Allergen

Summary

Cor a 16 was identified in 2022 as a vicilin-like 7S globulin from Corylus avellana. It belongs to the same protein family as Cor a 11 but features an extended N-terminal region which undergoes proteolytic processing, yielding multiple IgE-binding fragments. Cor a 16 extends the family of hazelnut vicilins and may explain complex IgE responses in hazelnut-sensitized patients.

Epidemiology

Cor a 16 appears as a major allergen to which approximately 80% of hazelnut-sensitized paediatric sera (n=106) from the US were sensitized, with IgE levels ranging up to over 100 kU_A/L. Twenty of the 106 samples (19%) tested positive for one of the two vicilins Cor a 11 and Cor a 16, but negative for the other. Of these 20 samples, 18 were uniquely positive to Cor a 16 and 2 to Cor a 11 (Mattsson 2022).

Environmental Characteristics

Source and Tissue

The gene for Cor a 16 has been identified in the genomes of four Corylus species (Amoroso 2025). Cor a 16 is a seed storage protein from which multiple small, IgE-reactive fragments are generated by proteolytic processing during seed maturation. The N-and C-terminal parts of Cor a 16 have been recombinantly expressed and purified (Mattsson 2022).

Risk Factors

Risk factors include atopic predisposition, sensitization to Cor a 11, Cor a 9, Cor a 14 and Cor a 16 among children (Mattson 2022) and adults (Elizur 2025), and cross-reactivity with vicilins from walnut, peanut, or cashew (Barre 2008).

Clinical Relevance

Cor a 16 fragments maintain IgE activity and may explain complex IgE responses in hazelnut-sensitized patients.

Diagnostic Relevance

Recombinant Cor a 16 is available for in vitro IgE testing, enhancing identification of primary hazelnut allergy. Combined measurement of IgE to Cor a 9, 11, 14, and 16 may improve sensitivity and accuracy of risk assessment (Mattsson 2022, Elizur 2025).

Prevention and Therapy

There is currently no regulatory approved hazelnut component oral immunotherapy available. Management relies on avoidance, food labelling vigilance, and when indicated, adrenaline auto-injector prescription. A clinical study of hazelnut oral immunotherapy, involving patients predominantly sensitized to Cor a 9, Cor a 14, and Cor a 16, demonstrated effective desensitization and a concomitant decrease in IgE to Cor a 16 (Elizur 2025).

Molecular Aspects

Cor a 16 is a cupin-fold 7S globulin (vicilin) of ~480 amino acids forming trimeric assemblies. The N-terminal region contains labile bonds generating 20–30 kDa allergenic fragments (Mattsson 2022).

The complete Cor a 16 allergen (Cor a 16.0101) and two subsegments, corresponding to amino acids 29-714 and 715-1133, are listed in the WHO/IUIS Allergen Nomenclature Sub-Committee database.

Cross-reactivity

Cor a 16 belongs to the same protein family as Cor a 11 but features an extended N-terminal region that undergoes proteolytic processing during protein maturation, yielding multiple IgE-binding fragments. Cor a 16 share similarities with segments in the N-terminal region of vicilin-like proteins from macadamia, walnut and pecan, however there are limited cross-reactivity data available for Cor a 16 (Mattson 2022).

Exposure

It is likely that Cor a 16 and its fragments persist after roasting, baking, and digestion, remaining allergenic in trace amounts within processed or composite foods (Holzhauser 2000).

Explained Results

Allergen information

Cor a 16 is a recently identified 7S globulin (vicilin) featuring an N-terminal region subject to proteolytic processing, yielding multiple IgE-binding fragments.

Clinical relevance

Cor a 16 extends the family of hazelnut vicilins and may explain complex IgE responses in hazelnut-sensitized patients.

Cross-reactivity

Cor a 16 is related in structure to Cor a 11 and shares similarities with segments in the N-terminal region of vicilin-like proteins from macadamia, walnut and pecan. However, there are limited cross-reactivity data available for Cor a 16.

Compiled by Dr. Michael Spangfort

Reviewed by Dr. Jonas Lidholm, November 2025