The first reptilian allergen and major allergen for fish-allergic patients: Crocodile β-parvalbumin

Pediatr Allergy Immunol. 2022 May;33(5):e13781. doi: 10.1111/pai.13781.


Background: Clinical cross-reactivity between bony fish, cartilaginous fish, frog, and chicken muscle has previously been demonstrated in fish-allergic patients. In indicative studies, two reports of anaphylaxis following the consumption of crocodile meat and IgE-cross-binding were linked to the major fish allergen parvalbumin (PV). This study investigates IgE-binding proteins in crocodile meat with a focus on PV and their clinical relevance.

Methods: Proteins were extracted from muscle tissue of crocodile, three bony fish, and two cartilaginous fish. A cohort of fish-allergic pediatric patients (n = 77) underwent allergen skin prick testing (SPT) to three fish preparations (n = 77) and crocodile (n = 12). IgE-binding proteins were identified and quantified by SDS-PAGE, mass spectrometric analyses, and immunoblotting using commercial and in-house antibodies, as well as individual and pooled patients' serum. PV isoforms were purified or recombinantly expressed before immunological analyses, including human mast cell degranulation assay.

Results: Of the tissues analyzed, PV was most abundant in heated crocodile preparation, triggering an SPT of ≥3 mm in 8 of 12 (67%) fish-allergic patients. Seventy percent (31 of 44) of fish PV-sensitized patients demonstrated IgE-binding to crocodile PV. Crocodile β-PV was the major IgE-binding protein but 20-fold less abundant than α-PV. Cellular reactivity was demonstrated for β-PV and epitopes predicted, explaining frequent IgE-cross-binding of β-PVs. Both PV isoforms are now registered as the first reptile allergens with the WHO/IUIS (β-PV as Cro p 1 and α-PV as Cro p 2).

Conclusion: Fish-allergic individuals may be at risk of an allergy to crocodile and should seek specialist advice before consuming crocodilian meat.

Keywords: allergy diagnosis and management; component-resolved diagnostics; cross-reactivity; fish allergy; food allergy; reptile; skin prick testing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens
  • Alligators and Crocodiles*
  • Animals
  • Child
  • Cross Reactions
  • Fishes
  • Food Hypersensitivity* / diagnosis
  • Humans
  • Immunoglobulin E
  • Parvalbumins


  • Allergens
  • Parvalbumins
  • Immunoglobulin E