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Ask The Expert

July 30, 2013

Relationship of Dust Mites and Crustaceans

Question

“While it has been reported that up to 15% of patients highly sensitized to dust mites are also sensitized to crustaceans, e.g. shrimp and snails, due largely to the cross-reacting anti-tropomyosin IgE, is there risk of inducing clinically significant allergic reactions to the crustaceans while treating patients with dust mite immunotherapy? Should patients highly allergic to dust mites be advised to avoid eating crustaceans?”

Answer

By Dr. Enrique Fernandez-Caldas

Tropomyosins represent Group 10 mite allergens. This group has now been described in 10 different mite species[1]. They are involved in muscle contraction in invertebrates and are present in low concentrations in mite bodies and extracts. The invertebrate tropomyosins are allergenic in man with high IgE cross-reactivity and, therefore, are referred to as pan-allergens. Der f 10 and Der p 10 are allergens with significant homology with tropomyosins from different species[2]  and are involved in the cross-reactivity process between mites, mollusks, crustaceans, and insects in shrimp-allergic patients[3].  Allergenic cross-reactivity exists between Der p 10 and Blo t 10 from Blomia tropicalis. Although Blo t 10 and Der p 10 are highly conserved and significantly cross-react, unique IgE epitopes do exist[4]. Der p 10 is recognized by 10 to 20% of HDM-allergic patients, depending on the geographical. Der p 10-negative patients are primarily sensitized to Der p 1 and/or Der p 2, whereas Der p 10-positive patients react to several other HDM allergens, besides the major allergens (Der p 1 and Der p 2), or demonstrate an uncommon rather selective Der p 10 reactivity. The allergenic activity of Der p 10 is generally low, but some patients can be identified as suffering from clinically relevant HDM allergy due to Der p 10 sensitization[5]. There is no contraindication for mite immunotherapy in patients showing specific IgE responses to Der p 1, Der p 2 and mite group 10 allergens. However, since these patients tend to be polysensitized, mite immunotherapy should be applied more cautiously.

Individuals allergic to the Dermatophagoides ssp. may experience allergic symptoms after the consumption of crustaceans and mollusks. The 36 kDa cross-reactive tropomyosin present in mites, various insects (chironomids, mosquito, and cockroach), and shrimp[6] is responsible for cross-reactivity among different arthropods[7]. Immunochemical studies demonstrate that allergens from snails, crustaceans, cockroaches, and chironomids cross-react with house dust mite allergens. However, house dust mites are usually the primary source of sensitizing allergens. The nematode, Anisakis simplex, a common fish parasite, can be a hidden food allergen, inducing IgE-mediated reactions. Allergic cross-reactivity between this nematode and the domestic mites A. siro, L. destructor, T. putrescentiae, and D. pteronyssinus is reported, in which tropomyosin seems to be involved[8]. Tropomyosin is also involved in the cross-reactivity between mites and human parasites. A high degree of IgE cross-reactivity between allergenic extracts from house dust mites and Ascaris has been demonstrated with the participation of several allergens including tropomyosin and glutathione-s-tranferases[9]. The allergenic cross-reactivity between Blo t 10 and Ascaris tropomyosin was demonstrated using sera from asthmatic mite-allergic patients. A. lumbricoides tropomyosin (Asc l 3) is an allergen cross-reactive with mite tropomyosins. IgE reactivity to this allergen is very frequent in both asthmatic and normal subjects sensitized to Ascaris extract[10]. Evidence suggests that cross-reactivity between mites and Ascaris tropomyosins could be important. In many cases, sensitization to mite tropomyosin could also be a marker of previous exposure to parasites, and other other allergens. Moreover, IgE antibody reactivity to shrimp tropomyosin can occur in unexposed populations of individuals since subjects allergic to mites and/or cockroach may show substantial IgE antibody reactivity to the major shrimp allergen Pen a 1[11]. Based on inhibition with cockroach and/or dust mite extracts, this reactivity appears to be due to cross-reacting tropomyosins. Furthermore, filarial and mite tropomyosins are very similar, with 72% identity at the aminoacid level and overlapping predicted 3D structures. Filarial infection induces strong cross-reactive antitropomyosin antibody responses that may affect sensitization and regulation of the allergic reactivity, especially in the tropics. The prevalence of IgE and IgG to Der p 10 was increased in Filaria-infected individuals compared with uninfected subjects. Antifilarial tropomyosin IgE is entirely cross-reactive with Der p 10 using sera from experimentally filaria-infected non-human primates [12].

Patients sensitized to house dust mites can be subdivided on the basis of their component-resolved responses into two main groups: those sensitized only to the house dust mite major allergens (group 1 and group 2 in the Pyroglyphid mites) and those with a broader pattern of sensitization, including highly cross-reactive epitopes (e.g., the group 10 tropomyosins). In geographic areas with dual or multiple mite species exposure, component-resolved diagnosis of allergic diseases in children enables better definition of clinical reactivity, challenge-associated severity and prognostic accuracy than the commonly available quantitative, allergen-specific tests. As such, it is likely that these tests will become available for both diagnostic and therapeutic use. These data are important for the future formulation of a component-based immunomodulatory vaccine as well as to tailor immunotherapy for individual patients.

From the clinical point of view, the potential cross reactivity between mites and shrimps prompts several questions. 1) Are patients with respiratory symptoms linked to mite sensitization and exposure more prone to experience adverse reactions when eating shellfish? 2) Are patients with only digestive or cutaneous symptoms due to shrimp ingestion, more in danger to develop asthma and/or rhinitis due to mite sensitization? 3) Can mite sensitized patients with only respiratory symptoms became sensitized to new allergens and become food allergic to crustaceans as a result of mite immunotherapy? And 4) Could mite immunotherapy be useful to attenuate digestive and/or cutaneous symptoms in patients clinically sensitized to mites, snails and crustaceans?

The published evidence points out in the direction that sensitization to tropomyosin in house dust mite allergic patients is scarcer than expected. In a large multicentre study in Spain a total of 477 sera of house dust mite allergic patients (positive skin prick test,) were screened for IgE antibodies to tropomyosin (Der p 10) the prevalence of IgE-sensitization to tropomyosin (Der p 10/Pen a 1) was low (5-10%) and was not associated with either a particular mite species or mite allergen exposure levels. Moreover, very few patients were found to be exclusively sensitized to tropomyosin. Sensitization to tropomyosin may indicate a true food allergy independent of mite respiratory disease[13]. These low prevalence figures are also detected in other studies[14],[15] which suggest different patterns in food and mite-related tropomyosin sensitization. The second question seems to be even more improbable, since in a recent review[16], the prevalence of respiratory symptoms in patients with food allergy does not seem to be significantly different, excluding symptoms related to anaphylactic reactions. Regarding shrimp sensitized patients receiving mite immunotherapy, several contradicting reports have been published. In one of these articles the authors concluded that the improvement in respiratory symptoms and in food challenges for shrimps during mite immunotherapy with a high dosage of tropomyosin in the extracts corroborates the hypothesis that efficacy of mite immunotherapy in food allergy to tropomyosin may be dose dependent[17]. Other studies have shown a lack of de novo sensitization to tropomyosin in a group of mite-allergic patients treated by house dust mite-specific immunotherapy [18]. Sensitization and clinical symptoms to seafood (lobster) may also happen in the absence of sensitization to tropomyosin[19]. However other studies have produced the opposite results[20]. It is noteworthy that the most recent studies have shown a lack of food allergy induction and sensitization to new food allergens, which may imply a difference between previously used and current mite allergen extracts.

Based on current evidence, house dust mite allergic patients should not be advised to not eat shrimps, or to stop eating shrimps, based only on positive skin tests, or an in vitro positive specific IgE determination to mite tropomyosin. It should neither be a deterrent for starting mite immunotherapy in well selected mite allergic patients who are sensitized to tropomyosin. A positive specific IgE to tropomyosin could be due to many different factors, including cross-reactivity and co-sensitization. Shrimp allergy in mite allergic individuals could be due to parallel phenomena and not a consequence of each other.

References

[1].         Fernández-Caldas E, Puerta L, Caraballo L, Lockey RF.Mite allergens. Clin Allergy Immunol. 2008;21:161-82.

[2].         Aki T, Kodama T, Fujikawa A, Miura K, Shigeta S, et al. Immunochemical characterization of recombinant and native tropomyosin as a new allergen from the house dust mite , Dermatophagoides farinae. J Allergy Clin Immunol 1995; 96:74-83.

[3].         Witteman A, Akkerdaas J, Leeuwen J, van der Zee J, Aalberse RC. Identification of a cross-reactive allergen (presumably tropomyosin) in Shrimp, mite and insects, In Arch Allergy Immunol 1994; 105:56-61.

[4].         Yi FC, Cheong N, Shek PC, Wang DY, Chua KY, Lee BW. Identification of shared and unique immunoglobulin E epitopes of the highly conserved tropomyosins in Blomia tropicalis and Dermatophagoides pteronyssinus. Clin Exp Allergy 2002;32:1203-10.

[5].         Resch Y, Weghofer M, Seiberler S, Horak F, Scheiblhofer S, Linhart B, Swoboda I, Thomas WR, Thalhamer J, Valenta R, Vrtala S. Molecular characterization of Der p 10: a diagnostic marker for broad sensitization in house dust mite allergy. Clin Exp Allergy. 2011 Oct;41(10):1468-77.

[6].         Witteman AM, Akkerdaas JH, van Leeuwen J, van der Zee JS, Aalberse RC. Identification of a cross-reactive allergen (presumably tropomyosin) in shrimp, mite and insects. Int Arch Allergy Immunol. 1994 Sep;105(1):56-61.  Identification of a cross-reactive allergen (presumably tropomyosin) in shrimp, mite and insects. Int Arch Allergy Immunol 1994, 105:56–61.

[7].         van Ree R, Antonicelli L, Akkerdaas JH, Pajno GB, Barberio G, Corbetta L, Ferro G, Zambito M, Garritani MS, Aalberse RC, Bonifazi F. Asthma after consumption of snails in house-dust-mite-allergic patients: a case of IgE cross-reactivity. Allergy. 1996;51(6):387-93.

[8].         Johansson E, Aponno M, Lundberg M, van Hage-Hamsten M. Allergenic cross-reactivity between the nematode Anisakis simplex and the dust mites Acarus siro, Lepidoglyphus destructor, Tyrophagus putrescentiae, and Dermatophagoides pteronyssinus. Allergy 2001, 56:660–666.

[9].         Acevedo N, Sánchez J, Erler A, Mercado D, Briza P, Kennedy M, Fernandez A, Gutierrez M, Chua KY, Cheong N, Jiménez S, Puerta L, Caraballo L. IgE cross-reactivity between Ascaris and domestic mite allergens: the role of tropomyosin and the nematode polyprotein ABA-1. Allergy. 2009 Nov;64(11):1635-43.

[10].       Acevedo N, Erler A, Briza P, Puccio F, Ferreira F, Caraballo L. Allergenicity of Ascaris lumbricoides tropomyosin and IgE sensitization among asthmatic patients in a tropical environment. Int Arch Allergy Immunol. 2011;154(3):195-206.

[11].       Fernandes J, Reshef A, Patton L, Ayuso R, Reese G, Lehrer SB. Immunoglobulin E antibody reactivity to the major shrimp allergen, tropomyosin, in unexposed Orthodox Jews. Clin Exp Allergy. 2003 Jul;33(7):956-61.

[12].       Santiago HC, Bennuru S, Boyd A, Eberhard M, Nutman TB. Structural and immunologic cross reactivity among filarial and mite tropomyosin: implications for the hygiene hypothesis. J Allergy Clin Immunol. 2010;127:479-86.

[13].       Barber D, Arias J, Boquete M, Cardona V, Carrillo T, Gala G, Gamboa P, García-Robaina JC, Hernández D, Sanz ML, Tabar AI, Vidal C, Ipsen H, de la Torre  F, Lombardero M. Analysis of mite allergic patients in a diverse territory by improved diagnostic tools. Clin Exp Allergy. 2012;42(7):1129-38.

[14].       Becker S, Gröger M, Canis M, Pfrogner E, Kramer MF. Tropomyosin sensitization  in house dust mite allergic patients. Eur Arch Otorhinolaryngol. 2012;269(4):1291-6

[15].       Bronnert M, Mancini J, Birnbaum J, Agabriel C, Liabeuf V, Porri F, Cleach I,Fabre A, Deneux I, Grandné V, Grob JJ, Berbis P, Charpin D, Bongrand P, Vitte J. Component-resolved diagnosis with commercially available D. pteronyssinus Der p 1, Der p 2 and Der p 10: relevant markers for house dust mite allergy. Clin Exp Allergy. 2012 Sep;42(9):1406-15).

[16].       Lopata AL, O'Hehir RE, Lehrer SB. Shellfish allergy. Clin Exp Allergy. 2010;40(6):850-8.

[17].       Cortellini G, Spadolini I, Santucci A, Cova V, Conti C, Corvetta A, Passalacqua G. Improvement of shrimp allergy after sublingual immunotherapy for house dust mites: a case report. Eur Ann Allergy Clin Immunol. 2011 Oct;43(5):162-4.

[18].       Asero R. Lack of de novo sensitization to tropomyosin in a group of mite-allergic patients treated by house dust mite-specific immunotherapy. Int Arch Allergy Immunol. 2005 May;137(1):62-5.

[19].       Iparraguirre A, Rodríguez-Pérez R, Juste S, Ledesma A, Moneo I, Caballero ML. Selective allergy to lobster in a case of primary sensitization to house dust mites. J Investig Allergol Clin Immunol. 2009;19(5):409-13.

[20].       van Ree R, Antonicelli L, Akkerdaas JH, Garritani MS, Aalberse RC, Bonifazi F. Possible induction of food allergy during mite immunotherapy. Allergy. 1996 Feb;51(2):108-13.


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