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How molecular diagnostics help us to correctly identify pet allergies

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Summary

Simultaneous sensitization to two or more animal species is common and represents a regular diagnostic problem during conventional extract-based allergy diagnosis. The use of single allergen molecules reveals the underlying cause of polysensitization and enables the distinction between primary sensitization and cross-reaction as a prerequisite for the selection of appropriate immunotherapy vaccines. Individual sensitization patterns can be valuable predictors of clinical relevance, symptom severity and asthma risk, and in part reflect current or past animal exposure. The concept of “marker allergens” is challenging in the case of pet allergies because many animal allergens are ubiquitous pan-allergens limiting the definition of group-specific markers. Alternatively, quantitative aspects often have to be used to identify the primary sensitizers. A sufficient number of allergen molecules is now available from cat and dog to unravel the many cases of cat–dog double sensitization. There are still substantial diagnostic gaps concerning allergens from small animals and farm animals, or such allergens are only available for multiplex testing. The lipocalins, a particularly species-rich and heterogeneous allergen family comprising important major and minor allergens from virtually all furry animals, show complex cross-reactivity patterns with each other and have been recently identified as a major cause of polysensitization.

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References

  1. Bousquet PJ, Chinn S, Janson C, Kogevinas M, Burney P, Jarvis D. Geographical variation in the prevalence of positive skin tests to environmental aeroallergens in the European community respiratory health survey I. Allergy. 2007;62:301–9.

    Article  PubMed  Google Scholar 

  2. Kolli F, Breyer MK, Hartl S, Burghuber O, Wouters EFM, Sigsgaard T, et al. Aero-allergen sensitization in the general population: longitudinal analyses of the LEAD (lung heart social body) study. J Asthma Allergy. 2022;15:461–73.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sander I, Lotz A, Neumann HD, Czibor C, Flagge A, Zahradnik E, et al. Indoor allergen levels in settled airborne dust are higher in day-care centers than at home. Allergy. 2018;73:1263–75.

    Article  CAS  PubMed  Google Scholar 

  4. Zahradnik E, Raulf M. Animal allergens and their presence in the environment. Front Immunol. 2014;5:76.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bjerg A, Winberg A, Berthold M, Mattsson L, Borres MP, Rönmark E. A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren. Pediatr Allergy Immunol. 2015;26:557–63.

    Article  PubMed  Google Scholar 

  6. van Hage M, Käck U, Asarnoj A, Konradsen JR. An update on the prevalence and diagnosis of cat and dog allergy—emphasizing the role of molecular allergy diagnostics. Mol Immunol. 2023;157:1–7.

    Article  PubMed  Google Scholar 

  7. Hemmer W, Sestak-Greinecker G, Braunsteiner T, Wantke F, Wöhrl S. Molecular sensitization patterns in animal allergy: relationship with clinical relevance and pet ownership. Allergy. 2021;76:3687–96.

    Article  CAS  PubMed  Google Scholar 

  8. Kleine-Tebbe J, Matricardi PM, Hamilton RG. Allergy work-up including component-resolved diagnosis: how to make allergen-specific immunotherapy more specific. Immunol Allergy Clin North Am. 2016;36:191–203.

    Article  PubMed  Google Scholar 

  9. Seismann H, Blank S, Braren I, Greunke K, Cifuentes L, Grunwald T, et al. Dissecting cross-reactivity in hymenoptera venom allergy by circumvention of alpha‑1,3‑core fucosylation. Mol Immunol. 2010;47:799–808.

    Article  CAS  PubMed  Google Scholar 

  10. Grönlund H, Adédoyin J, Reininger R, Varga EM, Zach M, Fredriksson M, et al. Higher immunoglobulin E antibody levels to recombinant Fel d 1 in cat-allergic children with asthma compared with rhinoconjunctivitis. Clin Exp Allergy. 2008;38:1275–81.

    Article  PubMed  Google Scholar 

  11. Asarnoj A, Hamsten C, Wadén K, Lupinek C, Andersson N, Kull I, Curin M, et al. Sensitization to cat and dog allergen molecules in childhood and prediction of symptoms of cat and dog allergy in adolescence: a BAMSE/MeDALL study. J Allergy Clin Immunol. 2016;137:813–21.

    Article  CAS  PubMed  Google Scholar 

  12. Hilger C, Kler S, Arumugam K, Revets D, Muller CP, Charpentier C, et al. Identification and isolation of a Fel d 1‑like molecule as a major rabbit allergen. J Allergy Clin Immunol. 2014;133:759–66.

    Article  CAS  PubMed  Google Scholar 

  13. Reininger R, Varga EM, Zach M, Balic N, Lindemeier AD, Swoboda I, et al. Detection of an allergen in dog dander that cross-reacts with the major cat allergen, Fel d 1. Clin Exp Allergy. 2007;37:116–24.

    Article  CAS  PubMed  Google Scholar 

  14. McDonald RE, Fleming RI, Beeley JG, Bovell DL, Lu JR, Zhao X, et al. Latherin: a surfactant protein of horse sweat and saliva. PLoS One. 2009;4:e5726.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Smith W, O’Neil SE, Hales BJ, Chai TL, Hazell LA, Tanyaratsrisakul S, et al. Two newly identified cat allergens: the von Ebner gland protein Fel d 7 and the latherin-like protein Fel d 8. Int Arch Allergy Immunol. 2011;156:159–70.

    Article  CAS  PubMed  Google Scholar 

  16. Suzuki S, Nwaru BI, Ekerljung L, Sjölander S, Mincheva R, Rönmark EP, et al. Characterization of sensitization to furry animal allergen components in an adult population. Clin Exp Allergy. 2019;49:495–505.

    Article  CAS  PubMed  Google Scholar 

  17. Vachová M, Panzner P, Vlas T, Vítovcová P. Analysis of sensitization profiles in Central European allergy patients focused on animal allergen molecules. Int Arch Allergy Immunol. 2020;4:1–7.

    Google Scholar 

  18. Villalta D, Milanese M, Da Re M, Sabatino G, Sforza M, Calzetta L, et al. Frequency of allergic sensitization to Can f 5 in north east Italy. An analysis of 1403 ISAcs 112 (component resolved diagnosis) collected retrospectively. Eur Ann Allergy Clin Immunol. 2019;51:186–9.

    Article  CAS  PubMed  Google Scholar 

  19. Mattsson L, Lundgren T, Everberg H, Larsson H, Lidholm J. Prostatic kallikrein: a new major dog allergen. J Allergy Clin Immunol. 2009;123:362–8.

    Article  CAS  PubMed  Google Scholar 

  20. Weidinger S, Mayerhofer A, Raemsch R, Ring J, Köhn FM. Prostate-specific antigen as allergen in human seminal plasma allergy. J Allergy Clin Immunol. 2006;117:213–5.

    Article  CAS  PubMed  Google Scholar 

  21. Kofler L, Kofler H, Mattsson L, Lidholm J. A case of dog-related human seminal plasma allergy. Eur Ann Allergy Clin Immunol. 2012;44:89–92.

    CAS  PubMed  Google Scholar 

  22. Basagaña M, Bartolomé B, Pastor C, Torres F, Alonso R, Vivanco F, et al. Allergy to human seminal fluid: cross-reactivity with dog dander. J Allergy Clin Immunol. 2008;121:233–9.

    Article  PubMed  Google Scholar 

  23. Curin M, Swoboda I, Wollmann E, Lupinek C, Spitzauer S, van Hage M, et al. Microarrayed dog, cat, and horse allergens show weak correlation between allergen-specific IgE and IgG responses. J Allergy Clin Immunol. 2014;133:918–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hilger C, Kohnen M, Grigioni F, Lehners C, Hentges F. Allergic cross-reactions between cat and pig serum albumin. Study at the protein and DNA levels. Allergy. 1997;52:179–87.

    Article  CAS  PubMed  Google Scholar 

  25. Konradsen JR, Nordlund B, Onell A, Borres MP, Grönlund H, Hedlin G. Severe childhood asthma and allergy to furry animals: refined assessment using molecular-based allergy diagnostics. Pediatr Allergy Immunol. 2014;25:187–92.

    Article  PubMed  Google Scholar 

  26. Mattsson L, Lundgren T, Olsson P, Sundberg M, Lidholm J. Molecular and immunological characterization of can f 4: a dog dander allergen cross-reactive with a 23 kDa odorant-binding protein in cow dander. Clin Exp Allergy. 2010;40:1276–87.

    Article  CAS  PubMed  Google Scholar 

  27. Nilsson OB, Binnmyr J, Zoltowska A, Saarne T, van Hage M, Grönlund H. Characterization of the dog lipocalin allergen can f 6: the role in cross-reactivity with cat and horse. Allergy. 2012;67:751–7.

    Article  CAS  PubMed  Google Scholar 

  28. Uriarte SA, Sastre J. Clinical relevance of molecular diagnosis in pet allergy. Allergy. 2016;71:1066–8.

    Article  CAS  PubMed  Google Scholar 

  29. Apostolovic D, Sánchez-Vidaurre S, Waden K, Curin M, Grundström J, Gafvelin G, et al. The cat lipocalin Fel d 7 and its cross-reactivity with the dog lipocalin can f 1. Allergy. 2016;71:1490–5.

    Article  CAS  PubMed  Google Scholar 

  30. Nordlund B, Konradsen JR, Kull I, Borres MP, Önell A, Hedlin G, et al. IgE antibodies to animal-derived lipocalin, kallikrein and secretoglobin are markers of bronchial inflammation in severe childhood asthma. Allergy. 2012;67:661–9.

    Article  CAS  PubMed  Google Scholar 

  31. Hilger C, Swiontek K, Arumugam K, Lehners C, Hentges F. Identification of a new major dog allergen highly cross-reactive with Fel d 4 in a population of cat- and dog-sensitized patients. J Allergy Clin Immunol. 2012;129:1149–51.

    Article  CAS  PubMed  Google Scholar 

  32. van Hage M, Hilger C. Allergy to cat, dog and horse. In: EAACI molecular allergology user guide. Pediatr Allergy Immunol. 2016;23:123–9.

    Google Scholar 

  33. Min J, Foo ACY, Gabel SA, Perera L, DeRose EF, Pomés A, et al. Structural and ligand binding analysis of the pet allergens can f 1 and Fel d 7. Front Allergy. 2023;4:1133412.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Janssen-Weets B, Kerff F, Swiontek K, Kler S, Czolk R, Revets D, et al. Mammalian derived lipocalin and secretoglobin respiratory allergens strongly bind ligands with potentially immune modulating properties. Front Allergy. 2022;3:958711.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Schoos AM, Chawes BL, Bloch J, Hansen B, Stokholm J, Bønnelykke K, et al. Children monosensitized to can f 5 show different reactions to male and female dog allergen extract provocation: a randomized controlled trial. J Allergy Clin Immunol Pract. 2020;8:1592–7.

    Article  PubMed  Google Scholar 

  36. Liccardi G, Calzetta L, Bilò MB, Brusca I, Cecchi L, Costantino MT, et al. A prevalent exposure to male dog is a risk factor for exclusive allergic sensitization to can f 5: an Italian multicenter study. J Allergy Clin Immunol Pract. 2020;8:2399–401.

    Article  PubMed  Google Scholar 

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Correspondence to Wolfgang Hemmer PhD.

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W. Hemmer declares that he has no competing interests.

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Hemmer, W. How molecular diagnostics help us to correctly identify pet allergies. Allergo J Int 32, 123–129 (2023). https://doi.org/10.1007/s40629-023-00255-8

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