RT Journal Article
T1 Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome
A1 Camino Mera, Alba
A1 Pardo Seco, Jacobo José
A1 Bello, Xabier
A1 Martinón Torres, Federico
A1 Gómez Carballa, Alberto
A1 Salas Ellacuriaga, Antonio
K1 ATG16L1
K1 DGKZ
K1 Exomes
K1 Food allergy
K1 FPIES
K1 NGS
K1 RBM8A
AB BackgroundFood 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.MethodsBlood samples from 41 patients with oral food challenge-proven FPIES were collected for a comprehensive whole exome sequencing association study.ResultsNotable 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).ConclusionsThis 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.
PB Wiley
YR 2024
FD 2024-09-30
LK https://hdl.handle.net/10347/38111
UL https://hdl.handle.net/10347/38111
LA eng
NO Camino-Mera, A., Pardo-Seco, J., Bello, X., Argiz, L., Boyle, R., Custovic, A., Herberg, J., Kaforou, M., Arasi, S., Fiocchi, A., Pecora, V., Barni, S., Mori, F., Bracamonte, T., Echeverria, L., O'Valle-Aísa, V., Hernández-Martínez, N., Carballeira, I., García, E., Garcia-Magan, C., Moure-González, J., Gonzalez-Delgado, P., Garriga-Baraut, T., Infante, S., Zambrano-Ibarra, G., Tomás-Pérez, M., Machinena, A., Pascal, M., Prieto, A., Vázquez-Cortes, S., Fernández-Rivas, M., Vila, L., Alsina, L., Torres, M., Mangone, G., Quirce, S., Martinón-Torres, F., Vázquez-Ortiz, M., Gómez-Carballa, A. and Salas, A. (2024), Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome. Clin Exp Allergy, 54: 919-929. https://doi.org/10.1111/cea.14564
NO This study was supported by European Union's Horizon 2020 research and innovation programme (668303) and Strategic Health Action, ‘Instituto de Salud Carlos III’ (TRINEO: PI22/00162, DIAVIR: DTS19/00049, Resvi-Omics: PI19/01039, ReSVinext: PI16/01569, Enterogen: PI19/01090, OMI-COVI-VAC: PI22/00406, BIO-FPIES: PI19/00497, IN607B 2020/08, IN607A 2023/02, GEN-COVID IN845D 2020/23, IIN607A2021/05, PID2022-142156OB-I00, CB21/06/00103, CP23/00080).
DS Minerva
RD 28 abr 2026