Preprint
Adverse Long-Term Outcomes and an Immune Suppressed Endotype in Sepsis Patients with Reduced Interferon-γ ELISpot: A Multicenter, Prospective Observational Study
medRxiv
Cold Spring Harbor Laboratory
09/13/2023
DOI: 10.1101/2023.09.13.23295360
PMCID: PMC10516075
PMID: 37745385
Abstract
Background 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.
Methods 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.
Results 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.
Conclusions 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 Long-Term Outcomes and an Immune Suppressed Endotype in Sepsis Patients with Reduced Interferon-γ ELISpot: A Multicenter, Prospective Observational Study
- Creators
- Evan A BarriosMonty B. Mazer - Case Western Reserve UniversityPatrick McGonagill - University of IowaChristian B. Bergmann - University of Cincinnati Medical CenterMichael D. Goodman - University of Cincinnati Medical CenterRobert W. GouldMahil Rao - University of IowaValerie Polcz - University of FloridaRuth Davis - Florida CollegeDrew Del Toro - Washington University in St. LouisMarvin Dirain - University of FloridaAlexandra Dram - Washington University in St. LouisLucas Hale - University of Minnesota Medical CenterMohammad Heidarian - University of IowaTamara A. Kucaba - University of Minnesota Medical CenterJennifer P. Lanz - University of FloridaAshley McCray - University of FloridaSandra MeszarosSydney Miles - Washington University in St. LouisCandace Nelson - University of Minnesota Medical CenterIvanna RochaElvia E Silva - University of IowaRicardo Ungaro - University of FloridaAndrew Walton - Washington University in St. LouisJulie Xu - University of Minnesota Medical CenterLeilani Zeumer-Spataro - Florida CollegeAnne M. Drewry - Washington University in St. LouisMuxuan Liang - Florida CollegeTyler Loftus - Florida CollegeIsaiah Turnbull - Washington University in St. LouisPhilip A. Efron - University of FloridaKenneth E. Remy - Case Western Reserve UniversityScott Brakenridge - Harborview Medical CenterVladimir P Badovinac - University of IowaThomas S. Griffith - University of Minnesota Medical CenterLyle L. Moldawer - University of FloridaRichard S. Hotchkiss - Washington University in St. LouisCharles C. Caldwell - University of Cincinnati Medical Center
- Resource Type
- Preprint
- Publication Details
- medRxiv
- DOI
- 10.1101/2023.09.13.23295360
- PMID
- 37745385
- PMCID
- PMC10516075
- Publisher
- Cold Spring Harbor Laboratory
- Language
- English
- Date posted
- 09/13/2023
- Academic Unit
- Critical Care; Stead Family Department of Pediatrics; Pathology; Surgery; Internal Medicine
- Record Identifier
- 9984472658902771
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