The Editor recommends this issue's articles to the reader

doi:10.1111/pai.12332

2014-12-01 00:00:00

Effect of heat treatment on milk and egg proteins allergenicity Heating destroys many conformational epitopes and reduces allergenicity of some foods. IgE‐epitope binding has been shown to be different among patients who outgrew their cow's milk or hen's egg allergy and among those who had persistent allergy. A significant proportion of milk and egg allergic children can tolerate these foods in their baked forms, for example muffins or cupcakes. Bloom et al. sought to explore the effects of heating on milk and egg proteins and to evaluate for differences in immune‐labeling among children regarding reactivity to heated milk or egg. They tested sera obtained from children participating in the clinical dietary intervention trials in which the status of their reactivity to baked milk or egg was determined with an oral food challenge. Milk and egg samples were variably heated and prepared, at times within a wheat matrix. Sodium dodecyl sulfate (SDS)‐polyacrylamide gel electrophoresis (PAGE), protein transfer, and Western blot were performed with sera from 20 milk‐ and 24 egg‐allergic children. Gel electrophoresis showed strongly staining casein bands that persisted for up to 60 min of boiling. In contrast, β‐lactoglobulin and α‐lactalbumin bands became progressively weaker with increasing heating times, with no detectable β‐lactoglobulin after 15–20 min of heating. In the hen's egg, the ovalbumin band became progressively weaker, whereas ovomucoid remained stable after 25 min of heating. Immuno‐labeling revealed that all heated milk‐reactive children possessed IgE antibodies that bound the casein fraction regardless of heating time. The presence of wheat during heating resulted in decreased IgE antibody binding to milk and egg white proteins. Heating has a different effect on whey and caseins in milk and ovalbumin and ovomucoid in egg white. The effect of heat on protein allergenicity is influenced by the temperature and duration of heating. The bioavailability of heated proteins is further decreased in the presence of wheat. These findings add to our understanding of the different phenotypes of milk and egg allergy. Katherine A. Bloom An observational, real‐life safety study of a 5‐grass‐pollen sublingual tablet in children Allergen immunotherapy is a disease‐modifying treatment option for qualified patients with allergic rhinoconjunctivitis (AR). Although both subcutaneous and sublingual immunotherapies are safe and effective, the convenience of sublingual administration has contributed to increased use of drop or tablet formulations in children. The efficacy and safety of pre‐ and co‐seasonal administration of a 300 index of reactivity (IR) five‐grass pollen sublingual tablet in AR has been demonstrated in double‐blind, placebo‐controlled clinical trials in Europe and North America and in children, adolescents and adults. Accordingly, the tablet first gained marketing approval in Europe in 2008. However, it is always preferable to confirm a medication's efficacy and safety in ‘real‐life’ clinical practice. The multicentre, prospective, open‐label, observational study performed in Germany by Eberle et al. sought to provide the first confirmation of the ‘real‐life’ safety and tolerability of pre‐ and co‐seasonal administration of the 300 IR 5‐grass tablet in children and adolescents (aged 5–17) with physician‐diagnosed AR and sensitization to grass or rye pollen. 207 physicians recruited 849 patients, 829 of whom were treated (mean ± s.d. age: 10.9 ± 3.3). After a short initiation/up‐dosing phase, the patients took the tablet daily for 4 months before the grass pollen season and then throughout the season. Adverse events (AEs) were noted during study visits and consultations, and any AEs possibly related to the tablet (in the physician's opinion) were considered to be adverse drug reactions (ADRs). The fully documented safety analysis set comprised 796 patients, only 9.2% of whom terminated the study for reasons related to AEs. A total of 867 AEs were recorded, and 596 of these were classified as ADRs; the most common were throat irritation (19.1%), oral paresthesia (8.2%), oral pruritus (6.5%) and oedema mouth 213 (6.2%). Importantly, 78.2% of the ADRs were mild or moderate, and no adrenaline use was recorded. In conclusion, Eberle et al.'s detailed post‐marketing study has provided the first ‘real‐life’ confirmation of the good safety profile observed during clinical development of the 300 IR 5‐grass pollen sublingual tablet. Peter Eberle Preventive sublingual immunotherapy in preschool children: first evidence for safety and pro‐tolerogenic effects How can the spread of new sensitizations at a young age and the development of allergies thereafter be stopped? Large birth cohort studies have revealed how a clinically healthy newborn becomes sensitized initially to one and later to many allergens before possibly ending up clinically allergic. Different interventional approaches aim to interrupt this development in an early phase. As one approach, allergen‐specific immunotherapy, as used in allergic children, could withhold an IgE‐sensitization from spreading. In this study, Szépfalusi et al. focused on an earlier age period, before children would have developed a defined allergic disease. Children, 2–5 years old (n = 31), were sensitized to either grass pollen or house dust mites but did not show allergen‐specific symptoms. They received sublingually an allergen‐specific immunotherapy extract (n = 15) or placebo (n = 16) according to their sensitization profile and were treated for 2 years. The primary outcome parameter was a reduction of new sensitizations by sublingual immunotherapy. The authors could neither see a decrease nor an increase of IgE‐sensitization in the verum‐treated group as compared to placebo (as measured by Skin Prick Test, IgE ImmunoCAP, IgE micro array). The authors also assessed immunological parameters, and here, most strikingly, they could observe a significant increase of allergen‐specific IgG to house dust mite (p < 0.05). More specifically, an IL10‐dependent inhibition of allergen‐specific T cell proliferation (p < 0.05) was observed in the treatment group but not in the placebo group. Although this study is of pilot character (n = 31) and thus cannot reveal whether IgE‐sensitization‐spreading can effectively be modified by early (secondary preventive) allergen‐specific immunotherapy, it nevertheless supports that the application mode (sublingual) can effectively and safely be applied to small children of age 2–4 years and most importantly leads to a remarkable pro‐tolerogenic immune‐modulation. Thus, this approach of preventive SLIT deserves more focus in larger trials with adapted allergen sources. Zsolt Szépfalusi

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Pediatric Allergy and Immunology Wiley

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$Effect of heat treatment on milk and egg proteins allergenicity Heating destroys many conformational epitopes and reduces allergenicity of some foods. IgE‐epitope binding has been shown to be different among patients who outgrew their cow's milk or hen's egg allergy and among those who had persistent allergy. A significant proportion of milk and egg allergic children can tolerate these foods in their baked forms, for example muffins or cupcakes. Bloom et al. sought to explore the effects of heating on milk and egg proteins and to evaluate for differences in immune‐labeling among children regarding reactivity to heated milk or egg. They tested sera obtained from children participating in the clinical dietary intervention trials in which the status of their reactivity to baked milk or egg was determined with an oral food challenge. Milk and egg samples were variably heated and prepared, at times within a wheat matrix. Sodium dodecyl sulfate (SDS)‐polyacrylamide gel electrophoresis (PAGE), protein transfer, and Western blot were performed with sera from 20 milk‐ and 24 egg‐allergic children. Gel electrophoresis showed strongly staining casein bands that persisted for up to 60 min of boiling. In contrast, β‐lactoglobulin and α‐lactalbumin bands became progressively weaker with increasing heating times, with no detectable β‐lactoglobulin after 15–20 min of heating. In the hen's egg, the ovalbumin band became progressively weaker, whereas ovomucoid remained stable after 25 min of heating. Immuno‐labeling revealed that all heated milk‐reactive children possessed IgE antibodies that bound the casein fraction regardless of heating time. The presence of wheat during heating resulted in decreased IgE antibody binding to milk and egg white proteins. Heating has a different effect on whey and caseins in milk and ovalbumin and ovomucoid in egg white. The effect of heat on protein allergenicity is influenced by the temperature and duration of heating. The bioavailability of heated proteins is further decreased in the presence of wheat. These findings add to our understanding of the different phenotypes of milk and egg allergy. Katherine A. Bloom An observational, real‐life safety study of a 5‐grass‐pollen sublingual tablet in children Allergen immunotherapy is a disease‐modifying treatment option for qualified patients with allergic rhinoconjunctivitis (AR). Although both subcutaneous and sublingual immunotherapies are safe and effective, the convenience of sublingual administration has contributed to increased use of drop or tablet formulations in children. The efficacy and safety of pre‐ and co‐seasonal administration of a 300 index of reactivity (IR) five‐grass pollen sublingual tablet in AR has been demonstrated in double‐blind, placebo‐controlled clinical trials in Europe and North America and in children, adolescents and adults. Accordingly, the tablet first gained marketing approval in Europe in 2008. However, it is always preferable to confirm a medication's efficacy and safety in ‘real‐life’ clinical practice. The multicentre, prospective, open‐label, observational study performed in Germany by Eberle et al. sought to provide the first confirmation of the ‘real‐life’ safety and tolerability of pre‐ and co‐seasonal administration of the 300 IR 5‐grass tablet in children and adolescents (aged 5–17) with physician‐diagnosed AR and sensitization to grass or rye pollen. 207 physicians recruited 849 patients, 829 of whom were treated (mean ± s.d. age: 10.9 ± 3.3). After a short initiation/up‐dosing phase, the patients took the tablet daily for 4 months before the grass pollen season and then throughout the season. Adverse events (AEs) were noted during study visits and consultations, and any AEs possibly related to the tablet (in the physician's opinion) were considered to be adverse drug reactions (ADRs). The fully documented safety analysis set comprised 796 patients, only 9.2% of whom terminated the study for reasons related to AEs. A total of 867 AEs were recorded, and 596 of these were classified as ADRs; the most common were throat irritation (19.1%), oral paresthesia (8.2%), oral pruritus (6.5%) and oedema mouth 213 (6.2%). Importantly, 78.2% of the ADRs were mild or moderate, and no adrenaline use was recorded. In conclusion, Eberle et al.'s detailed post‐marketing study has provided the first ‘real‐life’ confirmation of the good safety profile observed during clinical development of the 300 IR 5‐grass pollen sublingual tablet. Peter Eberle Preventive sublingual immunotherapy in preschool children: first evidence for safety and pro‐tolerogenic effects How can the spread of new sensitizations at a young age and the development of allergies thereafter be stopped? Large birth cohort studies have revealed how a clinically healthy newborn becomes sensitized initially to one and later to many allergens before possibly ending up clinically allergic. Different interventional approaches aim to interrupt this development in an early phase. As one approach, allergen‐specific immunotherapy, as used in allergic children, could withhold an IgE‐sensitization from spreading. In this study, Szépfalusi et al. focused on an earlier age period, before children would have developed a defined allergic disease. Children, 2–5 years old (n = 31), were sensitized to either grass pollen or house dust mites but did not show allergen‐specific symptoms. They received sublingually an allergen‐specific immunotherapy extract (n = 15) or placebo (n = 16) according to their sensitization profile and were treated for 2 years. The primary outcome parameter was a reduction of new sensitizations by sublingual immunotherapy. The authors could neither see a decrease nor an increase of IgE‐sensitization in the verum‐treated group as compared to placebo (as measured by Skin Prick Test, IgE ImmunoCAP, IgE micro array). The authors also assessed immunological parameters, and here, most strikingly, they could observe a significant increase of allergen‐specific IgG to house dust mite (p < 0.05). More specifically, an IL10‐dependent inhibition of allergen‐specific T cell proliferation (p < 0.05) was observed in the treatment group but not in the placebo group. Although this study is of pilot character (n = 31) and thus cannot reveal whether IgE‐sensitization‐spreading can effectively be modified by early (secondary preventive) allergen‐specific immunotherapy, it nevertheless supports that the application mode (sublingual) can effectively and safely be applied to small children of age 2–4 years and most importantly leads to a remarkable pro‐tolerogenic immune‐modulation. Thus, this approach of preventive SLIT deserves more focus in larger trials with adapted allergen sources. Zsolt Szépfalusi$

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