with oral sodium cromoglycate, length of therapy 3 and 5 months, after therapy codfish was tolerated (maintenance dose: 200 g boiled fish / week) Patriarca et al. 1998

4 Composition of Codfish
 

5 Allergens of Codfish
 
Proteins / Glycoproteins Allergen Nomenclature References
Allergen M Gad c 1* Elsayed & Bennich 1975
41-kDa Allergen   Galland et al. 1998
Allergen: 63 kDa   Mata et al. 1994
Allergens: 12, 21, 24, 33, 47, 61 kDa   Hemmens et al. 1989
Allergens: 12, 18, 22, 23, 26, 31, 33, 35, 37, 43, 49, 56, 69, 81, > 97 kDa   Hansen et al. 1996
Allergens: 12, 15, 20, 25, 30, 35, 66, 80, 100, 200 kDa   Bugajska-Schretter et al. 1998
Allergens: 12, 18, 41, 60, 67, 80, 104, 130 kDa   Dory et al. 1998
Allergens: 13, 22, 28, 41, 49, 60 kDa   Galland et al. 1998
* according to latin name of the baltic cod (Gadus morhua callarias)

5.1 Sensitization to Codfish Allergens
 
Country / Subjects Sensitivity to References
Austria, Vienna
28 codfish allergic patients
12 kDa allergen (Gad c 1) in 100 %
(SDS-PAGE immunoblot)
Bugajska-Schretter et al. 1998
Denmark, Copenhagen
8 codfish allergic adults
12-13 kDa allergen in 100 % of DBPCFC- positive patients (SDS-PAGE immunoblot) Hansen et al. 1996
France, Nantes
12 codfish allergic patients
12 kDa allergen: relative IgE- binding 50 %
30 and 67 kDa allergens: about 10 %
of total IgE binding to crude extract (pooled serum, SDS-PAGE immunoblot)
Dory et al. 1998
Norway, Bergen (a)
Australia, St. Leonards (b)
a) 2 codfish , b) 1 fish allergic patient
6 allergens recognized by all patients' sera, relative intensity of IgE- binding: 12 kDa >> 21, 24 kDa > 33, 47, 61 kDa (SDS-PAGE immunoblot) Hemmens et al. 1989
Norway, Oslo
codfish allergic patients
At least 7 IgE- binding precipitates (CRIE) Aukrust et al. 1978

5.2 Allergen M (Gad c 1)
5.3 41-kDa-Allergen
 

6 Isolation & Preparation
 
Extract / Purified Allergens Methods References
Protein extract Extraction of raw and cooked fish with PBS-buffer overnight at 4°C, centrifugation, lyophilization Bernhisel-Broadbent et al. 1992
Muscle and Surimi extract Extraction of raw codfish and surimi with 2 % sodium chloride solution for 18 h, centrifugation, purification by gelfiltration (Sephacryl S200) Mata et al. 1994
Muscle extract Homogenization of raw muscle under liquid nitrogen, dissolved in electrophoresis sample buffer Bugajska-Schretter et al. 1998
Muscle extract Fillets of pre- rigor mortis and post- rigor mortis codfish were cut and placed into liquid nitrogen, crushed and homogenized in phosphate- buffer (for sarcoplasmic proteins) or PBS-buffer (for myofibrillar proteins) at 4°C, centrifuged and lyphilized Dory et al. 1998
Allergen M Purification of myogen fraction by ion-exchange chromatography (DEAE) and gelfiltration (Sephadex G-75) Aas & Jepsen 1967
Aas & Elsayed 1969
Allergen M Purification of myogen fraction by isoelectric fractionation Elsyed & Aas 1971
41-kDa Allergen Isolation from a crude cod extract by ammonium sulfate fractionation, hydroxyapatite chromatography and preparative electrophoresis Galland et al. 1998


7 Cross-Reactivities
 
Cross-Reacting Allergens Subjects / Methods References
Codfish
bass, dentex, eel, sole, and tuna (17 different fish species tested)
High frequency of sensitization to eel (85%) and to bass, dentex, sole, and tuna (55%) in cod-positive children, least frequent was dogfish (10%) (SPT)
Cross-reacting allergens in cod, bass, dentex, eel, sole, and tuna, inhibition range from 73 - 96 % (RAST inhibition)
de Martino et al. 1990
Codfish
10 different fish species (bass, catfish, flounder, mackerel, perch, salmon, trout, tuna, sardine)
11 fish allergic patients: 7 patients sensitive to only 1 species, 1 patient to 2 species, and 2 patients to 3 species (oral challenge)
8 patients sensitive to all 10 species in SPT
Cross-reactivity did not necessarily correlate with clinical relevance (RAST inhibition)
Bernhisel-Broadbent et al. 1992
Codfish
mackerel, herring, and plaice
Inhibition of IgE- binding to codfish extract by mackerel, herring, and plaice in 8 codfish allergic patients, no cross-reactivity to shrimp or milk
(RAST inhibition)
Hansen et al. 1997
Codfish
catfish, dogfish, snapper  (12.5 kDa allergens)
Inhibition of IgE- binding to 12.5 kDa allergens by codfish extract (immunoblot inhibition) James et al. 1997
Codfish
tuna, salmon, perch, carp, and eel
Inhibition of IgE- binding to extracts from tuna, salmon, perch, carp, and eel by codfish ranged from 43 - 97 % in 4 fish allergic patients (RAST inhibition) Bugajska-Schretter et al. 1998
Codfish
tuna, salmon, perch, carp, and eel (12 kDa)
Inhibition of IgE- binding to 12 kDa parvalbumins from different species by codfish extract (immunoblot inhibition) Bugajska-Schretter et al. 1998
Codfish Allergens (12 kDa)
17, 21, 24, and 47 kDa- codfish allergens *
Gad c 1 (12 kDa) bound IgE was eluted and rebound to 12, 17, 21, 24, and 47 kDa allergens in 1 patient, while in another patient IgE rebound only to 12 kDa allergen (SDS-PAGE immunoblot) Hemmens et al. 1989
Codfish Allergens
12, 22, 25, 30, 45, 50, 60, 67, 80, 104, and 130 kDa- codfish allergens *
Exept for the 41, 49, and 55 kDa allergens all IgE- binding proteins from codfish were detected by antiparvalbumin specific antibody (SDS-PAGE immunoblot) Dory et al. 1998
*  multiple sensitization / reactivity (not proved by inhibition-tests)
 

8 Stability of Codfish Allergens
 
Treatment Effects References
Cod myogen fraction
enzymic digestion for a) 48 h, b) < 24 h and c) < 2 h at 37°C (stopped by heating to 80°C, 10 min)
a) Loss of allergenic activity by treatment with trypsin, pepsin, subtilisin or pronase, appr. 50% decrease in allergenic activity by elastase
b) Remaining allergenic activity by pronase treatment
c) Remaining allergenic activity by trypsin or pepsin treatment
Aas & Elsayed 1969
Codfish Allergens
9 household cleaning solutions and 5 chemical detergents mixed with codfish allergen extract, incubation for 20 min at RT
Guanidine hydrochloride and sodium lauryl sulphate induced  some modifications of allergen patterns;
None of the detergents totally destroyed the allergenic activities, even when used in concentrations up to 10 times than recommended
(CIE, CRIE, serum pool of  >5 patients)
Dybendal et al. 1990
Codfish Allergens
raw and cooked codfish
Number of protein bands in raw and cooked codfish: 25 and 23, respectively (SDS-PAGE)
Lower intensity of IgE- binding to allergens from cooked codfish (SDS-PAGE immunoblot)
Bernhisel-Broadbent et al. 1992
Pizza Toppings
uncooked and cooked pizza toppings
IgE-binding to uncooked pizza topping extract was inhibited by cooked pizza toppings (max. 76%), pollack (max. 59%), cod (max. 30%), and surimi (max. 52%) (30 fish sensitive patients, RAST inhibition) Helbling et al. 1992
Codfish Allergens
a) pre- and post-rigor mortis
b) stored commercial codfish (several days)
a) No difference in IgE- binding patterns
b) Storage might increase relative IgE- binding, additional bands 18, 41, and 80 kDa allergens (RAST inhibition, SDS-PAGE immunoblot)
Dory et al. 1998

9 Allergen Sources
 
Reported Adverse Reactions References
Food / Food additives
Fatal anaphylactic reaction in fish allergic patient after ingestion of potatoes fried in same oil that has been used for fish (1)
Anaphylactic reactions in fish allergic boy after ingestion of different kinds of fish (cod, tuna, salmon, trout, eel...), fish soup, chopsticks contaminated with fish preparations or canned fish (2)
(1) Yunginger et al. 1988
(2) Lin et al. 1998

 
Allergens in Codfish Products Results References
Codfish Allergens
63 kDa allergen in surimi, a Japanese food product containing fish meat and may contain starch, egg white, and other ingredients
 Surimi extract gave positive reactions in 6 codfish allergic patients  (RAST, RAST inhibition, Histamine Release, SDS-PAGE) (1) Mata et al. 1994
Fish Allergens
Fish allergens in surimi and pizza toppings
Extracts of surimi, uncooked and cooked pizza toppings gave positive reactions in fish sensitive patients  (RAST, RAST inhibition) (1) Helbling et al. 1992
Anisakis simplex
Anisakis simplex, a parasite of fish and cephalopods
Specific IgE to A. simplex (> 0.7 kU/l) in 22 patients with urticaria/angioedema after fish ingestion, from which 8 were diagnosed as having A. simplex allergy (RAST, clinical symptoms) (1) Del Pozo et al. 1997

 
Other Allergen Sources References
Dust
Dust samples from fitted-carpets and linoleum floors in schools in Norway contained codfish allergens, higher contents in samples from carpets  (1)
(1) Dybendal et al. 1989a, 1989b

10 References

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