Human Allergogeneticists Should Listen to Their Dog’s Barking

  • A. L. de Weck
  • M. Griot-Wenk
  • H. Schneider
  • B. Schiessl
  • B. Zeemann
  • P. Mayer
  • E. Liehl

Abstract

A colony of Beagle dogs was used within the last 6 years to develop an allergie dog model. The dogs were sensitized to various allergens, such as recombinant Betvi (birch) and Phi p5 (timothy), ovalbumin, peanut and many others. The first observation was that dogs clearly segregated into high and low IgE responder dogs when immunized for the first time by intradermal or subcutaneous injections of allergen within l month of birth. Characteristic for the high IgE response was the possibility to boost it at any time later in life and to extend it later to other allergens, like is usually the case in atopic man. Low IgE responder dogs showed a low response which was not boostable and could not be extended to other allergens later on. Numerous breeding experiments over 5 years demonstrated clearly that the high IgE response is inherited as a dominant trait.

However, it was then found that this trait does not express itself if first immunization of high IgE responders occurs later than the 3rd month of life. In that case, a potent suppressor mechanism for IgE takes over and the animal presents phenotypically later as a low IgE responder. The mode of sensitization is also crucial for later phenotypic expression. Sensitization by inhalation to the same allergens is obviously regulated by some additional gene(s) since only part of the high IgE responder litters may be sensitized by inhalation. A similar phenomenon was observed in the spontaneous occurrence of IgE to house dust mites or pollens in the dog colony.

These results show clearly that genetic studies based, like is still the case in man, on the spontaneous occurrence of IgE responses to ubiquitous allergens and phenotypes detected long after birth would lead to entirely wrong genetic conclusions.

Keywords

Dust Europe Hydroxide Flare Posite 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Coca A., Cooke R.A. On the classification of the phenomena of hypersensitiven ess. J. Immunology, 8:163–182,1923Google Scholar
  2. 2.
    Coca A., Grove E.R Studies in hyper sensitiven ess. XIII. A study of atopic reagins. J. Immunol., 10:445–464,1925Google Scholar
  3. 3.
    Katz D.H. The allergie phenotype: Manifestation of ‘allergic breakthrough’ and imbalance or normal ‘damping’of IgE production. Immunol. Rev. 41:77–104,1978PubMedCrossRefGoogle Scholar
  4. 4.
    Holgate S.T., Wahn U. The genetics of atopy and asthma Clin. Exp. Allergy 29(Suppl.4):1–59,1999Google Scholar
  5. 5.
    Cookson W.O.C.M. Genetic aspects of atopy. In Epidemiology of Clinical Allergy (Burrm L. Ed), Monographs in Allergy, Karger, Basle, 31:171–189,1993Google Scholar
  6. 6.
    Marsh D.G. Genetic studies of IgE responsiveness and asthma. In ‘From Genetics to Quality of Life’ (Chanes R, Bousquet J., Michel F.B., Godard R Eds) Hogrefe&Huber, Göttingen, 1996, pp. 9–14Google Scholar
  7. 7.
    Hopkin J.M., Shirakawa T. The genetics of atopy. In ‘Prediction and Prevention of Childhood Allergy’ (Sasaki S., Miyamoto T., Hopkin J.M. Eds) Churchill-Livingstone, Osaka, 1995, pp 7–15Google Scholar
  8. 8.
    Wilkinson J., Thomas N.S., Morton N., Hvnolgate S.T. Candidate gene and mutational analysis in asthma and atopy. Int. Arch. Allergy Immunol. 118:265–267,1999PubMedCrossRefGoogle Scholar
  9. 9.
    Marsh D.G., Neely J.D., Breaseale D.R. et al. Linkage analysis of IL-4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. Science, 264:1152–1156 1994PubMedCrossRefGoogle Scholar
  10. 10.
    de Week A.L., Derer M., Mayer P., Stumper B., Schöni B., Haemmerling R,, Kristensen R, Itaya H., Yamasita Y., Hasegawa A. Perspectives of diagnostics of canine allergies—a new serologie method for determination of allergen-specific IgE with strip tests. Prakt. Tierarzt, 79:6–23,1998Google Scholar
  11. 11.
    de Weck A.L. What can we learn from the allergie zoo? Int. Arch. Allergy Immunol., 107,13–18, 1995PubMedCrossRefGoogle Scholar
  12. 12.
    de Week A.L, Derer M., Mayer P., Stumper B. Allergy starts early in life: clinical and experimental evidence. In ‘Prediction and Prevention of Childhood Allergy’ (Sasaki S., Miyamoto T., Hopkin J.M. Eds) Churchill-Livingstone, Osaka, 1995, pp 181–197Google Scholar
  13. 13.
    Schiessl B., de Weck A.L., Hodgkin-Pickart L., Zuni M., Zemann B., Mayer P., Liehl E. Importance of early allergen contact for the development of sustained immunoglobulin E response in Beagle dogs. Clin. Exp. Allergy, submittedGoogle Scholar
  14. 14.
    Ricci M., Rossi O., Bertoni M., Mvnatucci A. The importance of Tl12-like cells in the pathogenesis of of airway allergie inflammation. Clin. Exp. Allergy 23:360–369,1993PubMedCrossRefGoogle Scholar
  15. 15.
    Romagnani S. Induction of Thi and TI12 responses: a key role for the ‘natural’ immune response? Immunol. Today 13:379–381,1992PubMedCrossRefGoogle Scholar
  16. 16.
    de Week A.L. Food allergy, problems, fiction and hard facts. In ‘Highlights in Food Allergy’ (Wühtrich B., Ortolani C, Eds) Karger, Basel,1998, pp 1–8Google Scholar
  17. 17.
    Holt P.G., McMenamin D., Nelson D. Ptimary sensitization to inhalant allergens during infancy. Pediatr. Allergy Immunol. 1:3–13,1990CrossRefGoogle Scholar
  18. 18.
    Zemann B., Griot-Wenk M.E., Schiessl B.,Nefzger M., Mayer P., Liehl E, Schneider H., de Week A.L. Induction of primary IgE oral tolerance to bb-lactoglobulin in an allergie dogmodel. Clin. Exp. Allergy, submittedGoogle Scholar
  19. 19.
    Bocks A., Atkins RM. The natural history of peanut allergy. J. Allergy Clin. Immunol. 83:900–904,1989CrossRefGoogle Scholar
  20. 20.
    Shirakawa T., Enornoto T., Shimazu S., Hopkin J.M. The inverse association between tuberculin responses and atopic disorders. Science, 275:77–79,1997PubMedCrossRefGoogle Scholar
  21. 21.
    Umetsu D. Protective immunity in asthma and allergy. Congress Swiss Society of Allergology and Immunology, Lausanne, April 2001Google Scholar
  22. 22.
    de Weck A.L., Mayer P., Stumper B., Schiessl B., Pickart L. Dog allergy, a model for allergy genetics. Int. Arch. Allergy Immunol. 113:55–57,1997PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • A. L. de Weck
  • M. Griot-Wenk
  • H. Schneider
  • B. Schiessl
  • B. Zeemann
  • P. Mayer
  • E. Liehl

There are no affiliations available

Personalised recommendations