Rachel Sparks, Nicholas Rachmaninoff, William W. Lau, Dylan C. Hirsch, Neha Bansal, Andrew J. Martins, Jinguo Chen, Candace C. Liu, Foo Cheung, Laura E. Failla, Angelique Biancotto, Giovanna Fantoni, Brian A. Sellers, Daniel G. Chawla, Katherine N. Howe, Darius Mostaghimi, Rohit Farmer, Yuri Kotliarov, Katherine R. Calvo, Cindy Palmer, Janine Daub, Ladan Foruraghi, Samantha Kreuzburg, Jennifer D. Treat, Amanda K. Urban, Anne Jones, Tina Romeo, Natalie T. Deuitch, Natalia Sampaio Moura, Barbara Weinstein, Susan Moir, Luigi Ferrucci, Karyl S. Barron, Ivona Aksentijevich, Steven H. Kleinstein, Danielle M. Townsley, Neal S. Young, Pamela A. Frischmeyer-Guerrerio, Gulbu Uzel, Gineth Paola Pinto-Patarroyo, Cornelia D. Cudrici, Patrycja Hoffmann, Deborah L. Stone, Amanda K. Ombrello, Alexandra F. Freeman, Christa S. Zerbe, Daniel L. Kastner, Steven M. Holland, John S. Tsang
{"title":"A unified metric of human immune health","authors":"Rachel Sparks, Nicholas Rachmaninoff, William W. Lau, Dylan C. Hirsch, Neha Bansal, Andrew J. Martins, Jinguo Chen, Candace C. Liu, Foo Cheung, Laura E. Failla, Angelique Biancotto, Giovanna Fantoni, Brian A. Sellers, Daniel G. Chawla, Katherine N. Howe, Darius Mostaghimi, Rohit Farmer, Yuri Kotliarov, Katherine R. Calvo, Cindy Palmer, Janine Daub, Ladan Foruraghi, Samantha Kreuzburg, Jennifer D. Treat, Amanda K. Urban, Anne Jones, Tina Romeo, Natalie T. Deuitch, Natalia Sampaio Moura, Barbara Weinstein, Susan Moir, Luigi Ferrucci, Karyl S. Barron, Ivona Aksentijevich, Steven H. Kleinstein, Danielle M. Townsley, Neal S. Young, Pamela A. Frischmeyer-Guerrerio, Gulbu Uzel, Gineth Paola Pinto-Patarroyo, Cornelia D. Cudrici, Patrycja Hoffmann, Deborah L. Stone, Amanda K. Ombrello, Alexandra F. Freeman, Christa S. Zerbe, Daniel L. Kastner, Steven M. Holland, John S. Tsang","doi":"10.1038/s41591-024-03092-6","DOIUrl":null,"url":null,"abstract":"<p>Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls. Despite the high penetrance of monogenic lesions, differences between individuals in diverse immune parameters tended to dominate over those attributable to disease conditions or medication use. Unsupervised or supervised machine learning independently identified a score that distinguished healthy participants from patients with monogenic diseases, thus suggesting a quantitative immune health metric (IHM). In ten independent datasets, the IHM discriminated healthy from polygenic autoimmune and inflammatory disease states, marked aging in clinically healthy individuals, tracked disease activities and treatment responses in both immunological and nonimmunological diseases, and predicted age-dependent antibody responses to immunizations with different vaccines. This discriminatory power goes beyond that of the classical inflammatory biomarkers C-reactive protein and interleukin-6. Thus, deviations from health in diverse conditions, including aging, have shared systemic immune consequences, and we provide a web platform for calculating the IHM for other datasets, which could empower precision medicine.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":58.7000,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41591-024-03092-6","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls. Despite the high penetrance of monogenic lesions, differences between individuals in diverse immune parameters tended to dominate over those attributable to disease conditions or medication use. Unsupervised or supervised machine learning independently identified a score that distinguished healthy participants from patients with monogenic diseases, thus suggesting a quantitative immune health metric (IHM). In ten independent datasets, the IHM discriminated healthy from polygenic autoimmune and inflammatory disease states, marked aging in clinically healthy individuals, tracked disease activities and treatment responses in both immunological and nonimmunological diseases, and predicted age-dependent antibody responses to immunizations with different vaccines. This discriminatory power goes beyond that of the classical inflammatory biomarkers C-reactive protein and interleukin-6. Thus, deviations from health in diverse conditions, including aging, have shared systemic immune consequences, and we provide a web platform for calculating the IHM for other datasets, which could empower precision medicine.
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