Albumins represent highly cross-reactive animal allergens

Front Immunol. 2023 Oct 20:14:1241518. doi: 10.3389/fimmu.2023.1241518. eCollection 2023.


Albumins from animals are highly cross-reactive allergens for patients suffering from immunoglobulin E (IgE)-mediated allergy. Approximately 20-30% of cat and dog allergic patients show IgE reactivity and mount IgE-mediated allergic reactions to cat and dog albumin. It is astonishing that allergic patients can develop specific IgE responses against animal albumins because these proteins exhibit a more than 70% sequence identity to human serum albumin (HSA) which is the most abundant protein in the blood of the human body. The sequence identity of cat albumin (Fel d 2) and dog albumin (Can f 3) and HSA are 82% and 80%, respectively. Given the high degree of sequence identity between the latter two allergens and HSA one would expect that immunological tolerance would prohibit IgE sensitization to Fel d 2 and Can f 3. Here we discuss two possibilities for how IgE sensitization to Fel d 2 and Can f 3 may develop. One possibility is the failed development of immune tolerance in albumin-allergic patients whereas the other possibility is highly selective immune tolerance to HSA but not to Fel d 2 and Can f 3. If the first assumption is correct it should be possible to detect HSA-specific T cell responses and HSA-containing immune complexes in sensitized patients. In the latter scenario few differences in the sequences of Fel d 2 and Can f 3 as compared to HSA would be responsible for the development of selective T cell and B cell responses towards Fel d 2 as well as Can f 3. However, the immunological mechanisms of albumin sensitization have not yet been investigated in detail although this will be important for the development of allergen-specific prevention and allergen-specific immunotherapy (AIT) strategies for allergy to albumin.

Keywords: albumin; allergen; allergy; antibody; cross-reactivity; epitope; immunoglobulin E (IgE); tolerance.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins*
  • Allergens
  • Animals
  • Cats
  • Dogs
  • Humans
  • Hypersensitivity*
  • Immunoglobulin E
  • Serum Albumin, Human


  • Albumins
  • Allergens
  • Immunoglobulin E
  • Serum Albumin, Human

Grants and funding

Funded by the Danube Allergy Research Cluster program of the Country of Lower Austria, the review of albumin-specific IgE cross-reactivity was supported by a grant of the Russian Science Foundation (the Project: No: 23-75-30016: “Allergen micro-array-based assessment of allergic sensitization profiles in the Russian Federation as a basis for personalized treatment and prevention of allergy (AllergochipRUS)”), by Worg Pharmaceuticals, Hangzhou, China and by the Megagrant of the Government of the Russian Federation, grant number 075-15-2021-632 (14.W03.31.0024). The funder was not involved in the study design, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.