Yamini V Virkud, Jennifer N Styles, Rachel S Kelly, Sarita U Patil, Bert Ruiter, Neal P Smith, Clary Clish, Craig E Wheelock, Juan C Celedón, Augusto A Litonjua, Supinda Bunyavanich, Scott T Weiss, Erin S Baker, Jessica A Lasky-Su, Wayne G Shreffler
{"title":"基于代谢组学分析的 IgE 介导的食物过敏中的免疫调节代谢物和口服免疫疗法的结果。","authors":"Yamini V Virkud, Jennifer N Styles, Rachel S Kelly, Sarita U Patil, Bert Ruiter, Neal P Smith, Clary Clish, Craig E Wheelock, Juan C Celedón, Augusto A Litonjua, Supinda Bunyavanich, Scott T Weiss, Erin S Baker, Jessica A Lasky-Su, Wayne G Shreffler","doi":"10.1111/pai.14267","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.</p><p><strong>Objective: </strong>To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT.</p><p><strong>Methods: </strong>Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes.</p><p><strong>Results: </strong>Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10<sup>-20</sup>) and linoleic acid derivatives (q = 3.8 × 10<sup>-5</sup>) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10<sup>-8</sup>), eicosanoids (q = 7.9 × 10<sup>-7</sup>), and histidine pathways (q = .015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p = .0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p = .01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p = .0015) were higher in SU.</p><p><strong>Conclusions: </strong>We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.</p>","PeriodicalId":19929,"journal":{"name":"Pediatric Allergy and Immunology","volume":"35 11","pages":"e14267"},"PeriodicalIF":4.3000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756372/pdf/","citationCount":"0","resultStr":"{\"title\":\"Immunomodulatory metabolites in IgE-mediated food allergy and oral immunotherapy outcomes based on metabolomic profiling.\",\"authors\":\"Yamini V Virkud, Jennifer N Styles, Rachel S Kelly, Sarita U Patil, Bert Ruiter, Neal P Smith, Clary Clish, Craig E Wheelock, Juan C Celedón, Augusto A Litonjua, Supinda Bunyavanich, Scott T Weiss, Erin S Baker, Jessica A Lasky-Su, Wayne G Shreffler\",\"doi\":\"10.1111/pai.14267\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.</p><p><strong>Objective: </strong>To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT.</p><p><strong>Methods: </strong>Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes.</p><p><strong>Results: </strong>Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10<sup>-20</sup>) and linoleic acid derivatives (q = 3.8 × 10<sup>-5</sup>) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10<sup>-8</sup>), eicosanoids (q = 7.9 × 10<sup>-7</sup>), and histidine pathways (q = .015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p = .0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p = .01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p = .0015) were higher in SU.</p><p><strong>Conclusions: </strong>We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.</p>\",\"PeriodicalId\":19929,\"journal\":{\"name\":\"Pediatric Allergy and Immunology\",\"volume\":\"35 11\",\"pages\":\"e14267\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756372/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Allergy and Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/pai.14267\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Allergy and Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/pai.14267","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ALLERGY","Score":null,"Total":0}
Immunomodulatory metabolites in IgE-mediated food allergy and oral immunotherapy outcomes based on metabolomic profiling.
Background: The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.
Objective: To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT.
Methods: Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes.
Results: Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10-20) and linoleic acid derivatives (q = 3.8 × 10-5) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10-8), eicosanoids (q = 7.9 × 10-7), and histidine pathways (q = .015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p = .0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p = .01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p = .0015) were higher in SU.
Conclusions: We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.
期刊介绍：
Pediatric Allergy and Immunology is the world''s leading journal in pediatric allergy, publishing original contributions and comprehensive reviews related to the understanding and treatment of immune deficiency and allergic inflammatory and infectious diseases in children.
Other areas of interest include: development of specific and accessory immunity; the immunological interaction during pregnancy and lactation between mother and child.
As Pediatric Allergy and Immunology promotes communication between scientists engaged in basic research and clinicians working with children, we publish both clinical and experimental work.
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