Identification and isolation of a Fel d 1-like molecule as a major rabbit allergen

J Allergy Clin Immunol. 2014 Mar;133(3):759-66. doi: 10.1016/j.jaci.2013.04.034. Epub 2013 Jun 12.


Background: Rabbits are increasingly kept as domestic pets. Several rabbit allergens have been characterized. However, their sequences are still elusive, and none of these molecules are available for diagnosis.

Objective: We sought to isolate major allergens from the rabbit Oryctolagus cuniculus and to investigate their importance in sensitized patients.

Methods: Proteins were extracted from rabbit hair, and IgE-reactive proteins were purified by using sequential chromatography. Allergens were characterized by means of N-terminal sequencing and mass spectrometry. IgE reactivity to a new allergen was analyzed in sera of 35 patients sensitized to rabbits in a domestic setting. A model of the crystal structure of the isolated proteins was constructed.

Results: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. The molecule that belongs to the secretoglobin family is a heterodimer of 18 to 19 kDa composed of 2 polypeptide chains, CL2 and AL. CL2 has a predicted N-linked glycosylation site confirmed by using mass spectrometry. Of the 35 patients with rabbit allergy studied, 27 (77%) had IgE to both the glycosylated and deglycosylated Ory c 3 heterodimer. Allergenicity of Ory c 3 was confirmed by using skin prick tests and the basophil activation assay. Modeling of the structure revealed a marked homology to Fel d 1, the major cat allergen. However, no IgE cross-reactivity was detected between Fel d 1 and Ory c 3.

Conclusion: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. After Fel d 1, Ory c 3 is the second mammalian secretoglobin shown to be a major allergen.

Keywords: Allergen; Fel d 1; IgE; Ory c 3; cross-reactivity; inhibition; lipophilin; molecular modeling; rabbit; secretoglobin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allergens / chemistry
  • Allergens / immunology
  • Allergens / isolation & purification*
  • Amino Acid Sequence
  • Animals
  • Cats
  • Child
  • Child, Preschool
  • Cross Reactions
  • Female
  • Glycoproteins / chemistry
  • Glycoproteins / immunology
  • Glycoproteins / isolation & purification*
  • Humans
  • Immunoglobulin E / immunology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Rabbits / immunology*


  • Allergens
  • Glycoproteins
  • Ory c 3 allergen, Oryctolagus cuniculus
  • Immunoglobulin E
  • Fel d 1 protein, Felis domesticus