Publications by authors named "Elana Shaw"

4 Publications

  • Page 1 of 1

The Influence of Immune Immaturity on Outcome After Virus Infections.

J Allergy Clin Immunol Pract 2021 02;9(2):641-650

Human Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address:

Maturation of the adaptive immune response is typically thought to improve outcome to virus infections. However, long-standing observations of natural infections with old viruses such as Epstein-Barr virus and newer observations of emerging viruses such as severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 suggest that immune immaturity may be beneficial for outcome. Mechanistic studies and studies of patients with inborn errors of immunity have revealed that immune dysregulation reflecting inappropriate antibody and T-cell responses plays a crucial role in causing bystander inflammation and more severe disease. Further evidence supports a role for innate immunity in normally regulating adaptive immune responses. Thus, changes in immune responses that normally occur with age may help explain an apparent protective role of immune immaturity during virus infections.
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http://dx.doi.org/10.1016/j.jaip.2020.11.016DOI Listing
February 2021

Virulence attenuating combination therapy: a potential multi-target synergy approach to treat infections in cystic fibrosis patients.

RSC Med Chem 2020 Mar 19;11(3):358-369. Epub 2020 Feb 19.

Department of Chemistry , Emory University , 1515 Dickey Drive , Atlanta , Georgia 30322 , USA . Email:

The World Health Organization considers the discovery of new treatments for a top priority. Virulence attenuating combination therapy (VACT) is a pragmatic strategy to improve bacterial clearance, repurpose outmoded antibiotics, improve drug efficacy at lower doses, and reduce the evolution of resistance. and studies have shown that adding a quorum sensing inhibitor or an extracellular polymeric substance repressor to classical antibiotics synergistically improves antipseudomonal activity. This review highlights why VACT could specifically benefit cystic fibrosis patients harboring chronic infections, outlines the current landscape of synergistic combinations between virulence-targeting small-molecules and anti-pseudomonal drugs, and suggests future directions for VACT research.
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http://dx.doi.org/10.1039/c9md00566hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580779PMC
March 2020

An immune-based biomarker signature is associated with mortality in COVID-19 patients.

JCI Insight 2021 01 11;6(1). Epub 2021 Jan 11.

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.

Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN-, type II IFN-, and NF-κB-dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients' first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.
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http://dx.doi.org/10.1172/jci.insight.144455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821609PMC
January 2021

Autoantibodies against type I IFNs in patients with life-threatening COVID-19.

Authors:
Paul Bastard Lindsey B Rosen Qian Zhang Eleftherios Michailidis Hans-Heinrich Hoffmann Yu Zhang Karim Dorgham Quentin Philippot Jérémie Rosain Vivien Béziat Jérémy Manry Elana Shaw Liis Haljasmägi Pärt Peterson Lazaro Lorenzo Lucy Bizien Sophie Trouillet-Assant Kerry Dobbs Adriana Almeida de Jesus Alexandre Belot Anne Kallaste Emilie Catherinot Yacine Tandjaoui-Lambiotte Jeremie Le Pen Gaspard Kerner Benedetta Bigio Yoann Seeleuthner Rui Yang Alexandre Bolze András N Spaan Ottavia M Delmonte Michael S Abers Alessandro Aiuti Giorgio Casari Vito Lampasona Lorenzo Piemonti Fabio Ciceri Kaya Bilguvar Richard P Lifton Marc Vasse David M Smadja Mélanie Migaud Jérome Hadjadj Benjamin Terrier Darragh Duffy Lluis Quintana-Murci Diederik van de Beek Lucie Roussel Donald C Vinh Stuart G Tangye Filomeen Haerynck David Dalmau Javier Martinez-Picado Petter Brodin Michel C Nussenzweig Stéphanie Boisson-Dupuis Carlos Rodríguez-Gallego Guillaume Vogt Trine H Mogensen Andrew J Oler Jingwen Gu Peter D Burbelo Jeffrey I Cohen Andrea Biondi Laura Rachele Bettini Mariella D'Angio Paolo Bonfanti Patrick Rossignol Julien Mayaux Frédéric Rieux-Laucat Eystein S Husebye Francesca Fusco Matilde Valeria Ursini Luisa Imberti Alessandra Sottini Simone Paghera Eugenia Quiros-Roldan Camillo Rossi Riccardo Castagnoli Daniela Montagna Amelia Licari Gian Luigi Marseglia Xavier Duval Jade Ghosn John S Tsang Raphaela Goldbach-Mansky Kai Kisand Michail S Lionakis Anne Puel Shen-Ying Zhang Steven M Holland Guy Gorochov Emmanuelle Jouanguy Charles M Rice Aurélie Cobat Luigi D Notarangelo Laurent Abel Helen C Su Jean-Laurent Casanova

Science 2020 10 24;370(6515). Epub 2020 Sep 24.

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
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http://dx.doi.org/10.1126/science.abd4585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857397PMC
October 2020