Journal article
Adverse outcomes and an immune suppressed endotype in sepsis patients with reduced interferon-γ ELISpot
JCI insight, Vol.9(2), e175785
01/23/2024
DOI: 10.1172/jci.insight.175785
PMCID: PMC10906237
PMID: 38100268
Abstract
Sepsis remains a major clinical challenge for which successful treatment requires greater precision in identifying patients at increased risk of adverse outcomes requiring different therapeutic approaches. Predicting clinical outcomes and immunological endotyping of septic patients has generally relied on using blood protein or mRNA biomarkers, or static cell phenotyping. Here, we sought to determine whether functional immune responsiveness would yield improved precision.
An ex vivo whole blood enzyme-linked immunosorbent (ELISpot) assay for cellular production of interferon-γ (IFN-γ) was evaluated in 107 septic and 68 non-septic patients from five academic health centers using blood samples collected on days 1, 4 and 7 following ICU admission.
Compared with 46 healthy subjects, unstimulated and stimulated whole blood IFNγ expression were either increased or unchanged, respectively, in septic and nonseptic ICU patients. However, in septic patients who did not survive 180 days, stimulated whole blood IFNγ expression was significantly reduced on ICU days 1, 4 and 7 (all p<0.05), due to both significant reductions in total number of IFNγ producing cells and amount of IFNγ produced per cell (all p<0.05). Importantly, IFNγ total expression on day 1 and 4 after admission could discriminate 180-day mortality better than absolute lymphocyte count (ALC), IL-6 and procalcitonin. Septic patients with low IFNγ expression were older and had lower ALC and higher sPD-L1 and IL-10 concentrations, consistent with an immune suppressed endotype.
A whole blood IFNγ ELISpot assay can both identify septic patients at increased risk of late mortality, and identify immune-suppressed, sepsis patients.
Details
- Title: Subtitle
- Adverse outcomes and an immune suppressed endotype in sepsis patients with reduced interferon-γ ELISpot
- Creators
- Evan L Barrios - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaMonty B Mazer - Department of Pediatrics, UH Rainbow Babies and Children's Hospital, Cleveland, United States of AmericaPatrick W McGonagill - University of IowaChristian B Bergmann - Universität UlmMichael D Goodman - University of CincinnatiRobert W Gould - University of Minnesota Medical SchoolMahil Rao - University of IowaValerie E Polcz - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaRuth Davis - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaDrew Del Toro - Department of Anesthesiology, Washington University School of Medicine, St. Louis, United States of AmericaMarvin Dirain - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaAlexandra Dram - Department of Anesthesiology, Washington University School of Medicine, St. Louis, United States of AmericaLucas Hale - University of Minnesota Medical SchoolMohammad Heidarian - University of IowaCaleb Y Kim - University of Minnesota Medical SchoolTamara A Kucaba - University of Minnesota Medical SchoolJennifer P Lanz - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaAshley McCray - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaAlexandra Meszaros - Department of Anesthesiology, Washington University School of Medicine, St. Louis, United States of AmericaSydney M Miles - Department of Anesthesiology, Washington University School of Medicine, St. Louis, United States of AmericaCandace Nelson - University of Minnesota Medical SchoolIvanna Rocha - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaElvia E Silva - University of IowaRicardo Ungaro - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaAndrew Walton - Department of Anesthesiology, Washington University School of Medicine, St. Louis, United States of AmericaJulie Xu - University of Minnesota Medical SchoolLeilani Zeumer-Spataro - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaAnne M Drewry - Department of Anesthesiology, Washington University School of Medicine, St. Louis, United States of AmericaMuxuan Liang - Department of Biostatistics, University of Florida College of Medicine, Gainesville, United States of AmericaLetita E Bible - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaTyler J Loftus - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaIsaiah R Turnbull - Department of Anesthesiology, Washington University School of Medicine, St. Louis, United States of AmericaPhilip A Efron - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaKenneth E Remy - Department of Pediatrics, UH Rainbow Babies and Children's Hospital, Cleveland, United States of AmericaScott C Brakenridge - University of Washington School of MedicineVladimir P Badovinac - University of IowaThomas S Griffith - University of Minnesota Medical SchoolLyle L Moldawer - Department of Surgery, University of Florida College of Medicine, Gainesville, United States of AmericaRichard S Hotchkiss - Department of Anesthesiology, Washington University School of Medicine, St. Louis, United States of AmericaCharles C Caldwell - University of Cincinnati
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.9(2), e175785
- DOI
- 10.1172/jci.insight.175785
- PMID
- 38100268
- PMCID
- PMC10906237
- NLM abbreviation
- JCI Insight
- eISSN
- 2379-3708
- Grant note
- DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: R01 GM-132364
- Language
- English
- Electronic publication date
- 12/15/2023
- Date published
- 01/23/2024
- Academic Unit
- Critical Care; Stead Family Department of Pediatrics; Pathology; Surgery; Internal Medicine
- Record Identifier
- 9984530281402771
Metrics
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