Actin Allergen of Common Periwinkle Sea Snail (Littorina Littorea

Practitioner's Corner 150

References Actin Allergen of Common Periwinkle Sea Snail 1. Shah R, Grammer LC. Chapter 1: an overview of allergens. (Littorina littorea) Allergy Asthma Proc. 2012;33 Suppl 1:S2-5. 2. Wilson AF, Novey HS, Berke RA, Surprenant EL. Deposition of González-Mancebo E1,5, Trujillo-Trujillo MJ1,5, Gandolfo- inhaled pollen and pollen extract in human airways. N Engl J Cano M1,5, Mohedano-Vicente E1,5, Cuesta-Herranz J2,5, Med. 1973;288:1056-8. Bartolome B3*, Pastor-Vargas C4,5* 3. Cheng Y, Smith SM, Yeh H. Deposition of ultrafine particles 1Allergy Unit, Hospital Universitario de Fuenlabrada, IdiPAZ, in human tracheobronchial airways. Ann Occup Hyg. Madrid, Spain 1997;41:714-8. 2Allergy Department, IIS-Fundación Jiménez Díaz, UAM, Madrid, 4. Taylor PE, Flagan RC, Valenta R, Glovsky MM. Release of Spain allergens as respirable aerosols: A link between grass pollen 3R+D Department, Roxall, Bilbao, Spain and asthma. J Allergy Clin Immunol. 2002;109:51-6. 4Department of Immunology, IIS-Fundación Jiménez Díaz, UAM, 5. Rick EM, Woolnough K, Pashley CH, Wardlaw AJ. Allergic Madrid, Spain Fungal Airway Disease. J Investig Allergol Clin Immunol. 5ARADyAL Network, Instituto de Salud Carlos III, Madrid, Spain 2016;26(6):344-54. *Both authors should be considered last authors 6. Ferguson P, Broide DH. Environmental and bronchoalveolar lavage Dermatophagoides pteronyssinus antigen levels in J Investig Allergol Clin Immunol 2019; Vol. 29(2): 150-152 atopic asthmatics. Am J Respir Crit Care Med. 1995;151:71-4. doi: 10.18176/jiaci.0356 7. Horvath A, Balashazy I, Farkas A, Sarkany Z, Hofmann W, Czitrovszky A, et al. Quantification of airway deposition Key words: Shellfish allergy. Mollusk allergy. Periwinkle allergy. Actin. of intact and fragmented pollens. Int J Environ Heat R. Tropomyosin. 2011;21:427-40. Palabras clave: Alergia a marisco. Alergia a moluscos. Alergia a bígaro. 8. Demoly P, Matucci A, Rossi O, Vidal C. A year-long, fortnightly, Actina. Tropomiosina. observational survey in three European countries of patients with respiratory allergies induced by house dust mites: Methodology, demographics and clinical characteristics. BMC Pulm Med. 2016;16:85. 9. Gomez de Ana S, Torres-Rodríguez JM, Ramírez EA, García Shellfish are one of the main food allergens in adults SM, Belmonte-Soler J.J. Seasonal distribution of Alternaria, and include a diverse group of species with shells or shell- Aspergillus, Cladosporium and Penicillium species isolated like exo- or endoskeletons. They comprise both crustaceans in homes of fungal allergic patients. J Investig Allergol Clin and mollusks. Mollusks include gastropods (limpets, snails, Immunol. 2006;16:357-63. winkles, and abalone), bivalves (mussels, clams, razor fish, oysters, and scallops), and cephalopods (squid, cuttlefish, and octopus). Shellfish are an important food source and are consumed throughout the world [1]. Japan and other coastal regions of Asia are major mollusk consumers [1]. Countries in southern Europe (Spain, France, Italy, and Portugal) also Manuscript received October 17, 2018; accepted for publication consume high quantities of mollusks and crustaceans [1]. November 14, 2018. Mollusk allergies have been documented with gastropods, bivalves, and cephalopods [1]. Although the importance of Jerónimo Carnés mollusk allergy is becoming increasingly recognized, its Research & Development Laboratorios LETI, S.L.U. prevalence is unknown. Mollusks were responsible for 5.6% E-mail: [email protected] to 11.7% of severe allergic reactions in France during 2002 and 2003 and are reported to have caused 36% of cases of anaphylaxis in Singapore during the same period [1]. The common periwinkle (Littorina littorea) is a marine gastropod mollusk that has gills, an operculum, and a dark and sometimes banded shell. It is a member of the Littorinidae family. Common periwinkles are native to the northeastern coasts of the Atlantic Ocean (northern Spain, France, England, Wales, Scotland, Ireland, Scandinavia, and Russia). They are eaten in coastal areas of Spain, Scotland, England, Wales, and Ireland. Periwinkles are highly valued in African and Asian cuisine. The meat is high in protein and ω-3 fatty acids and low in fat (http: wikipedia.org/wiki/Common_periwinkle). We report the case of a 49-year-old woman who developed symptoms after consuming periwinkles. Two hours after eating cooked periwinkles (approximately 250 mg) and

rice with vegetables at home, she presented with bilateral Raw and cooked protein extracts of L littorea were palpebral angioedema and generalized urticaria, but no other prepared by homogenization in phosphate-buffered saline symptoms. She denied having exercised or ingested alcohol (20% wt/vol), dialyzation, and lyophilization. The extracts or nonsteroidal anti-inflammatory drugs. She was attended in were analyzed using SDS-PAGE under reducing conditions the emergency department, and her symptoms resolved within (as described by Laemmli), which showed protein bands 3 hours of treatment with intramuscular dexchlorpheniramine ranging from 90 kDa to 14 kDa in both extracts (results not and methylprednisolone. Since then, the patient has tolerated shown). SDS-PAGE IgE-immunoblotting assays with both all the foods eaten at the time, as well as other shellfish raw and cooked periwinkle extracts revealed an intense IgE- (prawns, razor clams, mussels, and squid), although she has reactive band of 31 kDa and a very faint one of 28 kDa. An not eaten periwinkle again. She had no previous history of IgG-immunoblotting assay with this extract and rabbit serum rhinitis or asthma, atopic dermatitis, or food allergy. against Penaeus species tropomyosin revealed an IgG binding Three months later, and after obtaining the patient's band of 39 kDa (Figure), this result led us to deduce that the informed consent, skin prick tests were performed with 31-kDa IgE-reactive band was not tropomyosin. commercial extracts from fish (hake, cod, trout, tuna, salmon, The intense 31-kDa IgE-binding protein was manually sardine, and monkfish), shellfish (prawn, lobster, crab, clam, excised, digested with trypsin, and analyzed by mass mussel, snail, and squid), and Anisakis simplex (Roxall Group, spectrometry in tandem, as previously described [2]. Proteins Bilbao, Spain). All results were negative. The results of skin were identified by searching a nonredundant protein sequence prick tests with commercial extracts and prick-by-prick tests database (NCBI). The analysis of the resulting peptides by with the remaining foods the patient ate were also negative, as mass spectrometry revealed the protein to be actin. were skin prick tests with commercial pollen, mites, dander, Tropomyosin is the allergen most frequently involved and mold extracts. Prick-by-prick tests with raw and cooked in mollusk allergy [3] and is also responsible for most cases periwinkle were both positive (wheal, 5 mm and 5 mm, of cross-reactivity between mollusks and crustaceans [3]. respectively). Prick-by-prick tests with raw and cooked mussel, However, tropomyosin does not appear to be implicated squid, and prawn were negative. Positive and negative results in some patients who are allergic to mollusks but tolerate were obtained for controls (histamine and saline respectively). crustaceans [4]. Cross-reactivity between mollusks is usually The patient’s total serum IgE was 4 IU/mL, and the results found within species of the same class (bivalves, cephalopods, of specific IgE determination with clam, crab, prawn, squid, and gastropods) [1]. In addition to tropomyosin, several lobster, and snail were negative (<0.1 kUA/L) (ImmunoCAP, allergens have been described in mollusks, namely, actin [4], Thermo Fisher Scientific). The patient refused to undergo oral paramyosin [5], myosin heavy chain [6], amylase [7], challenge with periwinkle. hemocyanin [8] (amylase and hemocyanin may be involved in cross-reactivity between mollusk and house-dust mite aeroallergens), enolase [4], C1q domain-containing protein [4], A B arginine kinase [9], and triose phosphate isomerase [10]. At P C P C S C1 M kDa least 3 of these are also allergens in crustaceans, namely, tropomyosin, arginine kinase, and triose phosphate isomerase 97.0 (www.allergen.org). We present the case of a patient who was monoallergic 66.0 to periwinkle and who tolerated all other mollusks and crustaceans tested (negative results in skin prick and specific 45.0 IgE testing). The heat-stable 31-kDa protein identified as actin was likely responsible for the patient’s allergic symptoms. Our review of the literature indicates that this is the first reported case of allergy to common periwinkle sea snail (L littorea).

30.0 Funding This study was supported by grants from Instituto de Salud Carlos III and the Thematic Network and Co- operative Research Centers ARADyAL RD16/0006/0013 and 20.1 RD16/0006/0022. The study was cofunded by FEDER grants.

Conflicts of Interest

14.4 The authors declare that they have no conflicts of interest.

Figure. SDS-PAGE immunoblotting. A, Raw periwinkle extract. B, Cooked References periwinkle extract. Lane P, patient’s serum; Lane C, control serum (pool of sera from nonatopic individuals); Lane S, rabbit serum against Penaeus 1. Khora SS. Seafood-Associated Shellfish Allergy: A species tropomyosin; Lane C 1, serum from nonimmunized rabbit; Lane M, molecular mass standard. Comprehensive Review. Immunol Invest. 2016;4:504-30.

2. Pastor C, Cuesta-Herranz J, Cases B, Perez-Gordo M, Figueredo E, de las Heras M, et al. Identification of major allergens in Actin as a Possible Cross-Reactive Allergen Between watermelon. Int Arch Allergy Immunol. 2009;149:291-8. Fish and Poultry 3. Vidal C, Bartolomé B, Rodríguez V, Armisén M, Linneberg A, González-Quintela A. Sensitization pattern of crustacean- Barbarroja-Escudero J1, Sánchez-González MJ1, Bartolomé B2, allergic individuals can indicate allergy to molluscs. Allergy. Pastor-Vargas C3,4, Rodríguez-Rodríguez M1, Cuesta-Herranz J4,5, 2015;70:1493-6. Alvarez-Mon M1 4. Azofra J, Echechipía S, Irazábal B, Muñoz D, Bernedo N, García 1Servicio de Enfermedades del Sistema Inmune-Alergia, Hospital BE, et al. Heterogeneity in allergy to mollusks: a clinical- Universitario Príncipe de Asturias, Departamento de Medicina immunological study in a population from the North of Spain. y Especialidades Médicas, Universidad de Alcalá, Alcalá de J Investig Allergol Clin Immunol. 2017;27:252-60. Henares, Spain 5. Suzuki M, Kobayashi Y, Hiraki Y, Nakata H, Shiomi K. Paramyosin 2Application Laboratory, R&D Department, Roxall Group, of the Disc abalone Haliotis discus discus: identification as Bilbao, Spain a new allergen and cross-reactivity with tropomyosin. Food 3Department of Immunology, Hospital Universitario Fundacion Chem. 2011;124:921-6. Jimenez Diaz, Instituto de Investigación Sanitaria (IIS-FJD, 6. Martins LM, Peltre G, da Costa Faro CJ, Pires EM, da Cruz UAM), Madrid, Spain Inácio FF. The Helix aspersa (brown garden snail) allergen 4RETIC ARADyAL, Instituto de Salud Carlos III, Spain repertoire. Int Arch Allergy Immunol. 2005;136:7-15. 5Department of Allergy, Hospital Universitario Fundación 7. Popescu FD. Cross-reactivity between aeroallergens and food Jimenez Diaz, Instituto de Investigación Sanitaria Fundacion allergens. World J Methodol. 2015;5:31-50. Jimenez Diaz (IIS-FJD, UAM), Madrid, Spain 8. Oyelaran O, Gildersleeve JC. Evaluation of human antibody responses to keyhole limpet hemocyanin on a carbohydrate J Investig Allergol Clin Immunol 2019; Vol. 29(2): 152-154 microarray. Proteomics Clin Appl. 2010;4:285-94. doi: 10.18176/jiaci.0357 9. Shen HW, Cao MJ, Cai QF, Ruan MM, Mao HY, Su WJ, et al. Purification, cloning, and immunological characterization of Key words: Actin. Aldolase. Enolase. Fish-chicken syndrome. arginine kinase, a novel allergen of Octopus fangsiao. J Agric Parvalbumin. Food Chem. 2012;60:2190-9. 10. Yang Y, Chen ZW, Hurlburt BK, Li GL, Zhang YX, Fei DX, et Palabras clave: Actina. Aldolasa. Enolasa. Síndrome pescado-ave. Parvalbúmina. al. Identification of triosephosphate isomerase as a novel allergen in Octopus fangsiao. Mol Immunol. 2017;85:35-46

Fish and chicken are widely consumed [1,2]. Both fish allergy and chicken allergy without associated hypersensitivity to egg and/or bird feather have been reported [1,3]. A Manuscript received July 2, 2018; accepted for publication November 19, 2018. new syndrome, fish-chicken syndrome, which involves 3 possible cross-reactive allergens has been proposed [1]. To Eloína González-Mancebo our knowledge, the present case is the first report of cross- Unidad de Alergia reactivity between fish and chicken due to a protein not yet Hospital Universitario de Fuenlabrada associated with these foods. Fuenlabrada (Madrid), Spain A 43-year-old man diagnosed with mild seasonal pollen- E-mail: [email protected] triggered rhinoconjunctivitis experienced several episodes of urticaria, abdominal pain, and dyspnea within a few minutes of eating various types of fish between 1997 and 2002. In 2015, he experienced several episodes of oropharyngeal pruritus, generalized urticaria, and facial angioedema after eating chicken and turkey. He subsequently experienced generalized urticaria, facial angioedema, dysphonia, abdominal pain, vomiting, and dyspnea several minutes after inadvertently eating both types of poultry in meat puddings. Nowadays, he avoids all types of fish and poultry, but tolerates shellfish, mammalian meats, and other foods. Skin prick tests (SPTs) were performed with a battery of extracts from aeroallergens (pollen, house dust mite, dander, and fungi), meats (chicken, lamb, pig, and cow), fish (hake, cod, sole, anchovy, sardine, salmon, and tuna), Anisakis simplex, and shellfish (clam, mussel, squid, and prawn). SPTs were also performed with negative controls (50% glycerinated saline) and positive controls (histamine, 10 mg/mL) (ALK-