Alba Camino-Mera, Jacobo Pardo-Seco, Xabier Bello, Laura Argiz, Robert J Boyle, Adnan Custovic, Jethro Herberg, Myrsini Kaforou, Stefania Arasi, Alessandro Fiocchi, Valentina Pecora, Simona Barni, Francesca Mori, Teresa Bracamonte, Luis Echeverria, Virginia O'Valle-Aísa, Noelia Lara Hernández-Martínez, Iria Carballeira, Emilio García, Carlos Garcia-Magan, José Domingo Moure-González, Purificación Gonzalez-Delgado, Teresa Garriga-Baraut, Sonsoles Infante, Gabriela Zambrano-Ibarra, Margarita Tomás-Pérez, Adrianna Machinena, Mariona Pascal, Ana Prieto, Sonia Vázquez-Cortes, Montserrat Fernández-Rivas, Leticia Vila, Laia Alsina, María José Torres, Giusi Mangone, Santiago Quirce, Federico Martinón-Torres, Marta Vázquez-Ortiz, Alberto Gómez-Carballa, Antonio Salas
{"title":"全外显子组测序发现食物蛋白诱发小肠结肠炎综合征的上皮和免疫功能障碍相关生物标记物","authors":"Alba Camino-Mera, Jacobo Pardo-Seco, Xabier Bello, Laura Argiz, Robert J Boyle, Adnan Custovic, Jethro Herberg, Myrsini Kaforou, Stefania Arasi, Alessandro Fiocchi, Valentina Pecora, Simona Barni, Francesca Mori, Teresa Bracamonte, Luis Echeverria, Virginia O'Valle-Aísa, Noelia Lara Hernández-Martínez, Iria Carballeira, Emilio García, Carlos Garcia-Magan, José Domingo Moure-González, Purificación Gonzalez-Delgado, Teresa Garriga-Baraut, Sonsoles Infante, Gabriela Zambrano-Ibarra, Margarita Tomás-Pérez, Adrianna Machinena, Mariona Pascal, Ana Prieto, Sonia Vázquez-Cortes, Montserrat Fernández-Rivas, Leticia Vila, Laia Alsina, María José Torres, Giusi Mangone, Santiago Quirce, Federico Martinón-Torres, Marta Vázquez-Ortiz, Alberto Gómez-Carballa, Antonio Salas","doi":"10.1111/cea.14564","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Blood samples from 41 patients with oral food challenge-proven FPIES were collected for a comprehensive whole exome sequencing association study.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":null,"pages":null},"PeriodicalIF":6.3000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome.\",\"authors\":\"Alba Camino-Mera, Jacobo Pardo-Seco, Xabier Bello, Laura Argiz, Robert J Boyle, Adnan Custovic, Jethro Herberg, Myrsini Kaforou, Stefania Arasi, Alessandro Fiocchi, Valentina Pecora, Simona Barni, Francesca Mori, Teresa Bracamonte, Luis Echeverria, Virginia O'Valle-Aísa, Noelia Lara Hernández-Martínez, Iria Carballeira, Emilio García, Carlos Garcia-Magan, José Domingo Moure-González, Purificación Gonzalez-Delgado, Teresa Garriga-Baraut, Sonsoles Infante, Gabriela Zambrano-Ibarra, Margarita Tomás-Pérez, Adrianna Machinena, Mariona Pascal, Ana Prieto, Sonia Vázquez-Cortes, Montserrat Fernández-Rivas, Leticia Vila, Laia Alsina, María José Torres, Giusi Mangone, Santiago Quirce, Federico Martinón-Torres, Marta Vázquez-Ortiz, Alberto Gómez-Carballa, Antonio Salas\",\"doi\":\"10.1111/cea.14564\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Blood samples from 41 patients with oral food challenge-proven FPIES were collected for a comprehensive whole exome sequencing association study.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":10207,\"journal\":{\"name\":\"Clinical and Experimental Allergy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.3000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Experimental Allergy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/cea.14564\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Allergy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cea.14564","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
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-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.
期刊介绍:
Clinical & Experimental Allergy strikes an excellent balance between clinical and scientific articles and carries regular reviews and editorials written by leading authorities in their field.
In response to the increasing number of quality submissions, since 1996 the journals size has increased by over 30%. Clinical & Experimental Allergy is essential reading for allergy practitioners and research scientists with an interest in allergic diseases and mechanisms. Truly international in appeal, Clinical & Experimental Allergy publishes clinical and experimental observations in disease in all fields of medicine in which allergic hypersensitivity plays a part.