Walnut and hazelnut coallergy is a frequent manifestation in clinical practice whose molecular basis remains unclear. For this purpose, walnut-hazelnut cross-reactivity was evaluated in 20 patients allergic to one or both tree nuts and sensitized to their 2S albumins. Immunoblotting assays showed that 85% of patients recognized Jug r 1, walnut 2S albumin, which was associated with the development of severe symptoms; 50% of them corecognized hazelnut 2S albumin, Cor a 14. Both allergens were isolated using chromatographic techniques. Inhibition ELISAs revealed that Jug r 1 strongly inhibited the binding of Cor a 14-specific IgE, but Cor a 14 only partially inhibited Jug r 1-specific IgE binding. Our results showed that patients sensitized to walnut/hazelnut 2S albumins were not a homogeneous population. There were patients sensitized to specific epitopes of walnut 2S albumins and patients sensitized to cross-reactive epitopes between walnut and hazelnut, with Jug r 1 being the primary sensitizer.

This study reports on the interactions of egg proteins, which represent a major health concern in food allergy, with polyphenols obtained from orange and lemon peels. The antioxidant properties of such citrus peel extracts prior to protein binding were evaluated. The resulting edible, and therefore inherently safe, matrices exhibit reduced IgE binding compared to pure proteins in indirect immunological assays (ELISA) using individual sera from patients allergic to ovalbumin and lysozyme. The reduced allergenicity could arise from the interactions with polyphenols, which alter the structure and functionality of the native proteins. It is hypothesized that the anti-inflammatory and antioxidant properties of the polyphenols, described as inhibitors of the allergic response, could add immunomodulatory features to the hypoallergenic complexes. A docking analysis using lysozyme was conducted to scrutinize the nature of the protein–polyphenol interactions. An in silico study unravelled the complexity of binding modes depending on the isoforms considered. Altogether, the presented results validate the antioxidant properties and reduced allergenicity of polyphenol-fortified proteins. Lastly, this study highlights the upgrading of vegetable wastes as a source of natural antioxidants, thus showing the benefits of a circular economy in agri-food science.

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.

This study describes a potent hypoallergenic casein–polyphenol formula based on preclinical assays of serum samples from patients allergic to cow’s milk proteins. Despite some variability among patients, results showed a significant IgE-binding reduction. This proof of concept indicates the reliability of altering the native structure and potential epitopes of allergens by natural polyphenols, consistent with previous studies monitoring amide bonding by vibrational spectroscopy. Structural predictions, binding pocket scouting, and molecular docking were used to explore the nature of the binding between polyphenols and casein isoforms. In silico modeling identified the interaction of polyphenol–protein hybrids with IgE-binding epitopes in α-S1, α-S2, and β-caseins, albeit only one in κ-casein, which provides a molecular basis for the clinically observed hypoallergenicity. Overall, preclinical analysis holds promise for oral immunotherapy to end food sensitivity and reduce the risk of life-threatening anaphylaxis. Parallel bioassays, however, with β-lactoglobulin, another cow’s milk allergen, afforded promising results.