An immune clock of human pregnancy

Nima Aghaeepour; Edward A Ganio; David Mcilwain; Amy S Tsai; Martha Tingle; Sofie Van Gassen; Dyani K Gaudilliere; Quentin Baca; Leslie McNeil; Robin Okada; Mohammad S Ghaemi; David Furman; Ronald J Wong; Virginia D Winn; Maurice L Druzin; Yaser Y El-Sayed; Cecele Quaintance; Ronald Gibbs; Gary L Darmstadt; Gary M Shaw; David K Stevenson; Robert Tibshirani; Garry P Nolan; David B Lewis; Martin S Angst; Brice Gaudilliere

doi:10.1126/sciimmunol.aan2946

An immune clock of human pregnancy

Sci Immunol. 2017 Sep 1;2(15):eaan2946. doi: 10.1126/sciimmunol.aan2946.

Authors

Nima Aghaeepour¹, Edward A Ganio¹, David Mcilwain², Amy S Tsai¹, Martha Tingle¹, Sofie Van Gassen³, Dyani K Gaudilliere⁴, Quentin Baca¹, Leslie McNeil¹, Robin Okada¹, Mohammad S Ghaemi¹, David Furman^{5

6}, Ronald J Wong⁷, Virginia D Winn⁸, Maurice L Druzin⁸, Yaser Y El-Sayed⁸, Cecele Quaintance⁷, Ronald Gibbs⁸, Gary L Darmstadt⁷, Gary M Shaw⁷, David K Stevenson⁷, Robert Tibshirani⁹, Garry P Nolan², David B Lewis¹⁰, Martin S Angst¹, Brice Gaudilliere¹¹

Affiliations

¹ Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94121, USA.
² Department of Microbiology and Immunology, Stanford University, Stanford, CA 94121, USA.
³ Department of Information Technology, Ghent University, and the Center for Inflammation Research, Ghent, Belgium.
⁴ Department of Surgery, Stanford University School of Medicine, Stanford, CA 94121, USA.
⁵ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁶ Institute for Immunogenetics, Jose de San Martin Clinical Hospital, National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina.
⁷ Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94121, USA.
⁸ Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94121, USA.
⁹ Departments of Biomedical Data Sciences and Statistics, Stanford University, Stanford, CA 94121, USA.
¹⁰ Division of Pediatric Immunology and Allergy, Stanford University School of Medicine, Stanford, CA 94121, USA.
¹¹ Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94121, USA. [email protected].

Abstract

The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. Cell signaling-based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy. Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2-dependent STAT5ab signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies.

Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

Abstract

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