Scientific publications
Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome. Scientific Publication
Alba Camino-Mera 1 2 3 , Jacobo Pardo-Seco 1 2 3 , Xabier Bello 1 2 3 , Laura Argiz 4 , Robert J Boyle 5 , Adnan Custovic 5 , Jethro Herberg 6 , Myrsini Kaforou 6 , Stefania Arasi 7 , Alessandro Fiocchi 7 , Valentina Pecora 7 , Simona Barni 8 , Francesca Mori 8 , Teresa Bracamonte 9 , Luis Echeverria 9 , Virginia O'Valle-Aísa 10 , Noelia Lara Hernández-Martínez 10 , Iria Carballeira 11 , Emilio García 11 , Carlos Garcia-Magan 12 , José Domingo Moure-González 12 , Purificación Gonzalez-Delgado 13 , Teresa Garriga-Baraut 14 , Sonsoles Infante 15 , Gabriela Zambrano-Ibarra 15 , Margarita Tomás-Pérez 15 , Adrianna Machinena 16 , Mariona Pascal 17 18 , Ana Prieto 19 , Sonia Vázquez-Cortes 20 , Montserrat Fernández-Rivas 21 , Leticia Vila 22 , Laia Alsina 23 , María José Torres 24 25 26 27 , Giusi Mangone 28 , Santiago Quirce 29 , Federico Martinón-Torres 1 3 30 , Marta Vázquez-Ortiz 5 , Alberto Gómez-Carballa 1 2 3 , Antonio Salas 1 2 3
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-β 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.
CITATION Clin Exp Allergy. 2024 Sep 30. doi: 10.1111/cea.14564
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