Allergy information for: Mackerel (Scomber japonicus, Scomber scombrus, Scomber australasicus)

  • Name: Mackerel
  • Scientific Name: Scomber japonicus, Scomber scombrus, Scomber australasicus
  • Occurrence: Mackerel from both recreational catches and commercial landings is eaten after cooking from fresh fish. Mackerel may occur in some mixed seafood dishes. Canned mackerel may have reduced allergenicity as is found with tuna.
  • Allergy Information:

    Allergy to fin fish is relatively common (0.4% of adults in the USA according to one telephone survey), and can be associated with severe symptoms such as anaphylactic shock. Symptoms can also occur after ingestion of only a small quantity of fish with one reported reaction in an individual after receiving a kiss from someone who had recently eaten fish. Allergy to fish is not to be confused with a toxic reaction to histamine in spoiled fish (scombroid fish poisoning).

    Almost all fish allergy seems to involve the protein parvalbumin, which is found in the muscle of most fish. As the parvalbumins are similar in all fish species, individuals allergic to one fish are likely to react to a range of different fish species. Thus after a diagnosis of allergy to one fish species, patients are normally advised to avoid all fin fish. Some individuals also react to frog. Although fin fish and shellfish allergies are not linked, individuals can be allergic to both foods.

    Parvalbumin remains able to cause a reaction after cooking. Thus fish remains allergenic after cooking and other treatments. Fish can be a "hidden" allergen in, for example, pizza toppings. Consequently, the EU labelling regulations require foods containing fish and products thereof to be labelled.

    Supplementary information on Fish Allergy

    Fish and fish products play an important role in human nutrition. Fish is a valuable source of proteins and contains large amounts of healthy fats (so called polyunsaturated fatty acids) and fat-soluble vitamins. However, it also is one of the most common causes of food allergy. Fish allergy is a so-called IgE-mediated food allergy. IgE (Immunoglobulin E) is the allergy antibody.

    Allergy to fish is caused by a reaction to protein in fish meat (muscle). The dominating allergen is a muscle protein called parvalbumin. In professional literature this allergen is often referred to as “Gad c 1” from the Latin name for cod fish Gadus callarias. This major allergen is extremely stable to heat, which means that boiling or frying of fish does not destroy the allergen. Other proteins in fish have been described as allergens, but most reactions to cod (and other fish; see under Related foods) are most likely caused by this one allergen

    Symptoms

    Reactions can be severe and even life-threatening. The severity of symptoms may vary according to the amount ingested and the sensitivity of the person. Often the first symptom is irritation and itching in mouth and throat appearing few minutes after the intake. It can be followed by other allergic reactions such as nausea, vomiting, stomach ache, diarrhoea, hives (also called urticaria or nettle rash), swelling under the skin (also called angioedema), itching and reddening of the skin, worsening of eczema, asthma (wheezing, breathlessness, coughing), hay fever (itchy nose and eyes, sneezing/runny nose), swelling of the airways, and sometimes fatal episodes of allergic shock. Usually a combination of several symptoms is seen.

    Spoiled fish can contain a substance called histamine. This is the same substance that is produced by cells of an allergic patient during an allergic reaction. It is involved in the induction of symptoms. Spoiled fish can elicit symptoms in every person having eaten it. The reaction is similar to an allergic reaction, i.e. swelling, hives, wheezing etc., but it is poisoning.

    Related foods (cross-reactions)

    Most information on fish allergy is gathered on codfish. The variety of fish eaten around the world is immense. Despite this, fish species known to cause allergy belong to a few closely related orders: codfish and hake (Gadiformes), mackerel, tuna and perch (Perciformes), salmon and trout (Salmoniformes), plaice and sole (Pleuronectiformes), herring, anchovy and sardine (Clupeiformes), carp and catfish (Cypriniformes), and eel (Anguilliformes). Patients with allergy to codfish are often allergic to the other fish species as well. This can be explained by similarity of the allergen parvalbumin in all fish species. Allergic reactions based on such similarity are called cross-reactions. The cross-reactivity between fish species is certainly not complete. Some patients are allergic to one and tolerate other species.

    Allergy to fish does not mean that other seafood like shellfish is not tolerated. Cross-reactivity is irrelevant between fish and shellfish. Of course, patients can develop allergy to both independently. Fish roe (or caviar) has been reported to cause food allergy but there is no relation to allergy to the fish from which the eggs originate.

    Finally, it has been reported that parvalbumin in frogs legs can in some cases also cause allergy in fish allergic patients. This again is cause by cross reactivity.

    Who, when, how long and how often?

    Food allergy to fish is seen both among children and adults (approximately 0.1-0.2%). Varieties in food habits according to country influence the frequency patterns of fish allergy, with the number of fish allergics being higher in those countries where fish is a major component of the local diet. In general, fish allergy is not outgrown but it persists through life.

    How much is too much?

    Care has to be taken since very small amounts (few mg, in other words a tiny flake) of fish can elicit a reaction in very sensitive persons. A dose of only 5 mg of cod has been described to cause reaction. Furthermore, some fish allergic persons can get allergic symptoms due to the steam (airborne allergens) from cooking fish. Fish allergy is therefore sometimes a problem in the fish industry and among restaurant cooks, where handling and inhalation might cause eczema and asthma. Finally, even a kiss of somebody that has eaten fish can induce a reaction in a fish allergic person.

    Diagnosis

    An indication for IgE-mediated fish allergy can be obtained from skin prick testing and from serum IgE testing. The presence of a positive skin prick test or of fish protein-specific IgE-antibody in serum is indicative of an IgE-mediated fish allergy, but both tests may be false-positive or false-negative. Therefore, a definitive diagnosis has to be based on strict, well-defined elimination and re-introduction protocols or on controlled fish challenge procedures. Fish allergy is confirmed if symptoms disappear after elimination and re-appear upon re-introduction or if a so-called double-blind placebo controlled food challenge gives a positive result. During such a challenge both doctor and patient do not know which challenge meal contains fish and which does not. Such challenge procedures are also helpful in determining the threshold dose of reactivity, and to verify if a person has outgrown the food allergy, although this is rarely seen with fish allergy.

    Where do I find fish?

    It is important to study the labels on processed foods since various products can contain fish: surimi (fish product imitating crabmeat), fish meal, animal fat, liver pâté, some sausages, crab salad, sushi, oyster sauce, Worcestershire sauce, Caesar salad, tapenade, and pizza toppings. Fish oils/animal oil can also contain fish proteins, depending on the degree of refining of the oil. Fish gelatine made from skin and bones and used in food products is not considered to present a risk to fish allergic persons at the doses typically used.

    Non-food products

    Fish gelatine is applied in pharmaceutical products like vaccines, but it is not considered a risk to fish allergic persons.

    Avoidance

    If suffering from fish allergy, strict avoidance of fish in any form and food containing fish-derived ingredients is the only way to prevent a reaction. This can sometimes be difficult because they can be hidden in food products. According to the new EU labelling directive (2003/89/EC) and the list of the Codex Alimentarius Commission, any fish-derived ingredient has to be listed on the label. Even if labels are carefully read, unintentionally and accidentally consumption of fish may happen. Fish allergic individuals should especially be cautious when eating away from home. When ordering a “non-fish meal” at a restaurant it may be contaminated with fish proteins from utensils, cooking oil or a grill exposed to fish.

  • Other Information:

    Fish and products thereof are listed in annex IIIa of the EU directive on labelling of foods.

  • Taxonomic Information:

    The Atlantic mackerel (Scomber scombrus, NEWT 13676), Chub mackerel (Scomber japonicus, NEWT 13677), and blue mackerel (Scomber australasicus, NEWT 29150) are closely related species.

    The horse mackerel (Trachurus novaezelandiae, NEWT 271942), which has also been reported as an allergenic food, is only distantly related.
  • Last modified: 18 October 2006

Reviews (0)

    References (0)

      Clinical History

      • Number of Studies:1-5
      • Number of Patients:21-50
      • Symptoms:

        Most articles mentioning allergy to mackerel describe allergy to fish in general without attributing symptoms specifically to mackerel. 

        Hamada et al. (2003) [1395] list the symptoms of the 5 patients who provided sera as urticaria in all 5 cases with additional symptoms of asthma for one patient and diarhoea for another.

        Helbling et al. (1996) [1727] describe the symptoms of 39 patients as pruritus (27/39), hives (27/39), asthma and wheezing (21/39), angioedema (20/39), dyspepsia and cramps (7/39), vomiting (3/39), shock (3/39) and fainting (2/39). Only 4/39 patients had a history of allergic reaction following ingestion of mackerel but 20/39 had a positive SPT and 9/23 a positive RAST to mackerel.

        Bernhisel-Broadbent et al. (1992) [1397] describe symptoms on challenge with other fish species as oral pruritis in 10/11 patients together with cutaneous symptoms (urticaria, angioedema, pruritis or erythema) in 6, gasterointestinal in 2, while one patients showed laryngeal symptoms and another wheeze.  

        de Martino et al (1990) [1681] also noted that 1/20 cod allergic children had a clinical history of reaction to mackerel although only 4/20 children reported ever eating mackerel. 

      Skin Prick Test

      • Number of Studies:1-5
      • Food/Type of allergen:

        Helbling et al. (1996) [1727] made an extract of Alaska pollack and of 4 crustacean species. 16 commercial extracts of fish, including mackerel, and 12 commercial extracts of inhalant allergens were also used .

        Bernhisel-Broadbent et al. (1992) [1397] added 10 g. of raw or cooked fish (catfish, bass, perch, mackerel, tuna, salmon, trout, codfish and flounder) to 40 ml. phosphate buffered saline in centrifuge tubes with a glass marble. The tubes were placed in a test tube rotator overnight at 4°C. Samples were centrifuged at 1250 x g for 15 min and then at 16000 x g for 15 min. Supernatants were lyophilized. Skin tests used extracts of raw fish, probably reconsituted 1:20 (w/v). Commercial sardine extract was used (Greer laboratories, Lenoir, NC). 

        de Martino et al (1990) [1681] used commercial extracts (Lofarma, Milan, Italy). The extracts were diluted 1:20 (w/v) in a glycerol solution.

      • Protocol: (controls, definition of positive etc)

        Helbling et al. (1996) [1727] defined a positive skin prick as producing a 3 mm diameter wheal in a patient who reacted to the positive control (1 mg/ml histamine diphosphate) and not to 50% (v/v) glycerol in PBS. Results were recorded after 15 minutes.

        Bernhisel-Broadbent et al. (1992) [1397] used 1 mg/ml histamine as a positive control and saline as a negative control. Wheal with diameters 3 mm greater than the negative control were considered positive.

        de Martino et al (1990) [1681] used histamine hydochloride, 1 mg/ml, as a positive control and a glycerol solution as a negative control. Diameters were read after 15 minutes and reactions half or more than the size of the positive control, read after 10 minutes, were considered positive. 

      • Number of Patients:

        Helbling et al. (1996) [1727] tested 35 out of 39 study subjects with mackerel together with 18 atopic control subjects.

        Bernhisel-Broadbent et al. (1992) [1397] tested 11 patients with histories of fish allergy and 20 controls including 10 atopic patients with other food allergies.

        de Martino et al (1990) [1681] tested 20 cod allergic children and 40 children who had a positive SPT and RAST to a different food.

      • Summary of Results:

        Helbling et al. (1996) [1727] found that 21/35 fish allergic subjects gave a positive skin test to mackerel. One atopic control subject also reacted.

        Bernhisel-Broadbent et al. (1992) [1397] reported that 8/11 patients gave positive SPTs with mackerel extract. The wheal diameters of positive tests were 6-26 mm. For comparison, the least reactive was sardine with 8 positive and 4-8 mm diameters while cod extract produced 9/11 positive wheals with 4-40 mm diameters.

        de Martino et al (1990) [1681] reported that only 4/20 of the cod allergic children reacted to mackerel extract and none of the cod negative children reacted.

      IgE assay (by RAST, CAP etc)

      • Number of Studies:0
      • Food/Type of allergen:

        Hamada et al (2004) [1392] used natural and recombinant parvalbumin from pacific mackerel, Scomber japonicus.

        Hamada et al (2003) [1395] used purified parvalbumin from pacific or chub mackerel, Scomber japonicus, Atlantic mackerel (Scomber scombrus) and blue mackerel (Scomber australasicus).

        Hamada et al (2003) [1800] used purified collagen from Japanese eel, alfonsin, mackerel, skipjack and bigeye tuna and also purified parvalbumin from bigeye tuna.   

        Helbling et al. (1996) [1727] made an extract of Alaska pollack, anchovy, mackerel, rainbow trout, salmon and tuna by blending 500g of raw fish in 1L of 0.01M PBS, pH 7.2, in a Waring blender for 1-3 minutes at room temperature. The mixture was extracted overnight at 4°C and centrifuged (70,000 x g). Supernatants were concentrated  with an Amicon YM1 filter (molecular weight cut-off 1 kDa) and recentrifuged (180,000 x g). Commercial extracts of bass, catfish, codfish, haddock, perch, sardine, herring, snapper, sole and whitefish were dialysed against 0.1 M borate, ph 8.0, and concentrated by dialysis against Ficoll 400 (Pharmacia). Cyanogen bromide activated paper disks were loaded to 50 μg protein per disk for RAST.

        Bernhisel-Broadbent et al. (1992) [1397] used the extracts described for skin tests.

      • IgE protocol:

        Hamada et al (2004) [1392] used ELISA and ELISA inhibition.

        Hamada et al. (2003) [1395] and Hamada et al (2003) [1800] used CAP-RAST, ELISA, and ELISA inhibition.

        Helbling et al. (1996) [1727] used RAST and RAST inhibition. A positive RAST was ≥3% binding of the added radioactivity.

        Bernhisel-Broadbent et al. (1992) [1397] used immunoblotting.

      • Number of Patients:

        Hamada et al (2004) [1392] used sera from 2 fish allergic patients.

        Hamada et al (2003) [1395] used sera from 5 fish allergic patients.

        Hamada et al (2003) [1800] used sera from 15 fish allergic patients.

        Helbling et al. (1996) [1727] used sera from 23 fish allergic patients.

        Bernhisel-Broadbent et al. (1992) [1397] used sera from 11 fish allergic patients

      • Summary of Results:

        Hamada et al (2004) [1392] reported an IgE binding inhibition study of natural and recombinant mackerel (Scomber japanicus) parvalbumin against purified parvalbumins from Japanese eel, horse mackerel, red sea bream, skipjack, bigeye tuna and Japanese flounder. They concluded that there was significant IgE cross-reactivity between mackerel and other fish parvalbumins and that the recombinant mackerel parvalbumin could be used to diagnose fish-allergy.

        Hamada et al. (2003) [1395] report the CAP-RAST classes of their 5 subjects:
        Subject 1 - salmon (3) and cod (3)
        Subject 2 - salmon (4) and cod (3)
        Subject 3 - salmon (3), cod (3), horse mackerel (3) and mackerel (3)
        Subject 4 - sardine (3), salmon (3), cod (3), horse mackerel (3), mackerel (3) and tuna (3)
        Subject 5 - cod (4), horse mackerel (3), mackerel (3) and tuna (4)
        By ELISA, four of the five patient sera tested reacted to all the purified mackerel parvalbumins. Serum from patient 5 was found to react to collagen but not to parvalbumin.

        Hamada et al (2003) [1800] also reported CAP-RAST classes against several species of fish for 15 fish allergic patients, probably including some of those of Hamada et al. (2003) [1395]. 4/15 sera were found to react with bigeye tuna collagen by ELISA and 3 of these were tested to show that collagen extracted from Japanese eel, alfonsin, mackerel, skipjack and bigeye tuna gave similar IgE binding.  

        Helbling et al. (1996) [1727] reported a positive RAST with mackerel for 9/23 fish-sensitive subjects, which was the third lowest response rate of the 20 fish tested. The proportion of positive responses varied from 8/11 for cod and 8/12 for haddock to 4/29 for anchovy and 5/27 for tuna. It had been suggested that some positive SPTs with commercial fish extracts were due to histamine contamination and in this study 13/18 and 5/18 atopic controls reacted to anchovy and tuna respectively. However, the correlation for mackerel between RAST and SPT results with 5.2% of radioactivity bound by sera from SPT positive subjects and 1.3% bound by sera from SPT negative subjects suggests that the SPT results were not influenced by histamine. RAST inhibition of mackerel was greatest for anchovy extract, 80% (only slightly less than mackerel extract), with salmon near 40% and tuna near 20%.

      Immunoblotting

      • Immunoblotting separation:

        Bernhisel-Broadbent et al. (1992) [1397] separated proteins by SDS-PAGE by the method of Dreyfuss et al. (1984) [1799].

      • Immunoblotting detection method:Bernhisel-Broadbent et al. (1992) [1397] transferred proteins electrophoretically onto nitrocellulose membranes in Tris-glycine buffer (pH 9.1) containing 20% (v/v) methanol. These were blocked in PBS with 0.5% porcine gelatin and 0.05% (v/v) Tween 20. The membranes were probed with 1:25 (v/v) diluted sera from fish allergic patients. Bound IgE was revealed by biotinylated goat anti-human IgE, followed by reaction with an enzyme horseradish peroxidase-avidin-D solution (Vector Laboratories, Burlingame, CA). 
      • Immunoblotting results:

        Bernhisel-Broadbent et al. (1992) [1397] showed that IgE from the sera of a salmon allergic patient recognised a 13 kDa allergen in extracts of several raw and cooked fish including mackerel. Sera from a flounder allergic patient did not recognise salmon extract but did bind to the 13 kDa band in mackerel. 

      Oral provocation

      • Number of Studies:0
      • Food used and oral provocation vehicle:
      • Blind:
      • Number of Patients:
      • Dose response:
      • Symptoms:No oral challenges have been reported with mackerel.

      IgE cross-reactivity and Polysensitisation

      Hansen et al (1997) [1295] showed that there was IgE cross-reactivity between cod, plaice, herring and mackerel in their 8 patients using skin prick, histamine release and inhibition of IgE binding. This was shown by immunoblotting to be due to parvalbumins in these species related to the parvalbumin Gad c 1 of cod. Similarly, Hamada et al. (2003) [1395] found that IgE from 4/5 patients reacting to salmon, cod, sardine and tuna also bound to the parvalbumins from 3 species of mackerel. Hamada et al (2004) [1392] reported cross-reaction of natural and recombinant mackerel parvalbumin against purified parvalbumins from Japanese eel, horse mackerel, red sea bream, skipjack, bigeye tuna and Japanese flounder. Bernhisel-Broadbent et al. (1992) [1397] found that 8/11 patients gave positive SPTs to mackerel and 8 also reacted by DBPCFC to at least one fish species (mackerel was not used for challenge). The similarity of beta-parvalbumin sequences suggest that there will be cross-reactivity between all the teleost fish species (and possibly to frog). However, the cross-reactivity is not complete with individual patients reacting differently to various fish species (Sicherer et al, 2004 [1375]; Tanaka et al, 2000 [1385]; de Martino et al, 1990 [1681]). Tanaka et al, 2000 [1385] reported that mackerel allergy is most closely associated with allergy to salmon and sardine.

      Other Clinical information

      Scombroid fish (mackerel, tuna, marlin, swordfish, albacore, bonito, skipjack, and almost 100 other species) have a high concentration of histidine which functions to buffer the pH. Thus only a few hours at room temperature can allow bacteria to generate toxic levels of histamine. As histamine is the main mediator of IgE mediated allergic reactions, the symptoms of histamine poisoning are similar to allergy to fish (Ohnuma et al. 2001 [1321]; Attaran & Probst, 2002 [1320]). Several other (non-scombroid) species of fish such as sardines have also been associated with cases of histamine toxicity.

      Reviews (2)

      • Taylor, S. L., Kabourek, J. L., Hefle, S. L.
        Fish allergy: Fish and products thereof
        Journal of Food Science 69 (8) R175-R180.. 2004
        PUBMEDID:
      • Wild LG, Lehrer SB.
        Fish and shellfish allergy.
        Curr Allergy Asthma Rep. 5(1):74-79.. 2005
        PUBMEDID: 15659268

      References (14)

      • Hamada Y, Tanaka H, Sato A, Ishizaki S, Nagashima Y, Shiomi K.
        Expression and evaluation of IgE-binding capacity of recombinant Pacific mackerel parvalbumin.
        Allergology International 53(3), 271-278.. 2004
        PUBMEDID:
      • Hansen TK, Bindslev-Jensen C, Skov PS, Poulsen LK.
        Codfish allergy in adults: IgE cross-reactivity among fish species.
        Ann Allergy Asthma Immunol. 78(2):187-194.. 1997
        PUBMEDID: 9048527
      • Hamada Y; Nagashima Y; Shiomi K
        Reactivity of serum immunoglobulin E to bullfrog Rana catesbeiana parvalbumins in fish-allergic patients
        FISHERIES SCIENCE 70, Iss 6, 1137-1143. 2004
        PUBMEDID:
      • Hamada Y, Tanaka H, Ishizaki S, Ishida M, Nagashima Y, Shiomi K.
        Purification, reactivity with IgE and cDNA cloning of parvalbumin as the major allergen of mackerels.
        Food Chem Toxicol. 41(8):1149-1156.. 2003
        PUBMEDID: 12842183
      • Chopin C, Lardy N, Daniel A, Fleurence J.
        Allergy to mackerel (Scomber scombrus): effect of sterilisation treatment
        SCIENCES DES ALIMENTS 20 (3): 379-385 . 2000
        PUBMEDID:
      • Helbling A, McCants ML, Musmand JJ, Schwartz HJ, Lehrer SB.
        Immunopathogenesis of fish allergy: identification of fish-allergic adults by skin test and radioallergosorbent test.
        Ann Allergy Asthma Immunol. 77(1):48-54.. 1996
        PUBMEDID: 8705636
      • de Martino M, Novembre E, Galli L, de Marco A, Botarelli P, Marano E, Vierucci A.
        Allergy to different fish species in cod-allergic children: in vivo and in vitro studies.
        J Allergy Clin Immunol. 86(6 Pt 1):909-914.. 1990
        PUBMEDID: 2262645
      • Attaran RR, Probst F.
        Histamine fish poisoning: a common but frequently misdiagnosed condition.
        Emerg Med J. 19(5):474-475.. 2002
        PUBMEDID: 12205017
      • Ohnuma S, Higa M, Hamanaka S, Matsushima K, Yamamuro W.
        An outbreak of allergy-like food poisoning.
        Intern Med. 40(8):833-835.. 2001
        PUBMEDID: 11518138
      • Tanaka R, Ichikawa K, Hamano K.
        [Clinical characteristics of seafood allergy and classification of 10 seafood allergens by cluster analysis]
        Arerugi 49(6):479-486.. 2000
        PUBMEDID: 10916886
      • 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. 114(1):159-165.. 2004
        PUBMEDID: 15241360
      • Bernhisel-Broadbent J, Scanlon SM, Sampson HA.
        Fish hypersensitivity. I. In vitro and oral challenge results in fish-allergic patients.
        J Allergy Clin Immunol. 89(3):730-737.. 1992
        PUBMEDID: 1545094
      • Shiomi K; Hayashi S; Ishikawa M; Shimakura K; Nagashima Y.
        Identification of parvalbumin as an allergen in horse mackerel muscle
        FISHERIES SCIENCE 64, Iss 2, pp 300-304. 1998
        PUBMEDID:
      • Hamada Y, Nagashima Y, Shiomi K, Shimojo N, Kohno Y, Shibata R, Nishima S, Ikezawa Z.
        Reactivity of IgE in fish-allergic patients to fish muscle collagen.
        Allergology International 52(3), 139-147. 2003
        PUBMEDID:

      Biochemical Information for Parvalbumin

      • Allergen Name:Parvalbumin
      • Alternatve Allergen Names:Sco j 1, Sco a 1 or Sco s 1 (not in IUIS list) from Scomber japonicus, S. australasicus and S. scombrus respectively (chub mackerel, blue mackerel and Atlantic mackerel).
      • Allergen Designation:None
      • Protein Family:EF hand calcium binding proteins, Pfam PF00036; efhand.
      • Sequence Known?:Yes
      • Allergen accession No.s:http://us.expasy.org/cgi-bin/niceprot.pl?P59747 (Scomber japonicus)
      • 3D Structure Accession No.:N/A
      • Calculated Masses:11414 Da
      • Experimental Masses:11 kDa
      • Oligomeric Masses:Not known
      • Allergen epitopes:Not known. Bugajska-Schretter et al. (1998) [1318] show that IgE binding to carp beta-parvalbumin is very much stronger in the presense of calcium, when the protein is in its native folded form, suggesting that the epitopes are primarily conformational.
      • Allergen stability:
        Process, chemical, enzymatic:        Most parvalbumins quickly refold in the presence of calcium and thus allergenicity survives cooking. The purification of mackerel parvalbumins can include a heat treatment using a boiling water bath for 20 minutes without loss of IgE binding (see below).
      • Nature of main cross-reacting proteins:

        Hansen et al (1997) [1295] showed that there was IgE cross-reactivity between cod, plaice, herring and mackerel in their 8 patients using skin prick, histamine release and inhibition of IgE binding. This was shown by immunoblotting to be due to the parvalbumins related to Gad c 1 of cod. Similarly, Hamada et al. (2003) [1395] found that IgE from 4/5 patients reacting to salmon, cod, sardine and tuna also bound to the parvalbumins from the 3 species of mackerel. IgE from the fifth patient's sera was found to bind to collagen. Hamada et al (2004) [1392] tested the effectiveness of inhibition of IgE binding of natural and recombinant mackerel parvalbumin against purified parvalbumins from Japanese eel, horse mackerel, red sea bream, skipjack, bigeye tuna and Japanese flounder. They concluded that there was significant cross-reactivity and that the recombinant mackerel parvalbumin could be used to diagnose fish-allergy.

      • Allergen properties & biological function:Parvalbumins control the flow of calcium from troponin C back to membrane bound pumps after a muscle contraction. Each parvalbumin can bind two calcium or (with lower affinity) magnesium ions.
      • Allergen purification:

        Parvalbumin was purified from the white muscle of three species of mackerel (Scomber japonicus, S. australasicus and S. scombrus) by gel filtration on Sephadex G-75 and reverse-phase HPLC on TSKgel ODS-120T, essentially as described for horse mackerel (Shiomi et al, 1998 [1583]). Purified preparations from each of the three species gave a single band of about 11 kDa (Hamada et al. 2003 [1395]).

        Parvalbumin was also purified from the white muscle of the more distantly related horse mackerel (Trachurus novaezelandiae). An extract was made by homogenizing white muscle with 4 volumes of 0.01 M phosphate buffer, pH 7.0. The extract was centrifuged at 18,800 x g for 20 minutes. The supernatant was heated in a boiling water bath for 20 minute and centrifuged again. After dialysis against water (Spectra/Por 6 membrane, cut-off 3500 Da) and concentration with a rotary evaporator, the supernatant was purified by gel filtration on a Sephadex G-75 column (2.5 x 90 cm) equilibrated with PBS, pH 7.0, and eluted at 30 ml/h. Allergen containing fractions were combined and applied to reverse-phase HPLC on a TSKgel ODS-120T colun (0.46 x 25 cm). Fractions were eluted at 1 ml/h. with a gradient of acetonitrile in 0.1% trifluoroacetic acid. Parvalbumin was eluted as a single peak after 6 small peaks. The yield was 31 mg from 78 g of horse mackerel muscle and this gave a single band corresponding to a molecular weight of 10,500 by SDS-PAGE, regardless of the presence or absence of a reducing agent (Shiomi et al, 1998 [1583]).

        Hamada et al (2004) [1392] expressed recombinant pacific mackerel, Scomber japonicus, as a 38 kDa GST-fusion protein in E. coli using the pGEX-6p-3 system. This was specifically bound on a glutathione-Sepharose 4B column and cleaved with PreScission Protease on the column. The parvalbumin was eluted from the column to give approximately 24 mg/l of parvalbumin giving a single band at 12 kDa on SDS-PAGE.

      • Other biochemical information:

        The sequence P59747 from mackerel is most similar to Q90YK7  from Alaska pollack with 89/108 residues identical. Thus it is a member of the group of beta-parvalbumin sequences including  Q90YK7 (Alaska pollack), Q8UUS3 and Q8UUS2 (carp), Q91482 (salmon) and Q90YK9 (cod) which are more than 70% identical in sequence. These sequences are 65-67% identical in sequence with members of a second group including Q90YK8 (Alaska pollack), Q91483 (salmon) and Q90YL0 (cod). However, Hamada et al. (2003) [1395] note that only one parvalbumin is present in mackerel at more than trace concentration.

        3-D structures are available of beta-parvalbumins from carp, Cyprinus carpio, 4CPV, whiting, Merlangius merlangus, 1A75, silver hake, Merluccius Bilinearis, 1BU3, and pike, Esox lucius, 1PAL.

        Hamada et al (2004) [1392] purified a recombinant parvalbumin with an additional N-terminal sequence Gly-Pro-Leu-Gly-Ser, an unblocked N-terminus and no glycosylation. They argue that its similar IgE binding properties show that the N-terminus and glycosylation are not involved in IgE binding.

        The 13 kDa allergen identified by Bernhisel-Broadbent et al. (1992) [1397] (see immunoblotting) almost certainly corresponds to the mackerel parvalbumin with the 11-13 kDa range of observed molecular mass being due to different SDS-PAGE systems.

      References (5)

      • Hamada Y, Tanaka H, Sato A, Ishizaki S, Nagashima Y, Shiomi K.
        Expression and evaluation of IgE-binding capacity of recombinant Pacific mackerel parvalbumin.
        Allergology International 53(3), 271-278.. 2004
        PUBMEDID:
      • Hamada Y, Tanaka H, Ishizaki S, Ishida M, Nagashima Y, Shiomi K.
        Purification, reactivity with IgE and cDNA cloning of parvalbumin as the major allergen of mackerels.
        Food Chem Toxicol. 41(8):1149-1156.. 2003
        PUBMEDID: 12842183
      • Bugajska-Schretter A, Elfman L, Fuchs T, Kapiotis S, Rumpold H, Valenta R, Spitzauer S.
        Parvalbumin, a cross-reactive fish allergen, contains IgE-binding epitopes sensitive to periodate treatment and Ca2+ depletion.
        J Allergy Clin Immunol. 101(1 Pt 1):67-74.. 1998
        PUBMEDID: 9449503
      • Hansen TK, Bindslev-Jensen C, Skov PS, Poulsen LK.
        Codfish allergy in adults: IgE cross-reactivity among fish species.
        Ann Allergy Asthma Immunol. 78(2):187-194.. 1997
        PUBMEDID: 9048527
      • Shiomi K; Hayashi S; Ishikawa M; Shimakura K; Nagashima Y.
        Identification of parvalbumin as an allergen in horse mackerel muscle
        FISHERIES SCIENCE 64, Iss 2, pp 300-304. 1998
        PUBMEDID: