Summary

Allergen

The major allergen of common carp (Cyprinus carpio) is a parvalbumin protein known as Cyp c 1. This 12-kDa sarcoplasmic protein is found in white muscle tissue and plays a role in muscle relaxation. Cyp c 1 is resistant to heat, enzymatic degradation, and chemical denaturation, contributing to its potent allergenic properties. Recombinant forms of Cyp c 1 (rCyp c 1) have been developed for research and diagnostic applications. The clinical manifestations of allergic reactions to Cyp c 1 include anaphylaxis, angioedema, contact urticaria, erythema, gastrointestinal symptoms, neurological symptoms, oral symptoms, respiratory reactions, and urticaria. Sensitization occurs primarily through ingestion, though exposure via inhalation or skin contact. Extensive IgE cross-reactivity is observed between Cyp c 1 and parvalbumins of other fish species such as cod, grass carp, and mackerel, attributed to their amino acid sequence homology. Additionally, Cyp c 1 shares structural homology with parvalbumins of amphibians and birds.

Epidemiology

Worldwide distribution

Common carp is among the heavily farmed and widely eaten fish species and is widely distributed across the globe, including regions in Asia, Europe, Africa, North America, and Australia.

Route Of Exposure

Sensitization to fish allergens primarily occurs through ingestion via the gastrointestinal tract. Secondary sensitization can result from inhaling fish proteins, particularly in domestic or occupational settings, as well as through skin contact during fish handling, preparation, or cooking.

Clinical Relevance

Disease severity

Fish is a common trigger for IgE-mediated food allergies. Symptoms can range from mild reactions, such as oral allergy syndrome, and skin reactions like angioedema, to gastrointestinal issues including nausea and vomiting. In severe cases, fish allergies can lead to anaphylaxis, characterized by respiratory and circulatory complications. A study examined 12 children with fish sensitization who experienced grade 2 to 4 reactions, as classified by Sampson's anaphylaxis grading system, following fish consumption. Testing with specific IgE confirmed that these children had IgE antibodies targeting codfish extract and/or the key codfish and carp allergens, Gad c 1 and Cyp c 1. The IgE levels for Cyp c 1 ranged from 2.08 kUA/L to >100 kUA/L.

The Cyp c 1 allergen has been associated with various allergic reactions, including anaphylaxis, angioedema, contact urticaria, erythema, gastrointestinal symptoms, neurological symptoms, oral symptoms, respiratory reactions, and urticaria.

Agabriel et al. (2010) documented the first case of exclusive sensitization to Cyp c1 in a child with persistent allergies to fish and chicken meat.

In a study conducted in Austria, serum samples were collected from 60 patients with at least one characteristic clinical symptom and confirmed history of type I fish allergy. All fish allergic patients exhibited IgE reactivity to rCyp c 1.01, which also triggered histamine release from basophils in a dose-dependent manner.

A multicenter cross-sectional observational survey on fish allergy was carried out at six allergy centers in Italy on 56 participants. Of these, 92.8% tested positive for at least one beta-parvalbumin, and 67.8% tested positive for Cyp c 1.

Cross-reactive molecules

In a study, 26 fish-allergic patients were included to investigate and compare the structural and immunological properties of natural and recombinant parvalbumins. Among them, 25 patients demonstrated IgE reactivity to recombinant carp parvalbumin as well as both native and recombinant cod parvalbumin. A 91% inhibition of IgE binding was observed for nGad m 1 and rGad m 1.02 (cod parvalbumin), while rCyp c 1.01 showed a 76% reduction. Additionally, rCyp c 1.01 inhibited IgE binding to rGad m 1.02 by 98%, while rGad m 1.02 reduced IgE binding to rCyp c 1.01 by 86%.

In another study, 69 patients with physician-diagnosed IgE-mediated grass carp allergy were recruited from four pediatric allergy referral centers to examine the molecular and immunological properties of grass carp parvalbumin in these patients. A strong correlation was noted between grass carp IgE levels and rCyp c 1. Specific IgE levels for rCyp c 1 ranged from 0.44 to 214 kUA/L.

Diagnostics

Disease severity

Fish allergy is typically diagnosed through detailed medical history alongside specific IgE testing and/or skin tests. If these methods are inconclusive, an open or, preferably, double-blind food challenge with the suspected fish is recommended. Fish-allergic patients exhibit diverse sensitization profiles to fish allergens. Parvalbumin serves as the main biomarker for fish allergy diagnosis.

A study examined 12 children with fish sensitization who experienced grade 2 to 4 reactions, as classified by Sampson's grading system, following fish consumption. Testing confirmed that these children had IgE antibodies targeting codfish extract and/or the key codfish and carp allergens, Gad c 1 and Cyp c 1. The IgE levels for Cyp c 1 ranged from 2.08 kUA/L to >100 kUA/L.

Cross-reactivity

Parvalbumins are IgE cross-reactive fish allergens. Purified rCyp c1 has been suggested as an effective tool for the serological diagnosis of fish allergies. In an immunoblot inhibition assay, rCyp c1 completely blocked IgE binding to natural carp parvalbumin, suggesting that the majority of IgE-binding epitopes in natural Cyp c 1 are also present in rCyp c1. Furthermore, it was observed that approximately 70% of the IgE epitopes in allergen extracts from various fish species are represented in rCyp c 1.01., suggesting that rCyp c 1 may serve as a diagnostic marker for IgE-mediated cross-sensitization across multiple fish species.

Prevention And Therapy

Avoidance of fish is strongly recommended for individuals with fish allergies.

Allergen specific immunotherapy is currently not available.

Explained Results

Allergen information

Cyp c 1 is a parvalbumin found in common carp responsible for causing allergies in fish-sensitized individuals. This 12-kDa sarcoplasmic protein, found in white muscle tissue, serves as the primary allergen in numerous fish species.

Clinical relevance

Fish are a common cause of IgE-mediated food allergies, with symptoms ranging from mild oral and skin reactions to severe anaphylaxis. Isolated sensitization to rCyp c 1 has been documented in a child with persistent fish and chicken allergies. Additionally, occupational asthma and rhinoconjunctivitis linked to rCyp c 1 have been reported in fish farm workers, primarily due to inhalation exposure to parvalbumin.

Cross-reactivity

Purified rCyp c 1 is a primary cross-reactive fish allergen and serves as a marker for diagnosing IgE-mediated fish allergies. Studies show strong IgE reactivity in fish-allergic patients, with significant inhibition of IgE binding between recombinant and native parvalbumins. The high sequence similarities between Cyp c 1 and parvalbumins from other fish species, as well as amphibians and reptiles, underline its broad cross-reactivity.

Author: Turacoz

Reviewer: Dr. Michael Spangfort

Agabriel, C., P. Robert, P. Bongrand, J. Sarles and J. Vitte (2010). "Fish allergy: in Cyp c1 we trust." Allergy 65: 1483-1484.

Calamelli, E., L. Liotti, I. Beghetti, V. Piccinno, L. Serra and P. Bottau (2019). "Component-Resolved Diagnosis in Food Allergies." Medicina (Kaunas) 55.

Dijkema, D., J. A. M. Emons, A. Van de Ven and J. N. G. Oude Elberink (2022). "Fish Allergy: Fishing for Novel Diagnostic and Therapeutic Options." Clin Rev Allergy Immunol 62: 64-71.

Douladiris, N., B. Linhart, I. Swoboda, A. Gstottner, E. Vassilopoulou, F. Stolz, R. Valenta and N. G. Papadopoulos (2015). "In vivo allergenic activity of a hypoallergenic mutant of the major fish allergen Cyp c 1 evaluated by means of skin testing." J Allergy Clin Immunol 136: 493-495.

Jonsson, K., M. Barman, H. K. Brekke, B. Hesselmar, S. Johansen, A. S. Sandberg and A. E. Wold (2017). "Late introduction of fish and eggs is associated with increased risk of allergy development - results from the FARMFLORA birth cohort." Food Nutr Res 61: 1393306.

Klueber, J., D. Schrama, P. Rodrigues, H. Dickel and A. Kuehn (2019). "Fish Allergy Management: From Component-Resolved Diagnosis to Unmet Diagnostic Needs." Curr Treat Options Allergy 6: 322-337.

Kumeta, H., H. Nakayama and K. Ogura (2017). "Solution structure of the major fish allergen parvalbumin Sco j 1 derived from the Pacific mackerel." Sci Rep 7: 17160.

Lee, E. C. K., B. Trogen, K. Brady, L. S. Ford and J. Wang (2024). "The Natural History and Risk Factors for the Development of Food Allergies in Children and Adults." Curr Allergy Asthma Rep 24: 121-131.

Leung, N. Y. H., A. S. Y. Leung, K. J. Y. Xu, C. Y. Y. Wai, C. Y. Lam, G. W. K. Wong and T. F. Leung (2020). "Molecular and immunological characterization of grass carp (Ctenopharyngodon idella) parvalbumin Cten i 1: A major fish allergen in Hong Kong." Pediatr Allergy Immunol 31: 792-804.

Ma, Y., U. Griesmeier, M. Susani, C. Radauer, P. Briza, A. Erler, M. Bublin, S. Alessandri, M. Himly, S. Vazquez-Cortes, I. R. de Arellano, E. Vassilopoulou, P. Saxoni-Papageorgiou, A. C. Knulst, M. Fernandez-Rivas, K. Hoffmann-Sommergruber and H. Breiteneder (2008). "Comparison of natural and recombinant forms of the major fish allergen parvalbumin from cod and carp." Mol Nutr Food Res 52 Suppl 2: S196-207.

Mohammadi, M., K. Mokhtarian, G. A. Kardar, S. Farrokhi, E. Sadroddiny, M. R. Khorramizadeh and R. Falak (2017). "Expression of recombinant parvalbumin from wolf-herring fish and determination of its IgE-binding capability." Food Agri Immunol 28: 573-585.

Moraes, A. H., D. Ackerbauer, M. Kostadinova, M. Bublin, G. A. de Oliveira, F. Ferreira, F. C. Almeida, H. Breiteneder and A. P. Valente (2014). "Solution and high-pressure NMR studies of the structure, dynamics, and stability of the cross-reactive allergenic cod parvalbumin Gad m 1." Proteins 82: 3032-3042.

Pali-Scholl, I., R. Herzog, J. Wallmann, K. Szalai, R. Brunner, A. Lukschal, P. Karagiannis, S. C. Diesner and E. Jensen-Jarolim (2010). "Antacids and dietary supplements with an influence on the gastric pH increase the risk for food sensitization." Clin Exp Allergy 40: 1091-1098.

Pérez Carral, C., J. Martín-Lázaro and A. Ledesma (2010). "Occupational Asthma Caused by Turbot Allergy in 3 Fish-Farm Workers." J Investig Allergol Clin Immunol 20: 349-351.

Sastre, J. (2010). "Molecular diagnosis in allergy." Clin Exp Allergy 40: 1442-1460.

Sharp, M. F. and A. L. Lopata (2014). "Fish allergy: in review." Clin Rev Allergy Immunol 46: 258-271.

Sližienė, A., M. Plečkaitytė, M. Zaveckas, K. Juškaitė, V. Rudokas, G. Žvirblis and A. Žvirblienė (2022). "Monoclonal antibodies against the newly identified allergen β-enolase from common carp (Cyprinus carpio)." Food Agri Immunol 33: 129-149.

Stephen, J. N., M. F. Sharp, T. Ruethers, A. Taki, D. E. Campbell and A. L. Lopata (2017). "Allergenicity of bony and cartilaginous fish - molecular and immunological properties." Clin Exp Allergy 47: 300-312.

Swoboda, I., A. Bugajska-Schretter, P. Verdino, W. Keller, W. R. Sperr, P. Valent, R. Valenta and S. Spitzauer (2002). "Recombinant carp parvalbumin, the major cross-reactive fish allergen: a tool for diagnosis and therapy of fish allergy." J Immunol 168: 4576-4584.

Villalta, D., E. Scala, G. Deleonardi, M. Busa, F. Rivolta, E. Boni, G. Gabrielli, L. Farioli, C. Cappelletti, F. Buzzulini, M. Conte, V. Pravettoni and R. Asero (2022). "A comprehensive molecular approach in fish allergy: Usefulness in daily clinical practice." Clin Chim Acta 533: 104-108.

Wai, C. Y. Y., N. Y. H. Leung, A. S. Y. Leung, N. Fusayasu, S. Sato, K. J. Y. Xu, Y. S. Yau, J. S. Rosa Duque, M. Y. W. Kwan, J. Cheng, W. H. Chan, G. T. Chua, Q. U. Lee, D. C. K. Luk, P. K. Ho, J. S. C. Wong, I. C. S. Lam, G. W. K. Wong, M. Ebisawa and T. F. Leung (2023). "Differential patterns of fish sensitization in Asian populations: Implication for precision diagnosis." Allergol Int 72: 458-465.

WHO/IUIS. (2019). "Cyp c 1." Retrieved December 3, 2024, from https://www.allergen.org/viewallergen.php?aid=781.

Zuidmeer-Jongejan, L., H. Huber, I. Swoboda, N. Rigby, S. A. Versteeg, B. M. Jensen, S. Quaak, J. H. Akkerdaas, L. Blom, J. Asturias, C. Bindslev-Jensen, M. L. Bernardi, M. Clausen, R. Ferrara, M. Hauer, J. Heyse, S. Kopp, M. L. Kowalski, A. Lewandowska-Polak, B. Linhart, B. Maderegger, B. Maillere, A. Mari, A. Martinez, E. N. Mills, A. Neubauer, C. Nicoletti, N. G. Papadopoulos, A. Portoles, V. Ranta-Panula, S. Santos-Magadan, H. J. Schnoor, S. T. Sigurdardottir, P. Stahl-Skov, G. Stavroulakis, G. Stegfellner, S. Vazquez-Cortes, M. Witten, F. Stolz, L. K. Poulsen, M. Fernandez-Rivas, R. Valenta and R. van Ree (2015). "Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy." Int Arch Allergy Immunol 166: 41-51.