PMID- 30107053 OWN - NLM STAT- MEDLINE DCOM- 20191114 LR - 20230804 IS - 1365-2222 (Electronic) IS - 0954-7894 (Print) IS - 0954-7894 (Linking) VI - 48 IP - 12 DP - 2018 Dec TI - Novel eosinophilic gene expression networks associated with IgE in two distinct asthma populations. PG - 1654-1664 LID - 10.1111/cea.13249 [doi] AB - BACKGROUND: Asthma represents a significant public health burden; however, novel biological therapies targeting immunoglobulin E (IgE)-mediated pathways have widened clinical treatment options for the disease. OBJECTIVE: In this study, we sought to identify gene transcripts and gene networks involved in the determination of serum IgE levels in people with asthma that can help inform the development of novel therapeutic agents. METHODS: We analysed gene expression data from a cross-sectional study of 326 Costa Rican children with asthma, aged 6 to 12 years, from the Genetics of Asthma in Costa Rica Study and 610 young adults with asthma, aged 16 to 25 years, from the Childhood Asthma Management Program trial. We utilized differential gene expression analysis and performed weighted gene coexpression network analysis on 25 060 genes, to identify gene transcripts and network modules associated with total IgE, adjusting for age and gender. We used pathway enrichment analyses to identify key biological pathways underlying significant modules. We compared findings that replicated between both populations. RESULTS: We identified 31 transcripts associated with total IgE that replicated between the two study cohorts. These results were notable for increased eosinophil-related transcripts (including IL5RA, CLC, SMPD3, CCL23 and CEBPE). Pathway enrichment identified the regulation of T cell tolerance as important in the determination of total IgE levels, supporting a key role for IDO1. CONCLUSIONS AND CLINICAL RELEVANCE: These results provide robust evidence that biologically meaningful gene expression profiles (relating to eosinophilic and regulatory T cell pathways in particular) associated with total IgE levels can be identified in individuals diagnosed with asthma during childhood. These profiles and their constituent genes may represent novel therapeutic targets. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Virkud, Yamini V AU - Virkud YV AUID- ORCID: 0000-0001-7328-7215 AD - Division of Allergy and Immunology, Department of Pediatrics, Harvard Medical School, Massachusetts General Hospital for Children, Boston, Massachusetts. AD - Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Kelly, Rachel S AU - Kelly RS AUID- ORCID: 0000-0003-3023-1822 AD - Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Croteau-Chonka, Damien C AU - Croteau-Chonka DC AD - Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Celedon, Juan C AU - Celedon JC AUID- ORCID: 0000-0002-6139-5320 AD - Division of Pediatric Pulmonary Medicine, Allergy and Immunology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania. FAU - Dahlin, Amber AU - Dahlin A AD - Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Avila, Lydiana AU - Avila L AD - Department of Pediatrics, Hospital Nacional de Ninos, San Jose, Costa Rica. FAU - Raby, Benjamin A AU - Raby BA AD - Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Weiss, Scott T AU - Weiss ST AD - Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Lasky-Su, Jessica A AU - Lasky-Su JA AD - Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts. LA - eng GR - R01 HL123915/HL/NHLBI NIH HHS/United States GR - R01 HL141826/HL/NHLBI NIH HHS/United States GR - K01 HL127265/HL/NHLBI NIH HHS/United States GR - P01 HL132825/HL/NHLBI NIH HHS/United States GR - K23 AI130408/AI/NIAID NIH HHS/United States GR - R37 HL066289/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20181121 PL - England TA - Clin Exp Allergy JT - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JID - 8906443 RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Asthma/epidemiology/*genetics/*immunology MH - Child MH - Computational Biology/methods MH - Costa Rica/epidemiology MH - Eosinophilia/genetics/immunology MH - Eosinophils/*immunology/*metabolism MH - Female MH - *Gene Expression MH - Gene Expression Profiling MH - Gene Expression Regulation MH - Gene Ontology MH - *Gene Regulatory Networks MH - Humans MH - Immunoglobulin E/*immunology MH - Male PMC - PMC6659730 MID - NIHMS1014793 OTO - NOTNLM OT - allergic asthma OT - computational biology OT - eosinophils OT - gene expression OT - network medicine COIS- Conflict of Interest: None of the authors involved in this manuscript have any conflicts of interest relevant to this work EDAT- 2018/08/15 06:00 MHDA- 2019/11/15 06:00 PMCR- 2019/12/01 CRDT- 2018/08/15 06:00 PHST- 2017/04/27 00:00 [received] PHST- 2018/07/02 00:00 [revised] PHST- 2018/07/02 00:00 [accepted] PHST- 2018/08/15 06:00 [pubmed] PHST- 2019/11/15 06:00 [medline] PHST- 2018/08/15 06:00 [entrez] PHST- 2019/12/01 00:00 [pmc-release] AID - 10.1111/cea.13249 [doi] PST - ppublish SO - Clin Exp Allergy. 2018 Dec;48(12):1654-1664. doi: 10.1111/cea.13249. Epub 2018 Nov 21.