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 ligh...

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Autores: Camino-Mera, A, Pardo-Seco, J, Bello, X, Argiz, L, Boyle, RJ, Custovic, A, Herberg, J, Kaforou, M, Arasi, S, Fiocchi, A, Pecora, V, Barni, S, Mori, F, Bracamonte, T, Echeverria, L, O'Valle-Aisa, V, Hernandez-Martinez, NL, Carballeira, I, Garcia, E, Garcia-Magan, C, Moure-Gonzalez, JD, Gonzalez-Delgado, P, Garriga-Baraut, T, Infante, S, Zambrano-Ibarra, G, Tomas-Perez, M, Machinena, A, Pascal, M, Prieto, A, Vazquez-Cortes, S, Fernandez-Rivas, M, Vila, L, Alsina, L, Torres, MJ, Mangone, G, Quirce, S, Martinon-Torres, F, Vazquez-Ortiz, M, Gomez-Carballa, A, Salas, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p11060
Acceso en línea:https://isabial.portalinvestigacion.com/publicaciones11060
https://onlinelibrary.wiley.com/doi/10.1111/cea.14564
Access Level:acceso abierto
Palabra clave:DGKZ
exomes
food allergy
FPIES
NGS
RBM8A
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spelling Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis SyndromeCamino-Mera, APardo-Seco, JBello, XArgiz, LBoyle, RJCustovic, AHerberg, JKaforou, MArasi, SFiocchi, APecora, VBarni, SMori, FBracamonte, TEcheverria, LO'Valle-Aisa, VHernandez-Martinez, NLCarballeira, IGarcia, EGarcia-Magan, CMoure-Gonzalez, JDGonzalez-Delgado, PGarriga-Baraut, TInfante, SZambrano-Ibarra, GTomas-Perez, MMachinena, APascal, MPrieto, AVazquez-Cortes, SFernandez-Rivas, MVila, LAlsina, LTorres, MJMangone, GQuirce, SMartinon-Torres, FVazquez-Ortiz, MGomez-Carballa, ASalas, ADGKZexomesfood allergyFPIESNGSRBM8ABackground 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-beta 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.WILEY2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://isabial.portalinvestigacion.com/publicaciones11060https://onlinelibrary.wiley.com/doi/10.1111/cea.14564CLINICAL AND EXPERIMENTAL ALLERGYISSN: 09547894ISSNe: 13652222reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p110602026-06-12T10:20:37Z
dc.title.none.fl_str_mv Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome
title Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome
spellingShingle Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome
Camino-Mera, A
DGKZ
exomes
food allergy
FPIES
NGS
RBM8A
title_short Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome
title_full Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome
title_fullStr Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome
title_full_unstemmed Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome
title_sort Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome
dc.creator.none.fl_str_mv Camino-Mera, A
Pardo-Seco, J
Bello, X
Argiz, L
Boyle, RJ
Custovic, A
Herberg, J
Kaforou, M
Arasi, S
Fiocchi, A
Pecora, V
Barni, S
Mori, F
Bracamonte, T
Echeverria, L
O'Valle-Aisa, V
Hernandez-Martinez, NL
Carballeira, I
Garcia, E
Garcia-Magan, C
Moure-Gonzalez, JD
Gonzalez-Delgado, P
Garriga-Baraut, T
Infante, S
Zambrano-Ibarra, G
Tomas-Perez, M
Machinena, A
Pascal, M
Prieto, A
Vazquez-Cortes, S
Fernandez-Rivas, M
Vila, L
Alsina, L
Torres, MJ
Mangone, G
Quirce, S
Martinon-Torres, F
Vazquez-Ortiz, M
Gomez-Carballa, A
Salas, A
author Camino-Mera, A
author_facet Camino-Mera, A
Pardo-Seco, J
Bello, X
Argiz, L
Boyle, RJ
Custovic, A
Herberg, J
Kaforou, M
Arasi, S
Fiocchi, A
Pecora, V
Barni, S
Mori, F
Bracamonte, T
Echeverria, L
O'Valle-Aisa, V
Hernandez-Martinez, NL
Carballeira, I
Garcia, E
Garcia-Magan, C
Moure-Gonzalez, JD
Gonzalez-Delgado, P
Garriga-Baraut, T
Infante, S
Zambrano-Ibarra, G
Tomas-Perez, M
Machinena, A
Pascal, M
Prieto, A
Vazquez-Cortes, S
Fernandez-Rivas, M
Vila, L
Alsina, L
Torres, MJ
Mangone, G
Quirce, S
Martinon-Torres, F
Vazquez-Ortiz, M
Gomez-Carballa, A
Salas, A
author_role author
author2 Pardo-Seco, J
Bello, X
Argiz, L
Boyle, RJ
Custovic, A
Herberg, J
Kaforou, M
Arasi, S
Fiocchi, A
Pecora, V
Barni, S
Mori, F
Bracamonte, T
Echeverria, L
O'Valle-Aisa, V
Hernandez-Martinez, NL
Carballeira, I
Garcia, E
Garcia-Magan, C
Moure-Gonzalez, JD
Gonzalez-Delgado, P
Garriga-Baraut, T
Infante, S
Zambrano-Ibarra, G
Tomas-Perez, M
Machinena, A
Pascal, M
Prieto, A
Vazquez-Cortes, S
Fernandez-Rivas, M
Vila, L
Alsina, L
Torres, MJ
Mangone, G
Quirce, S
Martinon-Torres, F
Vazquez-Ortiz, M
Gomez-Carballa, A
Salas, A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DGKZ
exomes
food allergy
FPIES
NGS
RBM8A
topic DGKZ
exomes
food allergy
FPIES
NGS
RBM8A
description 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-beta 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.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://isabial.portalinvestigacion.com/publicaciones11060
https://onlinelibrary.wiley.com/doi/10.1111/cea.14564
url https://isabial.portalinvestigacion.com/publicaciones11060
https://onlinelibrary.wiley.com/doi/10.1111/cea.14564
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv CLINICAL AND EXPERIMENTAL ALLERGY
ISSN: 09547894
ISSNe: 13652222
reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
instname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
instname_str Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
reponame_str r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
collection r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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