No abstract

While both the incidence and general awareness of food allergies is increasing, the variety and clinical availability of therapeutics remain limited. Therefore, investigations into the potential factors contributing to the development of food allergy (FA) and the mechanisms of natural tolerance or induced desensitization are required. In addition, a detailed understanding of the pathophysiology of food allergies is needed to generate compelling, enduring, and safe treatment options. New findings regarding the contribution of barrier function, the effect of emollient interventions, mechanisms of allergen recognition, and the contributions of specific immune cell subsets through rodent models and human clinical studies provide novel insights. With the first approved treatment for peanut allergy, the clinical management of FA is evolving toward less intensive, alternative approaches involving fixed doses, lower maintenance dose targets, coadministration of biologicals, adjuvants, and tolerance‐inducing formulations. The ultimate goal is to improve immunotherapy and develop precision‐based medicine via risk phenotyping allowing optimal treatment for each food‐allergic patient.

The use of antibiotics as well as changes in the gut microbiota have been linked to development of food allergy in childhood. It remains unknown whether administration of a single clinically relevant antibiotic directly promotes food allergy development when administrated during the sensitisation phase in an experimental animal model. We investigated whether the antibiotic amoxicillin affected gut microbiota composition, development of cow's milk allergy (CMA) and frequencies of allergic effector cells and regulatory T cells in the intestine. Brown Norway rats were given daily oral gavages of amoxicillin for six weeks and whey protein concentrate (WPC) with or without cholera toxin three times per week for the last five weeks. Microbiota composition in faeces and small intestine was analysed by 16S rRNA sequencing. The development of CMA was assessed by WPC‐specific IgE in serum, ear swelling response to WPC and body hypothermia following oral gavage of WPC. Allergic effector cells were analysed by histology, and frequencies of regulatory and activated T cells were analysed by flow cytometry. Amoxicillin administration reduced faecal microbiota diversity, reduced the relative abundance of Firmicutes and increased the abundance of Bacteroidetes and Proteobacteria. Despite these effects, amoxicillin did not affect the development of CMA, nor the frequencies of allergic effector cells or regulatory T cells. Thus, amoxicillin does not carry a direct risk for food allergy development when administrated in an experimental model of allergic sensitisation to WPC via the gut. This finding suggests that confounding factors may better explain the epidemiological link between antibiotic use and food allergy.

While both the incidence and general awareness of food allergies is increasing, the variety and clinical availability of therapeutics remain limited. Therefore, investigations into the potential factors contributing to the development of food allergy and the mechanisms of natural tolerance or induced desensitization are required. In addition, a detailed understanding of the pathophysiology of food allergies is needed to generate compelling, enduring, and safe treatment options. New findings regarding the contribution of barrier function, the effect of emollient interventions, mechanisms of allergen recognition, and the contributions of specific immune cell subsets through rodent models and human clinical studies provide novel insights. With the first approved treatment for peanut allergy, the clinical management of food allergy is evolving towards less intensive, alternative approaches involving fixed doses, lower maintenance dose targets, co-administration of biologicals, adjuvants, and tolerance-inducing formulations. The ultimate goal is to improve immunotherapy and develop precision-based medicine via risk phenotyping allowing optimal treatment for each food-allergic patient.

Soft tissue sarcomas in neonates are rare and heterogeneous tumors. We report an aggressive neonatal undifferentiated round cell sarcoma with a YWHAE:NUTM2B fusion. The tumor was identified antenatally and the neonate underwent surgical resection at four days of age. Whole-genome and transcriptome sequencing of tumour and germline was undertaken to provide molecular characterization and elucidate possible novel therapies. In addition to molecular characterization of a YWHAE:NUTM2B fusion, RNA expression outliers were described. Targeted therapy was not pursued due to rapid clinical decline. Understanding the genomic profile of rare tumors remains important in the development of novel therapeutic strategies.