Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a food allergy primarily affecting infants, often leading to vomiting and shock. Due to its poorly understood pathophysiology and lack of specific biomarkers, diagnosis is frequently delayed. Understanding FPIES genetics can shed light on disease susceptibility and pathophysiology-key to developing diagnostic, prognostic, preventive and therapeutic strategies. Using a well-characterised cohort of patients we explored the potential genome-wide susceptibility factors underlying FPIES. METHODS: Blood samples from 41 patients with oral food challenge-proven FPIES were collected for a comprehensive whole exome sequencing association study. RESULTS: Notable genetic variants, including rs872786 (RBM8A), rs2241880 (ATG16L1) and rs2289477 (ATG16L1), were identified as significant findings in FPIES. A weighted SKAT model identified six other associated genes including DGKZ and SIRPA. DGKZ induces TGF-ß signalling, crucial for epithelial barrier integrity and IgA production; RBM8A is associated with thrombocytopenia absent radius syndrome, frequently associated with cow's milk allergy; SIRPA is associated with increased neutrophils/monocytes in inflamed tissues as often observed in FPIES; ATG16L1 is associated with inflammatory bowel disease. Coexpression correlation analysis revealed a functional correlation between RBM8A and filaggrin gene (FLG) in stomach and intestine tissue, with filaggrin being a known key pathogenic and risk factor for IgE-mediated food allergy. A transcriptome-wide association study suggested genetic variability in patients impacted gene expression of RBM8A (stomach and pancreas) and ATG16L1 (transverse colon). CONCLUSIONS: This study represents the first case-control exome association study of FPIES patients and marks a crucial step towards unravelling genetic susceptibility factors underpinning the syndrome. Our findings highlight potential factors and pathways contributing to FPIES, including epithelial barrier dysfunction and immune dysregulation. While these results are novel, they are preliminary and need further validation in a second cohort of patients.

Sublingual allergen immunotherapy for respiratory allergy: a systematic review.

The objective of the systematic review is to provide complete and updated information on efficacy and safety of sublingual immunotherapy (SLIT) formulations for the treatment of allergic respiratory diseases (ARDs). The literature search was conducted on PubMed database, involving double-blind, randomized clinical trials published between January 1992 and 2018, written in English, and performed in humans. The number of articles finally selected for review was 112. Data from the majority of properly controlled clinical trials demonstrate that SLIT is effective not only with short-term use (first year) but also with long-term use (up to the third year of active therapy), for treating ARDs in children and adults. Both continuous and discontinuous schemes of administration showed significant reductions in symptom and medication scores. Moreover, a SLIT-induced disease-modifying effect has been documented mainly with grass pollen extracts, since improvement is maintained during at least 2 years of follow-up after a 3-year treatment period. Additionally, allergen immunotherapy should also be considered a preventive strategy, especially for decreasing bronchial asthma incidence in children and adolescents with allergic rhinitis treated with SLIT. This therapy is also safe, producing only a few mainly local and mild-to-moderate adverse events, and usually self-limited in time. The registration and authorization of allergen SLIT preparations (grasses and house-dust mite tablets) as drugs by regulatory agencies, such as the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA), has represented a landmark in allergy immunotherapy research. Further long-term studies, specially designed with allergens other than grass pollen or house-dust mites, not only in allergic rhinoconjunctivitis but also on asthmatic subjects, as well as studies comparing different administration schedules and/or routes, are required in order to continue the progress in the modern development of this particularly promising therapy.