ArticleJCI insight2024
Adverse outcomes and an immunosuppressed endotype in septic patients with reduced IFN-γ ELISpot.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Progressive Decline in Interferon-γ Release is Associated with Cirrhosis Progression and Severity: A Prospective Preliminary Report.Annals of laboratory medicine · 2026Article
- Host-directed immune therapies: a second front in the battle against sepsis.The Journal of clinical investigation · 2026Review
- Monitoring T-cell function in septic shock: one-year experience with a fully automated assay.Critical care (London, England) · 2026Observational
- Temporal variability in healthy donor IFN-γ ELISpot responses reveals a stable IL-7-responsive functional metric for immune phenotyping.ImmunoHorizons · 2026Article
- Quantifying Nuance Within Sepsis-Associated Immune Suppression Toward Diagnostic Certainty.Shock (Augusta, Ga.) · 2026Article
- Interferon-gamma to interleukin-10 ratio is negatively associated with short-term mortality risk in sepsis patients: a retrospective study based on immune balance index.Frontiers in immunology · 2026Article
- Monocyte Anisocytosis Can Discriminate Between Sepsis and Sterile Inflammation, but not Mortality, in Critically Ill Surgical/Trauma Patients: A Secondary Prospective Analysis.Critical care explorations · 2025Observational
- IFNγ in human sepsis: a scoping review.Annals of intensive care · 2025Review
- Determining potential immunomodulatory drug efficacy in sepsis using ELISpot.Scientific reports · 2025Article
- FUNCTIONAL IMMUNOPHENOTYPING FOR PRECISION THERAPIES IN SEPSIS.Shock (Augusta, Ga.) · 2025Review
- Dynamic functional assessment of T cells reveals an early suppression correlating with adverse outcome in polytraumatized patients.Frontiers in immunology · 2025Article
- New Criteria for Pediatric Sepsis: A Phoenix Rising.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2024Article
- Development and optimization of a diluted whole blood ELISpot assay to test immune function.Journal of immunological methods · 2024Observational
- Predicting Organ Dysfunction in Septic and Critically Ill Patients: A Prospective Cohort Study Using Rapid Ex Vivo Immune Profiling.Critical care explorations · 2024Observational
- Surviving septic patients endotyped with a functional assay demonstrate active immune responses.Frontiers in immunology · 2024Observational
- Immunotherapy in the context of sepsis-induced immunological dysregulation.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
40 authors at 10 institutions in 2 countries.
Funding
Abstract
BACKGROUNDSepsis 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 generally relies on using blood protein or mRNA biomarkers, or static cell phenotyping. Here, we sought to determine whether functional immune responsiveness would yield improved precision.METHODSAn ex vivo whole-blood enzyme-linked immunosorbent spot (ELISpot) assay for cellular production of interferon γ (IFN-γ) was evaluated in 107 septic and 68 nonseptic patients from 5 academic health centers using blood samples collected on days 1, 4, and 7 following ICU admission.RESULTSCompared with 46 healthy participants, unstimulated and stimulated whole-blood IFN-γ expression was either increased or unchanged, respectively, in septic and nonseptic ICU patients. However, in septic patients who did not survive 180 days, stimulated whole-blood IFN-γ expression was significantly reduced on ICU days 1, 4, and 7 (all P < 0.05), due to both significant reductions in total number of IFN-γ-producing cells and amount of IFN-γ produced per cell (all P < 0.05). Importantly, IFN-γ total expression on days 1 and 4 after admission could discriminate 180-day mortality better than absolute lymphocyte count (ALC), IL-6, and procalcitonin. Septic patients with low IFN-γ expression were older and had lower ALCs and higher soluble PD-L1 and IL-10 concentrations, consistent with an immunosuppressed endotype.CONCLUSIONSA whole-blood IFN-γ ELISpot assay can both identify septic patients at increased risk of late mortality and identify immunosuppressed septic patients.TRIAL REGISTRYN/A.FUNDINGThis prospective, observational, multicenter clinical study was directly supported by National Institute of General Medical Sciences grant R01 GM-139046, including a supplement (R01 GM-139046-03S1) from 2022 to 2024.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.