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Walnut allergy across Europe: sensitization patterns and prediction of severity

Published online: September 7, 2020

Walnut is one of the tree nuts most often linked to potentially severe food allergic reactions in Europe and worldwide. Based on the data collected during the EuroPrevall population studies, we know that up to 10% of the general population in some European regions has IgE antibodies to walnut extract. Ongoing developments in food allergy diagnostic testing make it possible to assess IgE sensitization to a broadening spectrum of specific food allergen components, commonly referred to as component-resolved diagnostics (CRD). Relatively little is known regarding IgE sensitization to specific walnut components in different parts of Europe, and their clinical relevance.

In a study recently published in The Journal of Allergy and Clinical Immunology: In Practice, Lyons et al. used data from the EuroPrevall outpatient project in children and adults to elucidate geographical differences in IgE sensitization to 7 walnut components in 12 countries across Europe, and to investigate which clinical and serological variables are related to severity of walnut allergy. A total of 531 individuals reporting symptoms within 2 hours of ingestion of walnut underwent a fully standardized clinical evaluation. This evaluation included an extensive questionnaire on reaction characteristics and clinical background, skin prick testing with walnut extract, and blood testing by ImmunoCAP with walnut extract. Sensitization to specific walnut allergen components was assessed by ImmunoCAP in 202 participants.

The researchers found clear geographical differences in walnut component sensitization patterns across Europe. The 3 most common sensitizing walnut components were Jug r 5 (58% of individuals reporting symptoms to walnut), Jug r 7 (23%) and Jug r 3 (14%). Jug r 5 is a PR-10 protein that cross-reacts with birch pollen, and was therefore particularly dominant in birch endemic Northern and Central Europe. Jug r 7 is a profilin type walnut component that can cross-react with any pollen, as a result of which sensitization to Jug r 7 was observed frequently throughout Europe. Jug r 3 is a lipid transfer protein, to which sensitization may be primary (non-cross-reactive) or the result of cross-reactivity with certain foods (especially peach) or possibly pollen (e.g., mugwort or plane tree).  Sensitization to Jug r 3 was found mostly in Southern Europe. Sensitization to walnut storage proteins (Jug r 1, 2, 4 and 6) was detected in up to 10% of subjects, most frequently in the Netherlands and Spain. Severity of walnut allergy was best predicted by a combination of the following variables: symptoms elicited by skin contact with walnut, ever having atopic dermatitis, family history of atopic disease, mugwort pollen allergy, sensitization to cat and/or dog, a positive prick test to walnut extract, and IgE to Jug r 1, Jug r 5, Jug r 7 or cross-reactive carbohydrate determinants. This model attained good predictive accuracy, as expressed by an AUC of 0.81, and performed significantly better than walnut CRD, extract-based testing, or clinical background alone.

In summary, the distribution of sensitization to walnut components across Europe follows a pattern similar to other plant source foods and is considerably influenced by cross-reactivity with pollen. Walnut CRD can help predict severity of walnut allergy, particularly when considered in combination with results from extract-based testing and clinical background.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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