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Multiomics integration of 22 immune-mediated monogenic diseases reveals an emergent axis of human immune health.
Sparks, Rachel; Rachmaninoff, Nicholas; Hirsch, Dylan C; Bansal, Neha; Lau, William W; Martins, Andrew J; Chen, Jinguo; Liu, Candace C; Cheung, Foo; Failla, Laura E; Biancotto, Angelique; Fantoni, Giovanna; Sellers, Brian A; Chawla, Daniel G; Howe, Katherine N; Mostaghimi, Darius; Farmer, Rohit; Kotliarov, Yuri; Calvo, Katherine R; Palmer, Cindy; Daub, Janine; Foruraghi, Ladan; Kreuzburg, Samantha; Treat, Jennifer; Urban, Amanda K; Jones, Anne; Romeo, Tina; Deuitch, Natalie T; Moura, Natalia Sampaio; Weinstein, Barbara; Moir, Susan; Ferrucci, Luigi; Barron, Karyl S; Aksentijevich, Ivona; Kleinstein, Steven H; Townsley, Danielle M; Young, Neal S; Frischmeyer-Guerrerio, Pamela A; Uzel, Gulbu; Pinto-Patarroyo, Gineth Paola; Cudrici, Cornelia D; Hoffmann, Patrycja; Stone, Deborah L; Ombrello, Amanda K; Freeman, Alexandra F; Zerbe, Christa S; Kastner, Daniel L; Holland, Steven M; Tsang, John S.
Afiliación
  • Sparks R; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Rachmaninoff N; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Hirsch DC; Graduate Program in Biological Sciences, University of Maryland, College Park, MD 20742, USA.
  • Bansal N; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Lau WW; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Martins AJ; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Chen J; Office of Intramural Research, CIT, NIH, Bethesda, MD 20892, USA.
  • Liu CC; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Cheung F; NIH Center for Human Immunology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Failla LE; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Biancotto A; NIH Center for Human Immunology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Fantoni G; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Sellers BA; NIH Center for Human Immunology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Chawla DG; NIH Center for Human Immunology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Howe KN; NIH Center for Human Immunology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Mostaghimi D; Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.
  • Farmer R; Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Kotliarov Y; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Calvo KR; NIH Center for Human Immunology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Palmer C; NIH Center for Human Immunology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Daub J; Hematology Section, Department of Laboratory Medicine, NIH Clinical Center, Bethesda, MD 20892, USA.
  • Foruraghi L; Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Kreuzburg S; Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Treat J; Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Urban AK; Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Jones A; Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Romeo T; Clinical Research Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21701, USA.
  • Deuitch NT; Inflammatory Diseases Section, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Moura NS; Inflammatory Diseases Section, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Weinstein B; Inflammatory Diseases Section, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Moir S; Inflammatory Diseases Section, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Ferrucci L; Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.
  • Barron KS; Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD 20892, USA.
  • Aksentijevich I; Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA.
  • Kleinstein SH; Divison of Intramural Research, NIAID, NIH, Bethesda, MD 20892, USA.
  • Townsley DM; Inflammatory Diseases Section, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Young NS; Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.
  • Frischmeyer-Guerrerio PA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Uzel G; Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Pinto-Patarroyo GP; Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.
  • Cudrici CD; Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.
  • Hoffmann P; Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
  • Stone DL; Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
  • Ombrello AK; Inflammatory Diseases Section, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Freeman AF; National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda MD 20892, USA.
  • Zerbe CS; Inflammatory Diseases Section, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Kastner DL; Inflammatory Diseases Section, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Holland SM; Inflammatory Diseases Section, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Tsang JS; Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
Res Sq ; 2023 Mar 20.
Article en En | MEDLINE | ID: mdl-36993430
ABSTRACT
Monogenic diseases are often studied in isolation due to their rarity. Here we utilize multiomics to assess 22 monogenic immune-mediated conditions with age- and sex-matched healthy controls. Despite clearly detectable disease-specific and "pan-disease" signatures, individuals possess stable personal immune states over time. Temporally stable differences among subjects tend to dominate over differences attributable to disease conditions or medication use. Unsupervised principal variation analysis of personal immune states and machine learning classification distinguishing between healthy controls and patients converge to a metric of immune health (IHM). The IHM discriminates healthy from multiple polygenic autoimmune and inflammatory disease states in independent cohorts, marks healthy aging, and is a pre-vaccination predictor of antibody responses to influenza vaccination in the elderly. We identified easy-to-measure circulating protein biomarker surrogates of the IHM that capture immune health variations beyond age. Our work provides a conceptual framework and biomarkers for defining and measuring human immune health.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos