Allergic Reaction To Fish

Fish allergy has played a primary role in the study of adverse reactions to food as a fish study has shown for the first time the presence of a serum related to this allergy and that this factor (then identified in IgE) could be passively transferred to a normal subject. It was the so-called Prausnitz and Künstner test (P-K test). In 1921, two German physicians Otto Carl W. Prausnitz and Heinz Künstner performed the following experiment: 24 hours after injecting intradermally a small amount of Künstner’s whey, which was allergic to fish, in the skin of Prausnitz, in that same area skin was injected with an allergenic fish extract with within a few minutes of erythemato-pomphoid reaction.

Fish is a nutritional resource of great importance in many parts of the Earth and also provides a wide range of derivatives such as those derived directly from the meat, the surimi (which in Japanese means “minced fish”), a term used to indicate a product made of Teragra chalkfish pulp, a cod called Pollack of Alaska, usually packed in orange and white colored cylinders formed at various layers of leaf (eg, caviar), or their skin (eg gelatine), or their liver (eg oil), and others yet.

Fish is a frequent cause of food allergy. Such allergy can be favored by local eating habits, such as in countries where fisheries are the largest, such as Japan, Spain, Scandinavia; or atopic soil, often accompanied by atopic eczema; or sometimes it may appear when the introduction of fish begins in the process of child nutrition differentiation.
Fish in most of Europe is the third most frequent allergen after egg and cow’s milk.

In Italy, a study on the equilibrium in the pediatric population showed that the fish was fourth in milk, eggs and seeds.

There are many causes that come into contact with fish. This contact may also be unintentional or misunderstood as fish is an ingredient of many recipes: for example, Fish hydrolysates are often used for both nutritional and gourmet purposes.

Allergic reactions to fish ingestion are numerous. It should be borne in mind that some people may have abnormal sensations, reacting to extremely small exposures of allergenic proteins. Some authors estimate the proportion of fish allergic to about 10%, which also shows reactions to baking vapors and / or only skin contact with fish.
Professional pathologies are also possible from fish allergen reactions.

General information about allergens

Cod parvalbumin was one of the first allergens to be purified. It was subsequently seen that paravalbumines are the main allergen of fish in general (over cod, carp, salmon, tuna, thistle, and other bone or teleostasis fish)

The parvalbumin content however varies from one fish to the other, higher towards the head than the tail, higher in white meat than in red meat.

Even homology between comparable parvalbumins (in most fish is beta-parvalbumine) is not as strong as eg. the one between the crustacean tropomyosin. In fact, for example Gad c 1 and Gad m 1, although coming from two neighboring cod species, have only about 65% identity.

Cartilage fish (races, torpedoes, trigonites, eagles, mantras, chimeras and sharks) have another type of parvalbumin, alpha-parvalbumine; these show a moderate homology with beta-parvalbumines present in bone fish, such as cod, carp, tuna, salmon, etc. (eg 50-55% with Cyp c 1 beta-parvalbumin of carp). In general these fish have a minor allergenicity.

All of these aspects could affect the in vitro reactivity and the allergenicity of the various fish.

However, the fish contain only one type of allergen.

Many blots show a multiple reactivity for IgEs, so with bands with a molecular weight greater than 12-13 kDa referring to parvalbumin.

The presence of an aldehyde phosphate-dehydrogenase in various patients has been demonstrated, as well as a tri-phosphate isomerase.

IgE reactivity was demonstrated only for aldehyde phosphate dehydrogenase in cod.

Recently, they have been identified and analyzed in a carp (Megalobrama amblycehala), a well-consumed freshwater fish in China, an enolase and a creatinine kinase, in 11 allergic patients. They show no cross-reactivity with parvalbumin. There may be two new allergens.

Some bands may depend on dimers, triads or tetramers, highlighted for Atlantic cod parvalbumin, or from the manipulations to which these fish are subjected for marketing.

Collagen is also an allergen present in fish. Hamada reports an IgE-responsiveness to tuna collagen in fish allergic patients.

This collagen is cross-reactive with the collagen of other fish.

However, the importance of collagen in fish allergy is little known.

Fish collagen is used to prepare jelly, which may highlight some allergenicity.

Polarity or monoreactivity: the aid of diagnostics

In theory, an allergic patient to a fish species reacts (or is at risk of reacting) to other fish species for cross-reactivity among the main fish allergens, parvalbumines.

In fact, only about half of those who are allergic to a fish would be allergic to another or to other fish.

There are also numerous cases of a single allergy to a specific species of fish. One can think that these isolated allergens represent a specific susceptibility of the patients to that or that other protein present in that fish or another.

In medical literature, there are several studies that have studied this cross-reactivity with a response to multi-reattività and multi-activity.

The analysis of these jobs is complex because of the wide variety of species consumed, often regional; for the great heterogeneity of the methods of diagnosis used, whether they are skin tests or in vitro tests.

So we can have two situations

  • An allergic patient to a specific species of fish and not other fish
  • An allergic person to a fish that may have a 50% chance of being allergic to one or other fish.

In the first situation, the behavior is simple and clear.

In the second situation we do not generally need an oral provocation test as we have available, after discarding a non-allergic cause, skin tests and the determination of specific IgEs that can be extended to various species, which would confirm or not the multi-reactivity crusade.

Raw products are used for both skin and in vitro tests.

However, with the performance of these tests, we may have some discrepancies:

  1. Even though parvalbumin is not destroyed by cooking, it is possible that the skin test is negative in a subject that clinically responds to the same fish when cooked;
  2. There is a discrepancy between skin tests and in vitro tests for differences between the extracts used by the industry obtained with more or less specific media.

What role do recombinant allergens cause in fish allergy?

Two recombinant allergens were introduced: first the beta-parvalbumin of carp rCyp c 1 and then the cod of rGad c 1 were introduced. Other recombinants showed their feasibility.

Are these tests more advantageous than those based on extracts?

The answer is quite blurred:

  • rGad c 1 could explore a slightly different reactivity to the F3 test in immunoCAP (cod), since the former is derived from Gadus callarias, while the classic CAP cod comes from a Gadus morhua extract. Now the homology between the beta-parvalbumines of the two species and, unexpectedly, relatively weak: 64-67% between Gad c 1 and Gad m1, depending on the isoforms of these allergens
  • Equally rGad c 1 does not overlap rCyp c 1 (sequential identity of 68%), and differences are clearly observed at level 2 of the 3 epitopes between these two allergens. So in the same patient a negative test for one of the two recombinants might, by absurdity, be positive with each other;
  • It appears that the reactivity of the recombinants is more or less conditioned by the lack of natural ligand, calcium, which remains present when the allergen is obtained by purification from the natural product
  • There are no studies to ascertain whether rCyp c 1 or rGad c 1 have a good clinical relevance: rCyp c 1 has not been tested in skin tests and has received evidence of its allergenicity by releasing histamine, and it has not been studied that in a just patient; rGad c 1 was positive in a skin test in only 1 in 10 patients versus 9/10 for natural nGad c 1 allergen.

In conclusion, due to the high prevalence of parvalbumin responsiveness to fish allergic patients, the gains for rCyp c 1 and / or rGad c 1 are likely to be limited, in comparison with in vitro tests based on global extracts of fish.
For example, we list among the fish present in the immunoCAP Phadia system as well as the recombinants mentioned above

  • f313 = anchovy or alice (Anchovy)
  • f50 = Japanese mackerel (Chub mackerei)
  • f3 = cod, cod, stockfish (Cod)
  • f264 = anguilla (Eel)
  • f410 = collects various species of cernie (Grouper)
  • f307 = nasello (Hake)
  • f205 = herring (Herring)
  • f206 = common mackerel (Mackerel)
  • f41 = salmon (Salmo salar)
  • f308 = sardine (Sardine)
  • f337 = common sole (sun)
  • f312 = swordfish (Swordfish)
  • f40 = tuna, yellow fin tuna (Tuna / Yellow fin)

In cases of obvious clinical doubt and criticalness, deeper into simple or double-blind oral provocation tests.

General information on the influence of heat (cooking) and digestion on fish

Allergic Reaction To FishCooking changes the protein profile of fish: thicker molecular weights appear often.

Parvalbumins are thermostable, even in the absence of their natural ligand, calcium. Their allergenicity is a priori conserved, although comparisons before and after cooking with oral provocation tests have not been carried out so far.

Fish cooking at 100 ° C is frequent, but can also reach higher temperatures.
The fate of allergenicity after frying has not been well studied: Chatteriee observes varying results depending on the patient. In another work, IgE-reactivity was not changed after frying (or after boiling)

Conservation processes seem to induce epitope modifications and may lead to a reduction in IgE-responsiveness, at least in vitro (see tuna file)

The fish is generally smoked hot. Temperatures are, however, modest (about 70 ° C). The evolution of allergenicity due to smoking, salting and / or drying has been studied are in vitro: Sometimes the parvalbumin to the blot has increased, sometimes decreased, depending on the processes and / or type of fish. Bands of high molecular weight may appear. Moving at the level of clinical risk these modifications are not possible.

IgE was studied after the fish had been marinated in an alkaline medium: this fish whose meat is strongly transformed and corresponds to the original Scandinavian recipe of “lutefisk” exhibited an increased in vitro IgE-reactivity.

It is believed that digestion does not alter the allergenicity of parvalbumin, and therefore also that of fish. Parvalbumines are then considered as complete allergens, capable of inducing the synthesis of IgE, and this involves the stability of the allergy to fish.
Yet a raw cod extract is completely degraded in less than a minute in in vitro simulated gastric digestion at pH 1.2. Untersmayr has shown that pH plays a key role in the efficacy of peptic digestion of parvalbumines: in fact, to induce a positivity to a Oral provocation at a pH of 3 requires amounts of 10 to 30 times less of parvalbumin than an oral provocation test at pH 2.

It is evident that the real conditions are important to consider and the complexity of the food bolus is known to be more random than obtaining a very low pH.

Finally, Untersmayr underlines the damage that anti-H2 medicines represent to fish-sensitized patients, as the use of anxiety by increasing gastric pH can lead to incomplete digestion and thus increase exposure to fish allergens.

Moreover cod proteins have been revealed in serum very soon after ingestion and this raises the hypothesis of pre-intestinal absorption.

Fish affecting fisheries, conservation and processing

Various work has examined the evolution of fish protein in these situations

  • The enormous overpopulation of fish in a restricted area before harvesting in aquaculture causes a change in the protein profile:
  • A myofibril and protein proteolysis of the matrix occurs in the post-mortem; however, pre- and post-rigigor mortis blots seem similar. The natural transformation of fish meat could be sought, such as the gelling of raw fish in the recipes of Asian cuisine (eg kameboko)
  • Preservation in ice modifies the reactivity of cod IgE: that of parvbumin Gad c 1 decreases, but overall, IgE reactivity has increased
  • Freezing decreases the band corresponding to the aldehyde-phosphate dehydrogenase in the cod. During this mode of conservation for a lipid oxidation phenomenon, protein carbonylation may occur. These freezing studies have not been studied on the level of reactivity to IgE.

The agri-food industry has tried to use fish inventories by making croquettes. Microbial transglutaminase (mTG), associated with the addition of soy protein, seems to give good technological results. But the result of this treatment from the immunological point of view has not been studied. Now transglutaminase, which is a kind of organic glue, creates a very solid lattice between proteins whose bonds are highly resistant to digestion. Likewise, if mTG does not seem to possess an allergenicity in itself, it may be judicious to check the effects on the allergenicity of the products on which this enzyme is made.

Is Crushed Allergy to Fish and Crustaceans or Mollusks?

It is not unusual to observe an allergy to fish accompanying clinical reactions to contact with sea shellfish and / or sea shells. The role of local eating habits can partly explain this concomitance.

But is there a molecular bond between these molecular reactions, a link that would justify the global evolution of sea products?

To date, no cross-reactivity between fish allergen and crustacean or shellfish allergen has been shown. The taxonomic distance between these living species seems too large to allow an expression of epitopic similarity. So the salmon tropomyosin has only 54% identity with that of the shrimp pen at 1.

Thus a simultaneous allergy to these different sea products is rather the result of an atopic soil favorable to independent and cumulative sensitization.

Fish Eggs

Eggs of various fish are eaten, the most famous ones come from sturgeon (Acipenser sturio): caviar. The term “caviar” is protected and therefore can not be used for eggs of other fish.
Some cases of allergy have been reported to these eggs: salmon, trout, lavarello, beluga caviar.

In general these allergies are clinically limited to one type of egg, and are not accompanied by allergy to the same fish.

Cross-reactivity tests were carried out. The results are quite different between different fish eggs and between them and fish extracts. The number of remarks remains very limited and it is therefore difficult to draw conclusions.

It is also possible to exclude the possibility of egg contamination by fish protein.

The allergens involved in fish-fish reactions seem to correspond to vitellogenins, high molecular weight proteins present in eggs along with other proteins such as lipovellines and fosvit, thus also referring to egg yolk protein.
Authors who have tested cross-reactivity between fish eggs and egg yolks have found negative results.

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