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Updated: Sep 19, 2026
Basophil Activation Test for Allergy Diagnosis
Published on: May 31, 2021
Rate and Predictors of Hazelnut Cross-Desensitization Following Walnut Oral Immunotherapy (Nut CRACKER Study)
Arnon Elizur1, Yael Koren1, Michael Y Appel2
1Institute of Allergy, Immunology and Pediatric Pulmonology, Yitzhak Shamir Medical Center, Be'er Ya'akov, Israel; Department of Pediatrics, Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Background:
The potential of walnut oral immunotherapy (OIT) to cross-desensitize for hazelnut has been anecdotally reported.
Objective:
To identify rates and predictors of hazelnut cross-desensitization following walnut OIT.
Methods:
A prospective cohort study was conducted in the Institute of Allergy at the Shamir Medical Center between July 2016 and July 2021. The rate of hazelnut cross-desensitization in walnut-hazelnut coallergic patients aged 4 years or older following walnut OIT was compared with hazelnut allergy resolution in observational controls. Immunologic markers at baseline and following walnut desensitization were examined, and clinical and molecular predictors of cross-desensitization were sought.
Results:
Hazelnut cross-desensitization occurred in 53 of 99 (53.5%) patients who began walnut OIT, and in 53 of 80 (66.2%) walnut-desensitized patients challenged for hazelnut, compared with 3 of 19 (15.8% resolution rate) controls (odds ratio [OR], 6.1, 95% CI, 1.7-22.4, P = .003, and OR, 10.5, 95% CI, 2.8-39.1, respectively). Immunologic desensitization (decreased hazelnut sensitization and basophil reactivity, and increased specific IgG4) followed. On multivariate analysis, a higher hazelnut skin prick test wheal diameter (OR, 1.28, 95% CI, 1.07-1.54, P = .008) and a hazelnut reaction dose of 60 mg or less (OR, 8.3, 95% CI, 2.0-34.5, P = .003) at baseline predicted persistent hazelnut allergy. Baseline specific IgE levels greater than or equal to 7 kUA/L to Cor a 14, but not to Cor a 9 and 16, were associated with persistent hazelnut allergy. Cor a 14-specific IgG4 significantly increased only in cross-desensitized patients, whereas Cor a 9- and Cor a 16-specific IgG4 increased in persistent hazelnut-allergic patients, as well.
Conclusions:
Most walnut-hazelnut-allergic patients benefit from single walnut OIT. Lower hazelnut sensitization and a higher reaction dose predict cross-desensitization. Cor a 14 plays a role in persistent hazelnut allergy.
