Dear Editor,
The prevalence of fish allergy in the general population is 0.1%–3%.
1 Bleak (
Alburnus alburnus) is a river fish belonging to the
Cyprinidae family (
Fig. 1).
2 Different fish-related panallergens have been described.
1, 3 and 4 We report the first case of allergy to bleak where a panallergen was the sole trigger.
Fig. 1.
Bleak (Alburnus alburnus) of 15 cm in length.
We present the case of a 69-year-old non-atopic woman who suffered from edema of the tongue, uvular edema, generalized pruritic erythema and rapidly progressive dyspnea immediately after eating one piece of fried bleak. No other family member who ate the same fish had similar symptoms. One month before, she presented generalized urticaria after eating this fish previously well tolerated. Currently, she completely avoids fish and seafood. An allergy work-up was performed.
Skin-prick-prick (SPP) tests were positive (papule ≥3 mm than negative control) to river (bleak, pike, barbel, carp, trout) and sea (hake, cod, sardine, salmon) fish; and negative to anchovy, white tuna and red tuna. Skin-prick-tests (SPT) with negative (50% glycerinated saline) and positive (histamine, 10 mg/mL) controls were performed (BIAL-Arístegui, Bilbao, Spain). SPT was positive to extracts of bleak (body and head), carp, barbel, pike, hake, cod, sardine and salmon; and negative to sole, anchovy, tuna, clam, oyster, squid, prawn and Anisakis simplex. Protein extracts from pike, barbel and carp (bodies), and bleak (body and head) were prepared by homogenization in phosphate-buffered-saline, dialyzation and lyophilization.
Serum total IgE, specific IgE and baseline tryptase levels were measured by ImmunoCAP™ (ThermoFisher, Massachusetts, USA). Serum specific IgE levels against bleak body and head were measured with the enzyme allergosorbent technique (Specific IgE EIA kit, HYTEC, HYCOR Biomedical Ltd., USA). Two parvalbumin-dependent anaphylaxis patients served as positive blotting-assay controls (patient #1: serum specific IgE against Gad c 1 of 1.08 kUA/L; patient #2 of 38.40 kUA/L) (negative <0.35 kUA/L). Serum total IgE was 153 UI/mL (normal <100). Specific IgE against A. simplex was negative (<0.10 kUA/L) and positive to cod (1.34 kUA/L) and salmon (0.70 kUA/L). In contrast, specific IgE against different fish (trout, tilapia, grayling, bullhead, zander, sardine, anchovy, hake, tuna) and seafood (shrimp, mussel, squid) were negative (between 0.14 and 0.04 kUA/L) as well as against the parvalbumins Gad c 1 (0.06 kUA/L) and Cyp c 1 (0.12 kUA/L) and tropomyosinDer p 10 (<0.10 kUA/L). Serum baseline tryptase levels were of 3.6 and 4.1 μg/L (normal <11.4). Specific IgE levels to body and head bleak extracts were <0.35 kUA/L but higher than the value obtained with a control serum (pool of sera from non-atopic subjects), so both values were between 0.35 and 0 kUA/L.
Therefore, to ascertain whether bleak was the real cause of this anaphylactic reaction, bleak extracts (body and head) were studied by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions (2-mercaptoethanol),
5 transferred onto polyvinylidene difluoride membrane filters (Millipore Corp., Bedford, Massachusetts, USA), and incubated with patient serum. Two IgE-binding bands of 55 kDa and less than 14 kDa were revealed in both bleak extracts (results not shown). An IgE-Immunoblotting assay after tricine-SDS-PAGE analysis with bleak body extract was performed as previously described.
6 The membrane was incubated with patient serum and with a rabbit anti-serum against sardine parvalbumin. The same IgE-binding band profile was revealed with both sera. This result led us to suppose that all the IgE-binding bands detected were different aggregation states of the bleak parvalbumin, and the 11 kDa-IgE-binding band was the monomeric state of this protein (
Fig. 2-I). Furthermore, the extracts of various river fish (pike, carp and barbel) were studied by the SDS-PAGE Immunoblotting method as described by Laemnli using patient serum and the sera from the two parvalbumin-allergic patients.
5 The IgE-binding band profile was the same with the three sera, and the parvalbumin protein appeared as a protein with a molecular mass smaller than 14 kDa. The other higher bands observed are the different aggregation states of the parvalbumin as was detected by tricine-SDS-PAGE IgE-Immunoblotting (
Fig. 2-I). SDS-PAGE Immunoblotting inhibition assays using extracts from pike, carp and barbel body (solid phases) showed that both bleak extracts (body and head) as well as carp, pike and barbel bodies were able to produce a total IgE binding inhibition on proteins from pike, carp and barbel extracts (
Fig. 2-II). Finally, in order to confirm a clinical monosensitivity to bleak and/or to offer a safe alternative fish diet, we performed an oral food challenge (OFC) with canned tuna (negative specific IgE, SPT and SPP), raw red tuna (negative SPP) and anchovy (negative specific IgE, SPT and SPP) in a very cautious way as previously described.
7 and 8 Our patient tolerated canned tuna and raw red tuna (both fish with no detected parvalbumin/g of fish),
1but not anchovy. Subsequently, no OFC with other fish was performed. She also tolerated squid, shrimp and mussel.
Fig. 2.
I) SDS-PAGE Immunoblotting. A) Extract from raw bleak body; B) Extract from raw barbel body. Lane P1, patient's serum; lane C, control serum (pool of sera from non-atopic subjects); lane S, rabbit anti-serum against sardine parvalbumin; lane C1, unimmunized rabbit serum; lane M, molecular mass marker; lane P2and P3, sera from control parvalbumin-allergic patients. II) SDS-PAGE Immunoblotting-inhibition showing the obtained results with barbel body extract as solid phase; the results were similar with pike and carp as solid phase. Solid phase: Extract from raw barbel body. Lane C, control serum (pool of sera from non-atopic subjects); lanes 1–6, patient's serum pre-incubated with raw barbel body extract (1), raw bleak body extract (2), raw bleak head extract (3), raw pike body extract (4), raw carp body extract (5), and lamb extract (6); lane M, molecular mass marker.
Spain is the country with the third highest fish consumption after Japan and Portugal.
9Currently, part of the Spanish population consumes river non-marketed fish perhaps with the intention of avoiding
Anisakis-parasited fish, but overlooking the risk of coming into contact with other allergenic fish proteins. Fish parvalbumins are proteins of 9–11 kDa which show a high degree of IgE cross-reactivity between them, including parvalbumin from river fish.
1,3 and 4 We highlight the negative specific IgE values detected in our patient's serum against the commercially available parvalbumins,
Gad c 1 and
Cyp c 1 (parvalbumin from a river fish) (ImmunoCAP system). Thus, our patient could have been diagnosed with an allergy exclusive to bleak and a life-threatening episode after eating other fish could have occurred.
In conclusion, as far as we know, this is the first published case of allergy to bleak. The parvalbumin proved to be the allergen even though a negative specific IgE value to parvalbumins was detected by means of conventional analyses, which are used for diagnosing parvalbumin-induced fish allergies. In this case, the clinical significance of the allergenic cross-reactivity between bleak parvalbumin and parvalbumin from river and sea fish was demonstrated by serologic tests and OFC.
Conflicts of interest
BB is an employee of BIAL-Arístegui. The rest of the authors have no conflict of interest.
Acknowledgments
This work was partially supported by a grant from
Comunidad de Madrid MITIC-CM(
S2010/BMD-2502). The work did not receive any grant, honorary, fees from BIAL-Arístegui, the employer of the author BB.
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Peer review under responsibility of Japanese Society of Allergology.
Corresponding author. Servicio de Enfermedades del Sistema Inmune–Alergia, Hospital Universitario Príncipe de Asturias, Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Carretera Madrid-Barcelona Km 33.600, Alcalá de Henares, Madrid, Spain.
Author(s): José Barbarroja-Escudero, María-José Sánchez-González, Mercedes Rodríguez-Rodríguez, Darío Antolín-Amérigo, Borja Bartolomé, Melchor Alvarez-Mon
