Allergy information for: Cod (Gadus morhua )

Clinical History

• Number of Studies:>20
• Number of Patients:>50
• Symptoms:

  There are very many articles describing "fish" allergy. The cod entry contains data from some of these as well as articles where cod is explicitly mentioned. Selected key articles on cod or fish allergy are summarised below.

  All 30 patients of Hansen et al. (2004) [1297] reported oral allergy syndrome on consuming fish. Reported cutaneous symptoms included angioedema in 11 patients, urticaria in 14, eczema in 13, erythema in 6 and conjunctivitis in 2. Respiratory symptoms included asthma in 16, rhinoconjunctivitis in 13 and oropharyngeal swelling in 1 patient. Gastrointestinal symptoms (nausea, vomiting, diarrhoea, abdominal pain) were reported by 13 patients. The age at onset of fish allergy varied from <1 year to 20 years old, with most individual's allergy developing in childhood.

  Symptoms of fish allergy may only require a low dose of allergen. There is a report of a 2 year old girl suffering facial urticaria and angioedema after a kiss (Monti et al. 2003 [1387]).

  Sakaguchi et al. (2000) [1394] report the symptoms of 12 patients, age 1 to 40 years, with allergy to various fish as urticaria in 10/12 with wheezing and itching in the mouth respectively in the remaining individuals. Five of the patients with urticaria suffered additional symptoms of angioedema, cough, cough and stomach ache, cough with wheezing and vomiting, and hypotension, airway obstruction and diarrhea. 15 additional patients with atopic dermatitis, age 8 to 45 years, had specific IgE to fish.

Skin Prick Test

• Number of Studies:>20
• Food/Type of allergen:

  Sten et al (2004) [1386] used commercial, glycerinated allergen of codfish for comparison with freshly thawed ocean pout, eelpout and eel.

  Hansen et al. (2004) [1297] used commercial, glycerinated allergen of codfish, 1:20 w/v (Soluprick, ALK-Abelló) and fish gelatin diluted in saline 0.9% (0.5 g/ml). The gelatine was prepared from the skins of codfish by acid extraction (type A gelatine, Mr 60,000).

  Hansen et al. (1997) [1295] used comercial extracts.

• Protocol: (controls, definition of positive etc)Hansen et al. (1997) [1295], Sten et al (2004) [1386] and Hansen et al. (2004) [1297] considered as positive a weal with net diameter 3 mm larger than that of the negative control (a diluent of glycerol/NaCl).
• Number of Patients:

  Hansen et al. (2004) [1297] tested 30 clinically allergic patients with cod and fish gelatine.

  Sten et al (2004) [1386] tested 18 patients. One patient was not tested with raw fish because of their high IgE level and the severe reactions to SPT (swelling of arm and itching) seen with some patients (these may include some of those from Hansen et al, 2004 [1297]).

  Hansen et al. (1997) [1295] tested 8 DBPCFC positive patients and 30 controls (3 DBPCFC negative, 8 non-atopic, 7 with pollen allergy and 12 with atopic dermatitis).

• Summary of Results:

  Sten et al (2004) [1386] reported that all 18 SPTs with cod extract were positive and 17 of 18 patients reacted to all fish species with generally large weals.

  Hansen et al. (2004) [1297] report that all 30 patients gave positive SPT to cod extract and that 3/30 gave positive SPT to gelatine.

  Hansen et al. (1997) [1295] report that all 8 DBPCFC positive patients gave positive SPT with cod extract.

IgE assay (by RAST, CAP etc)

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

  Commercial extracts were used with CAP. Fish gelatine used by Sakaguchi et al. (2000) [1394] was prepared from different fish (eg, tuna, salmon, saurel, and mackerel) by 0.5 M acetic acid extraction and purified by differential salt precipitation.

  Hansen et al. (1996) [1296] and Hansen et al. (1997) [1295] prepared an extract from fresh raw cod.

• IgE protocol:

  Hansen et al. (2004) [1297], Sampson & Ho (1997) [652], Sampson (2001) [651], Sakaguchi et al. (2000) [1394], Bugajska-Schretter et al. (1998) [1318] and Dory et al. (1998) [1372] used CAP. Hansen et al. (1996) [1296] also compared Phadebas, CAP, Magic Lite and Maxisorp.

  Sten et al (2004) [1386] used direct Maxisorp-RAST and RAST inhibition.

  Sten et al (2004) [1386], Hansen et al. (2004) [1297] and Hansen et al. (1996) [1296] also used a histamine release test.

  Sakaguchi et al. (2000) [1394] used ELISA for gelatine specific IgE.

• Number of Patients:

  Untersmayr et al. (2005) [1363] used sera from 3 patients.

  Sten et al (2004) [1386] used sera from 18 patients.

  Hansen et al (2004) [1297] used sera from 30 clinically fish allergic patients.

  Sakaguchi et al. (2000) [1394] used sera from 12 fish allergic patients and 65 patients with atopic dermatitis. The 15 with IgE to fish were tested for IgE to fish gelatine.

  Bugajska-Schretter et al. (1998) [1318] tested sera from 30 patients

  Dory et al. (1998) [1372] used sera from 12 patients.

  Hansen et al. (1996) [1296] and Hansen et al. (1997) [1295] used sera from 8 DBPCFC positive patients and 30 codfish tolerant controls (3 DBPCFC negative, 8 non-atopic, 7 with pollen allergy and 12 with atopic dermatitis).

• Summary of Results:

  Hansen et al. (2004) [1297] report that sera from all 30 patients reacted with cod extract (range 0.36–477 kUA/l; mean 33.65 kUA/l).

  Sten et al (2004) [1386] reported that all 18 sera reacted with all 4 fish extracts. The amount of specific IgE were in all cases higher for codfish compared with the other fish species. However, all extracts were able, with dose-dependency, to inhibit the binding to codfish and ocean pout for all sera at least to some extent.

  Sampson & Ho (1997) [652] and Sampson (2001) [651] sugest that a specific IgE level predicting clinical fish allergy with 95% confidence was 20 kU_A/L. The sensitivity was 25% and specificity 100%. Challenge was recommended for IgE levels 0.35 - 20.0 kU_A/L.

  Sakaguchi et al. (2000) [1394] report specific IgE levels of 0.5 - 18.9 kU/l for cod in 5/12 fish allergic patients and 0.45 - 97.1 kU/l for all the fish tested (cod, mackerel, salmon, saurel and tuna) in the 12 patients. 7 of these patients had specific IgE to fish gelatine with 0.45 - 51.5 kU/l. 5 of these sera were tested with gelatines from different species and in general showed similar IgE binding. 15/65 patients with atopic dermatitis showed 0.48 - 20.2 kU/l for either cod or tuna. 10 of these patients had 0.5 - 49.9 kU/l specific IgE to fish gelatine.

  Bugajska-Schretter et al. (1998) [1318] report cod specific IgE levels of 1.4 - 42.2 kU/l (class 2 to 4). Salmon and tuna specific IgE were also measured and were class 1 to 4.

  Dory et al. (1998) [1372] report cod specific IgE levels of 1.9 - 92.9 kU/l (class 2 to 4).

  Hansen et al (1997) [1295] reported that sera from 8 codfish allergic patients had specific IgE to other fish species, and in inhibition-studies extracts of herring, mackerel, and plaice were capable of inhibiting reactivity to codfish in a varying degree.

  Hansen et al. (1996) [1296] report that a cod specific IgE level of 0.67 kU/l in CAP (compared to 0.35 kU/l) was diagnostic of food allergy in all 8 cod allergics but gave fewer false positives in the controls. Similar results were seen using Magic Lite and Phadebas. Also an extract from fresh fish improved accuracy 

Immunoblotting

• Immunoblotting separation:

  Untersmayr et al. (2005) [1363] followed the methods of Lammeli (1970) [948], implying that the samples were reduced although this is not explicitly stated.

  Sten et al (2004) [1386] used a 1.0 mm 16% separating gel with a 4% stacking gel. The samples were diluted in a reducing buffer and boiled before use.

  Bugajska-Schretter et al. (1998) [1318] used 12% separating gels with 5% stacking gels following Lammeli (1970) [948]. Extracts were heated at 95° C for 3 minutes. Approximately 100 µg of each fish extract were loaded per centimeter of gel.

  Galland et al. (1998) [1373] used stacking gels of 4% and separating gels of 12% acrylamide in 25 mM Tris–HCl (pH 8.3), 0.18 M glycine, 0.1% (w/v) SDS. Each sample contained 10 mM Tris–HCl (pH 8.0), 1 mM EDTA, 1% (w/v) SDS, 40 mM DTT, 10% (v/v) glycerol, 0.015% (w/v) bromophenol blue and was heated at 100°C for 3 min before loading.

  Dory et al. (1998) [1372] used 10-20% acrylamide separating gels.

  Hansen et al (1996) [1296] used 16 % separation gels with a 5 % stacking gel. Samples were diluted in a sample buffer containing 5 % mercaptoethanol and were boiled before use.

• Immunoblotting detection method:

  Untersmayr et al. (2005) [1363] blotted the separated proteins onto nitrocellulose by the method of Towbin. Blots were saturated with blocking buffer containing 0.5% (w/v) dried milk powder and incubated overnight at 4°C with sera from patients or healthy control subjects. Bound IgE antibodies were detected with iodine 125–labeled anti-human IgE antibodies (IBL, Hamburg, Germany) and visualized by means of autoradiography.

  Sten et al (2004) [1386] blotted the separated proteins onto a polyvinylidene fluoride (PVDF) membrane (Millipore, Bedford, MA) for 1.5h (I=1.0 mA/cm²). The membranes were blocked with tris buffered saline with 0.5% (v/v) Tween and 5% (w/v) BSA for 2 h at room temperature before incubating overnight at 4°C with the sera. For inhibition studies the sera were preincubated with extract (2 mg/ml) overnight. After washing, the membranes were incubated with anti-IgE horseradish peroxidase (HRP) (Dako A/S, Glostrup, Denmark) for 2 h and washed again. ECL Western blotting detection reagent (Amersham Pharmacia Biotech) was used as substrate to reveal IgE binding.

  Bugajska-Schretter et al. (1998) [1318] transferred the separated proteins onto nitrocellulose by the method of Towbin. The nitrocellulose was cut into strips and blocked with phosphate buffered saline, pH 7.5, with 0.5% (v/v) Tween 20. The strips were then incubated overnight at 4°C with patients sera diluted 1:10 (v/v) in blocking buffer. Strips were washed 3 times with blocking buffer and bound IgE were detected with ¹²⁵I anti-IgE and revealed with autoradiographic film with intensifying screens at -70°C for 24-72 hours.

  Galland et al. (1998) [1373] transferred proteins onto a nitrocellulose membrane. This was blocked with 0.3% (v/v) Tween 20 in 20 mM Tris–HCl buffer (pH 7.4), 0.15 M NaCl (TBS) and incubated with sera from cod allergic patients (diluted 1:10 (v/v) with 0.1% (v/v) Tween 20 in TBS) and then with ¹²⁵I anti-IgE (diluted 1:10 with 0.3% (v/v) Tween 20 in TBS). IgE binding was detected by exposure for 72 h on a phosphor screen.

  Hansen et al 1996 [1296] transferred proteins onto nitrocellulose paper which was cut into strips and blocked in TRIS-buffered saline with 3% (w/v) powdered milk and 1.5% (v/v) Tween 20 (blocking solution). Then incubated with sera (1:10 v/v) in blocking solution. Bound antigen specific IgE was detected by anti-IgE diluted 1:12 (v/v) in blocking solution. IgE binding was detected by exposure to hyperfilm (Amersham) for 3, 7, and 14 days.

• Immunoblotting results:

  Untersmayr et al. (2005) [1363] report strong IgE binding to a band at 11.5 kDa and some faint bands at higher molecular masses which are removed on digestion.

  Sten et al (2004) [1386] report that serum IgE from one individual bound only to a 40 kDa protein. 5 individuals had serum IgE which bound only to the 12 kDa allergen (Gad c 1).  The other sera contained IgE which bound to 3 or more proteins (i.e. at 12, 17, 40 and 55 kDa). Only 2 of 18 sera did not bind the 12 kDa allergen (Gad c 1). Codfish, ocean pout, eelpout or eel extracts all inhibited IgE binding.

  Bugajska-Schretter et al. (1998) [1318] report that 24/28 sera showed strong IgE binding by parvalbumin near 12 kDa. The remaining sera bound parvalbumin more weakly. 7 sera recognised proteins of 200, 100, 80, 66, 35, 30, 25, 20 and 15 kDa. Removal of calcium reduced binding to parvalbumin in most sera tested. 3 sera were used to show that cross-reactive allergens occurred in tuna, salmon, perch, carp and eel.

  Dory et al. (1998) [1372] report IgE binding to proteins of 12, 22, 30, 45, 60, 67, 104 and 130 kDa from crude cod extract. Further 18, 41 and 80 kDa bands appeared following storage of fish. All the proteins bound an anti-parvalbumin monoclonal antibody suggesting either aggregates of parvalbumin or cross-linking of parvalbumin with other proteins or the presense of larger parvalbumin homologues. 

  Hansen et al. (1996) [1296] report that sera from all 8 DBPCFC positive patients bound to the 12 kDa allergen. Some control subjects with atopic dermatitis bound higher molecular mass proteins.

Oral provocation

• Number of Studies:6-10
• Food used and oral provocation vehicle:

  Hansen et al. (1996) [1296] used fresh raw cod in concentrated blackcurrent juice (1:4 diluted with water).

  Hansen et al. (2004) [1297] used fish gelatine in concentrated blackcurrent juice, water and Elemental 028.

• Blind:Hansen et al. (1996) [1296], Sampson & Ho (1997) [652], Helbling et al. (1999) [1389], Sampson (2001) [651] and Hansen et al. (2004) [1297] used DBPCFC.
• Number of Patients:

  Hansen et al. (2004) [1297] challenged 30 cod allergic patients with fish gelatine.

  Helbling et al. (1999) [1389] challenged 9 fish allergic patients with catfish, cod and snapper.

  Sampson & Ho (1997) [652] challenged 20 patients with "fish". Sampson (2001) [651] challenged a further patient.

  Hansen et al. (1996) [1296] report 11 challenges on patients aged 21 to 31 years. Hansen & Bindslev-Jensen (1992) [1714] also challenged some of these patients.

• Dose response:Hansen et al. (1996) [1296] and Hansen & Bindslev-Jensen, 1992 [1714] gave doses of 5 μg. to 5g., with a total cumulative dose of 6.7g. The lowest dose to cause subjective symptoms was 6 mg. Objective symptoms occurred at 56 mg and higher doses.

  Hansen et al. (2004) [1297] gave doses of fish gelatine up to a cumulative dose of 14.61g.

• Symptoms:

  Hansen et al. (2004) [1297] report that only one of the 30 patients mentioned a mild subjective symptom of itching in throat following consumption of 7.61 g cumulative dose of gelatine. However, no further development of symptoms occurred following the final dose of gelatine.

  Helbling et al. (1999) [1389] report that 14/19 challenges (74%) gave an objective response following oral challenge. The most common sign observed was emesis (37%); the most prevalent subjective symptom reported was oral allergy syndrome (84%). Three subjects reacted to at least three fish species and one subject reacted to two fish species tested. In regard to the positive challenges, the predictive accuracy of skin prick test and RAST was 84% and 78%, respectively.

  Sampson & Ho (1997) [652] report that 11/20 patients gave positive oral challenges with fish, 10 having cutaneous symptoms, 7 gastrointestinal and 1 respiratory symptoms.

  Hansen et al. (1996) [1296] report that all 8 challenge positive patients reported oral itching, 2 also reporting nausea and 1 abdominal pain following consumption of fish. The objective symptoms observed were erythema in 4 patients, blisters in 4, angioedema in 3, oropharyngeal swelling in 2, asthma in 1 and vomiting in 1. 3 negative challenges were also reported but it was speculated that a dose above 6.7 g. might have produced symptoms. 7 of the 8 patients reported had previosly been challenged by a different protocol (Hansen & Bindslev-Jensen, 1992) [1714] and had reacted including a single patient who suffered anaphylaxis. 3 negative challenges were also reported by Hansen & Bindslev-Jensen (1992).

IgE cross-reactivity and Polysensitisation

Other Clinical information

Reviews (2)

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• 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:

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Biochemical Information for Gad c 1

• Allergen Name:Gad c 1
• Alternatve Allergen Names:Gad m 1, parvalbumin, Allergen M
• Allergen Designation:Major
• 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?Q90YK9

  http://us.expasy.org/cgi-bin/niceprot.pl?Q90YL0

• 3D Structure Accession No.:N/A
• Calculated Masses:11420 Da (Q90YK9 without N-terminal acetyl modification)
• Experimental Masses:12.5, 24, 38 and 51 kDa (Das Dores et al. 2002 [1368]).
• Oligomeric Masses:Monomers are the main species. 24 kDa Dimers, 38 kDa trimers and 51 kDa tetramers, possibly disulfide linked, have been reported by Das Dores et al (2002) [1368]. Oligomers are well established for distantly related parvalbumins.
• Allergen epitopes:

  Bugajska-Schretter et al. (1998) [1318] show that IgE binding 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.

  Elsayed et al. (1991) [1391] used synthetic peptides to determine that peptides corresponding to residues 33-44, 65-74 and 88-96 are IgE binding epitopes. The peptide corresponding to residues 49-64 was also allergenically/antigenically active. A peptide corresponding to residues 88-103 functioned as a monovalent hapten, blocking and not eliciting allergic reaction.

• Allergen stability:
  Process, chemical, enzymatic:Parvalbumins are stable and quickly refold in the presense of calcium. Thus the allergenic activity survives boiling or frying (Hansen et al. 1994 [1393]). They are relatively resistant to pepsin above pH 2.5 (Untersmayr et al. 2005) [1363].
• Nature of main cross-reacting proteins:

  Gad c 1 from cod is a beta-parvalbumin. IgE cross-reactivity between the parvalbumin allergens found in most fin fish (Bugajska-Schretter et al, 1998 [1318]; Helbling et al, 1999 [1389]; Sten et al, 2004 [1386]). Van Do et al (2005) [1792] used SPT and ELISA inhibition with 12 patients and their sera to characterize the cross-reactivities of native and some recombinant parvalbumins from 9 species (cod, Gadus morhua, Atlantic salmon, Salmo salar, Atlantic mackerel, Scomber scombrus, tuna, Thunus albacares, herring, Clupea harengus, wolffish, Anarhichas sp., halibut, Hippoglossus hippoglossus,  flounder, Platichthys flesus, and Alaska pollack, Theragra chalcogramma). Cross-reactivity was generally observed although some parvalbumins and extracts were poor inhibitors of IgE binding to cod for some sera i.e. 2/10 sera did not show inhibition by salmon parvalbumin (although surprisingly recombinant salmon parvalbumin caused inhibition).

  Hilger et al. (2004) [1365] and Hamada et al. (2004) [1586] show that there is also IgE cross-reactivity between fish and frog parvalbumin allergens.

• Allergen properties & biological function:Parvalbumins control calcium flow in the muscular sarcoplasm.
• Allergen purification:

  Recombinant cod parvalbumins were expressed with histidine tags in E. coli, using the vector pET-19b, and purified from soluble fractions. Parvalbumin with an N-terminal MGHHHHHHHHHHSSGHIDDDDKH tag (His₁₀-T1), containing a cleavage site for enterokinase to allow removal of the tag, gave a single symmetrical peak by HPLC. The yield of His₁₀-T1 was 1.8 mg/200 ml of bacterial culture (Van Do et al. 2003 [1367]).

• Other biochemical information:

  Das Dores et al. (2002) [1368] give a sequence with a single change (a deletion) relative to http://us.expasy.org/cgi-bin/niceprot.pl?Q90YK9 (Van Do et al. 2003 [1367]). They comment that the original Gad c 1 sequence, http://us.expasy.org/cgi-bin/niceprot.pl?P02622, derived from peptide sequencing is significantly different from the DNA derived sequences and from sequences from other fish.

  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. 

References (10)

• Van Do T, Hordvik I, Endresen C, Elsayed S.
  The major allergen (parvalbumin) of codfish is encoded by at least two isotypic genes: cDNA cloning, expression and antibody binding of the recombinant allergens.
  Mol Immunol. 39(10):595-602.. 2003
  PUBMEDID: 12431393
• Das Dores S, Chopin C, Villaume C, Fleurence J, Gueant JL.
  A new oligomeric parvalbumin allergen of Atlantic cod (Gad mI) encoded by a gene distinct from that of Gad cI.
  Allergy 57 Suppl 72:79-83.. 2002
  PUBMEDID: 12144561
• 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
• Elsayed S, Apold J, Holen E, Vik H, Florvaag E, Dybendal T.
  The structural requirements of epitopes with IgE binding capacity demonstrated by three major allergens from fish, egg and tree pollen.
  Scand J Clin Lab Invest Suppl. 204:17-31.. 1991
  PUBMEDID: 1710368
• Untersmayr E, Poulsen LK, Platzer MH, Pedersen MH, Boltz-Nitulescu G, Skov PS, Jensen-Jarolim E.
  The effects of gastric digestion on codfish allergenicity.
  J Allergy Clin Immunol. 115(2):377-382.. 2005
  PUBMEDID: 15696099
• Hansen TK, Stahl Skov P, Poulsen LK, Bindslev-Jensen C.
  Allergenic activity of processed fish.
  Clinical Immunology News Suppl. 2:445.. 1994
  PUBMEDID:
• 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:
• Hilger C, Thill L, Grigioni F, Lehners C, Falagiani P, Ferrara A, Romano C, Stevens W, Hentges F.
  IgE antibodies of fish allergic patients cross-react with frog parvalbumin.
  Allergy 59(6):653-660.. 2004
  PUBMEDID: 15147451
• Helbling A, Haydel R Jr, McCants ML, Musmand JJ, El-Dahr J, Lehrer SB.
  Fish allergy: is cross-reactivity among fish species relevant? Double-blind placebo-controlled food challenge studies of fish allergic adults.
  Ann Allergy Asthma Immunol. 83(6 Pt 1):517-523. . 1999
  PUBMEDID: 10619342
• Sten E, Hansen TK, Stahl Skov P, Andersen SB, Torp A, Bindslev-Jensen U, Bindslev-Jensen C, Poulsen LK.
  Cross-reactivity to eel, eelpout and ocean pout in codfish-allergic patients.
  Allergy 59(11):1173-1180.. 2004
  PUBMEDID: 15461598

Biochemical Information for Gelatine

• Allergen Name:Gelatine
• Alternatve Allergen Names:None
• Allergen Designation:None
• Protein Family:Gelatine is derived from denatured collagens.
• Sequence Known?:

  Mixture

• Allergen accession No.s:N/A
• 3D Structure Accession No.:N/A
• Calculated Masses:N/A
• Experimental Masses:60 kDa (average)
• Oligomeric Masses:Not known
• Allergen epitopes:Not known
• Allergen stability:
  Process, chemical, enzymatic:Gelatine is a denatured aggregate.
• Nature of main cross-reacting proteins:No IgE cross-reactivity between fish and bovine gelatine was observed by Sakaguchi et al. (2000) [1394].
• Allergen properties & biological function:Collagens are the major structural proteins of skin.
• Allergen purification:Fish gelatine used by Sakaguchi et al. (2000) [1394] was prepared by 0.5 M acetic acid extraction and purified by differential salt precipitation from heat treated fish skins.
• Other biochemical information:This entry for fish gelatine is included because IgE binding was reported by Sakaguchi et al. (2000) [1394] and SPT was observed in 3/30 patients (and histamine release in 7/30) by Hansen et al. (2004) [1297]. However, Hansen et al. have shown that it is unlikely to be a clinically important allergen.

References (2)

• Hansen TK, Poulsen LK, Stahl Skov P, Hefle SL, Hlywka JJ, Taylor SL, Bindslev-Jensen U, Bindslev-Jensen C.
  A randomized, double-blinded, placebo-controlled oral challenge study to evaluate the allergenicity of commercial, food-grade fish gelatin.
  Food Chem Toxicol. 42(12):2037-2044.. 2004
  PUBMEDID: 15500940
• Sakaguchi M, Toda M, Ebihara T, Irie S, Hori H, Imai A, Yanagida M, Miyazawa H, Ohsuna H, Ikezawa Z, Inouye S.
  IgE antibody to fish gelatin (type I collagen) in patients with fish allergy.
  J Allergy Clin Immunol. 106(3):579-584.. 2000
  PUBMEDID: 10984381