• fish; egg; food allergy; food allergen; IgE


  1. Top of page
  2. Abstract
  3. Allergenic sources
  4. Major allergens
  5. Interspecies cross-reactivity
  6. Conclusions
  7. References

Allergens from fish and egg belong to some of the most frequent causes of food allergic reactions reported in the literature. Egg allergens have been described in both white and yolk, and the egg white proteins ovomucoid, ovalbumin, ovotransferrin and lysozyme have been adopted in the allergen nomenclature as Gal d1–d4. The most reported allergen from egg yolk seems to be alpha-livitin. In fish, the dominating allergen is the homologues of Gad c1 from cod, formerly described as protein M. A close cross-reactivity exists within different species of fish between this calcium-binding protein family, denominated the parvalbumins. This cross-reactivity has been indicated to be of clinical relevance for several species, since patients with a positive double-blind, placebo-controlled food challenge to cod will also react with other fish species, such as herring, plaice and mackerel. In spite of the importance of these two allergen systems, only a few studies have been performed, and the scarcity of cloned allergens from both of the systems is emphasized.

Fish and egg together with milk and crustaceans represent the animal kingdom in the “big eight” group of food allergens, to which the majority of food allergic patients are believed to react. Fish allergy has played a prominent role in the history of allergy, it being a fish allergen with which Prausnitz & Küstner for the first time demonstrated the transferable serum factor (1) that was many years later to be identified as IgE. The major allergen from Cod, gad c1, previously known as Cod M, was also the first allergen for which the protein sequence was described (2). Despite the importance of these allergenic materials, recently much more attention has been directed to the study of food allergens of plant origin. In the present review we shall address some basic findings related to the allergen systems of fish and egg.

Allergenic sources

  1. Top of page
  2. Abstract
  3. Allergenic sources
  4. Major allergens
  5. Interspecies cross-reactivity
  6. Conclusions
  7. References

Hen's egg comprises about 8–11% shell, 56–61% white and 27–32% yolk (3). While the white may be considered essentially an aqueous protein solution (10% protein and 88% water), the yolk is composed of 50% water, 34% lipid and 16% protein, giving it quite different properties. Egg white has been considered the most important source of allergens, but IgE-binding allergens have also been described in the yolk, suggesting that both common and distinct allergenic molecules are present. Thus in a study of 11 patients with a history of egg allergy (8 DBPCFC+/3 DBPCFC−) all sera reacted positively to both white and yolk. Eight patients reacted equally or more strongly to white, and even though white and yolk could to some degree inhibit the IgE binding of the other, yolk could only be partly inhibited by white in eight sera (4).

Fish species are abundant and exist in multiple edible forms that are consumed in most countries of the world. Table 1 lists some of the species for which commercial diagnostic kits are available. Allergenic activity resides in the meat (muscle), but recently concern has been raised as to whether products such as fish gelatin, made from skin and bones, also contains allergenic activity in the form of collagens. This may present a problem since the fish gelatin is used in vaccines (5). An increasingly reported food allergic reaction is caused by the parasite Anisakis simplex, which may be found in fish. Since it is not a fish allergen, it will not be discussed further, but it is important to bear it in mind when allergic reactions are experienced after ingestion of fish.

Table 1.  Egg allergens. Diagnostic preparations and defined allergens (20, 21). Allergenic molecules with a name according to the IUIS nomeclature are shown in italics
F1Egg whiteGallus domesticus
F233OvomucoidGallus domesticusGal d128 kDa
F232OvalbuminGallus domesticusGal d244 kDa
F83-IIIConalbumin (Ag22), ovotransferrinGallus domesticusGal d378 kDa
F84-IVLysozymeGallus domesticusGal d414 kDa
F75Egg yolk (freeze-dried)Gallus domesticus
F245Whole eggGallus domesticus

Both fish and especially egg may be concealed in various forms of foods and a food allergic patient may not always know when he or she has actually been exposed to the allergens (6).

Major allergens

  1. Top of page
  2. Abstract
  3. Allergenic sources
  4. Major allergens
  5. Interspecies cross-reactivity
  6. Conclusions
  7. References

The most frequently reported allergens in egg are shown in Table 1. Even though ovalbumin is probably one of the most studied antigens in immunology (a contemporary search in Medline produced about 12 000 hits) it does not appear to be the most allergenic molecule in humans. Conalbumin (=ovotransferrin) and ovomucoid turned out to be the most frequent allergens when a population of 34 adults with a positive case history and/or a positive RAST to egg were tested with a battery of methods, such as western blot (reduced and unreduced), crossed radio-immuno-electrophoresis (CRIE) and dot-blots using the individual proteins. Using as the criterion the agreement between two or more of the four methods, the frequencies of reactivity were found to be 53% (ovotransferrin), 38% (ovomucoid), 32% (ovalbumin) and 15% (lysozyme) (7). Different reports have emerged on the relative importance of the various allergens in egg white. Some of the differences may be due to the studies of different populations, i.e. it is likely that the egg proteins are processed differently in the digestive system of infants and adults. It should also be mentioned, however, that a rigorous purification of the reagents may be necessary to obtain pure proteins, since commercial preparations of individual egg white proteins may be somewhat contaminated (8).

Table 2.  Fish allergens. Diagnostic preparations and defined allergens (20, 21). The allergenic molecule (gad c1) with a name according to the IUIS nomeclature is shown in italics. Some species may have more than one allergen code since various commercial preparations exist
F3Cod fish (muscle)Gadus morhua
F3-I Gadus callariasGad c1 (allergen M)12
F21HerringClupea harengus
F205HerringClupea harengus
F204TroutOncorhynchus mykiss (Salmo gairdnieri)
F40Tuna, Yellow Fin (fish muscle)Thunnus albacares
F41Salmon (Atlantic) (Muscle)Salmo salar
F50Chub mackerel (Fish muscle)Scomber japonicus
F206MackerelScomber scombrus
F55Eel (Muscle)Anguilla anguilla
F264Eel (Muscle)Anguilla anguilla
F56Sea perch
F60Jack Mackerel/scad (Muscle)
F61Sardine, Japanese PilchardSardina melanosticta
F308Sardine, Pilchard (Muscle)Sardina pilchardus
F254Plaice (Muscle)Pleuronectes platessa
F129SoleSolea solea
F303Halibut (Muscle)Hippoglossus hippoglossus
F307Hake (Muscle)Merluccius merluccius
F311Megrim/wiff (Muscle)Lepidorhombus whiffiagonis
F312Swordfish (Muscle)Xiphias gladius
F313AnchovyEngraulis encrasicolus

As previously mentioned, egg yolk may also act as an allergen, presumably due to α-livetin, which may be the most relevant allergen in the sensitization to egg proteins via the inhalation route (9, 10).

The dominant major allergen in codfish is gad c1, which seems to be extremely stable to thermal and proteolytic processes (11) – a factor undoubtedly contributing to the legendary results of Prausnitz & Küstner (1). Although other molecular weight species have been described as allergens in cod and other fish species, it seems that there is a quite strong correspondence between IgE reactivity to gad c1 and clinical reactivity to cod (12) and probably other species of fish (13, 14).

Interspecies cross-reactivity

  1. Top of page
  2. Abstract
  3. Allergenic sources
  4. Major allergens
  5. Interspecies cross-reactivity
  6. Conclusions
  7. References

The substantial clinical cross-reactivity between cod and other fish species (14) is paralleled by an IgE cross-sensitization between many fish species (13–16). In a recent study by Bugajska-Schretter and coworkers, a corresponding protein to gad c1, parvalbumin from carp, has been thoroughly examined (17). The investigators found that the protein was abundantly distributed in muscle and fiber cells, and by inhibition experiments it was demonstrated that the protein could inhibit 80–90% of the total IgE binding activity to extracts of cod fish, tuna, and salmon. The parvalbumins to which the carp protein and gad c1 belongs is a family of calcium binding proteins, which play an important part in muscle physiology. As demonstrated in Fig. 1, this structure is well conserved throughout the animal kingdom, but the homology decreases with decreasing zoological relationship. So far, no cross-reactivities have been described outside the fish species.


Figure 1. Relative homology between parvalbumins (Ca++ binding proteins) from different species including cod fish (gad c1).

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In terms of sensitization to egg, a single study has indicated that some patients may be allergic to eggs from duck and goose and yet be tolerant to hen's eggs (18). This lack of cross-reactivity between eggs from different birds remains to be confirmed on a larger material.


  1. Top of page
  2. Abstract
  3. Allergenic sources
  4. Major allergens
  5. Interspecies cross-reactivity
  6. Conclusions
  7. References

In spite of the well-established allergenicity of fish and egg, surprisingly few studies have been performed describing the individual allergens and, compared to plant-derived food allergens, many allergens in various fishes still need to be described and cloned. Due to the major efforts to characterize plant-derived food allergens, new hypotheses about the relationship between allergenicity and function have emerged (19). It will be interesting to see if the same principles can also be applied to animal-derived allergens such as fish and egg.


  1. Top of page
  2. Abstract
  3. Allergenic sources
  4. Major allergens
  5. Interspecies cross-reactivity
  6. Conclusions
  7. References
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