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Basophil activation test for the improved diagnosis of peanut and tree nut allergy.

Marini-Rapoport, O., M. Bhowmik, S.U. Patil, 2025. Basophil activation test for the improved diagnosis of peanut and tree nut allergy. Curr Allergy Asthma Rep 25, 19. https://doi.org/10.1007/s11882-025-01200-1

Purpose of review: As an ex-vivo test of allergic effector cell activation, basophil activation testing (BAT) to allergen enables quantification of the in-vivo IgE-mediated allergic response. BAT thus holds promise in the diagnosis and monitoring of peanut and tree nut allergies. Recent systematic analyses and expert recommendations support a role for BAT in the diagnosis of peanut and tree nut allergy. Recent findings: Diagnostic cut-offs for BAT in peanut and tree nut allergy have been identified. Consistently, BAT can discriminate with high sensitivity and specificity between allergy and tolerance when measured against oral food challenges. Furthermore, the utilization of BAT has can increase the sensitivity and specificity of peanut allergy and tree nut allergy diagnosis, both alone and in conjunction with specific IgE testing and skin prick testing. Summary: BAT is a promising tool in the diagnosis of peanut and tree nut allergy.

Validation of the NUT CRACKER diagnostic algorithm and prediction for cashew and pistachio co-allergy.

Goldberg, M.R., M.Y. Appel, K. Tobi, M.B. Levy, N. Epstein-Rigbi, M. Holmqvist, J. Östling, L. Nachshon, J. Lidholm, A. Elizur, 2024. Validation of the NUT CRACKER diagnostic algorithm and prediction for cashew and pistachio co-allergy. J Allergy Clin Immunol Pract. 12(5):1273-1282.

Background: Because of the high cross-sensitization among tree nuts, the NUT CRACKER (Nut Co-reactivity-Acquiring Knowledge for Elimination Recommendations) study proposed a diagnostic algorithm to minimize the number of required oral food challenges (OFCs). Objective: To validate the algorithm for cashew and pistachio allergy and determine markers for allergic severity. Methods: Patients (n = 125) with a median age of 7.8 (interquartile range, 5.9-11.2) years with suspected tree nut allergy were evaluated prospectively with decision tree points on the basis of skin prick test (SPT), basophil activation test (BAT), and knowledge of the coincidence of allergies. Validation of allergic status was determined by OFC. Markers of clinical severity were evaluated using the combined original and prospective cohort (n = 187) in relationship to SPT, BAT, and Ana o 3-sIgE. Results: Reactivity to cashew in SPT, BAT, and Ana o 3-sIgE and the incidence of abdominal pain on challenge were significantly higher in dual-allergic cashew/pistachio patients (n = 82) versus single cashew allergic patients (n = 18) (P = .001). All 3 diagnostic tests showed significant inverse correlation with log10 reaction doses for positive cashew OFC. The algorithm reduced overall the total number of OFCs by 72.0%, with a positive predictive value and negative predictive value of 93.0% and 99.0%, respectively. Cashew false-positives were observed primarily in hazelnut-allergic patients (P = .026). In this population, Ana o 3-specific IgE could diagnose cashew allergy with a sensitivity of more than 90% and a specificity of more than 95%. Conclusions: The NUT CRACKER diagnostic algorithm was validated and reduced the number of diagnostic OFCs required. Markers for severity phenotypes may guide oral immunotherapy protocols, improving the risk/benefit ratio for patients.

Effects of enzymatic hydrolysis combined with pressured heating on tree nut allergenicity.

Cuadrado, C., C. Arribas, A. Sanchiz, M.M. Pedrosa, P. Gamboa, D. Betancor, C. Blanco, B. Cabanillas, R. Linacero, 2024.  Effects of enzymatic hydrolysis combined with pressured heating on tree nut allergenicity. Food Chem. 451:139433. https://doi.org/10.1016/j.foodchem.2024.139433

Hazelnut, pistachio and cashew are tree nuts with health benefits but also with allergenic properties being prevalent food allergens in Europe. The allergic characteristics of these tree nuts after processing combining heat, pressure and enzymatic digestion were analyzed through in vitro (Western blot and ELISA) and in vivo test (Prick-Prick). In the analyzed population, the patients sensitized to Cor a 8 (nsLTP) were predominant over those sensitized against hazelnut seed storage proteins (Sprot, Cor a 9 and 14), which displayed higher IgE reactivity. The protease E5 effectively hydrolyzed proteins from hazelnut and pistachio, while E7 was efficient for cashew protein hydrolysis. When combined with pressured heating (autoclave and Controlled Instantaneous Depressurization (DIC)), these proteases notably reduced the allergenic reactivity. The combination of DIC treatment before enzymatic digestion resulted in the most effective methodology to drastically reduce or indeed eliminate the allergenic capacity of tree nuts.

Identification of new allergens in macadamia nut and cross-reactivity with other tree nuts in a Spanish cohort.

Gutiérrez-Díaz, G., D. Betancor, J. Parrón-Ballesteros, R.G. Gordo, E.S. Castromil-Benito, E. Haroun, M. Vázquez de la Torre, J. Turnay, M. Villalba, J. Cuesta-Herranz, C. Pastor-Vargas, 2024. Identification of new allergens in macadamia nut and cross-reactivity with other tree nuts in a Spanish cohort. Nutrients. 16(7):947. https://doi.org/10.3390/nu16070947

The consumption of macadamia nuts has increased due to their cardioprotective and antioxidant properties. However, this rise is consistent with an increase in the cases of macadamia nut allergy, leading to severe reactions. Although two Macadamia integrifolia allergens (Mac i 1 and Mac i 2) have been identified in Australian and Japanese patients, the allergenic sensitization patterns in Western European populations, particularly in Spain, remain unclear. For this purpose, seven patients with macadamia nut allergy were recruited in Spain. Macadamia nut protein extracts were prepared and, together with hazelnut and walnut extracts, were used in Western blot and inhibition assays. IgE-reactive proteins were identified using MALDI-TOF/TOF mass spectrometry (MS). Immunoblotting assays revealed various IgE-binding proteins in macadamia nut extracts. Mass spectrometry identified three new allergens: an oleosin, a pectin acetylesterase, and an aspartyl protease. Cross-reactivity studies showed that hazelnut extract, but not walnut extract, inhibited macadamia nut oleosin-specific IgE binding. This suggests that oleosin could be used as marker for macadamia-hazelnut cross-reactivity. The results show an allergenic profile in the Spanish cohort different from that previously detected in Australian and Japanese populations. The distinct sensitization profiles observed highlight the potential influence of dietary habits and environmental factors exposure on allergenicity.