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Adverse outcomes and an immunosuppressed endotype in septic patients with reduced IFN-γ ELISpot.
Barrios, Evan L; Mazer, Monty B; McGonagill, Patrick W; Bergmann, Christian B; Goodman, Michael D; Gould, Robert W; Rao, Mahil; Polcz, Valerie E; Davis, Ruth J; Del Toro, Drew E; Dirain, Marvin Ls; Dram, Alexandra; Hale, Lucas O; Heidarian, Mohammad; Kim, Caleb Y; Kucaba, Tamara A; Lanz, Jennifer P; McCray, Ashley E; Meszaros, Sandra; Miles, Sydney; Nelson, Candace R; Rocha, Ivanna L; Silva, Elvia E; Ungaro, Ricardo F; Walton, Andrew H; Xu, Julie; Zeumer-Spataro, Leilani; Drewry, Anne M; Liang, Muxuan; Bible, Letitia E; Loftus, Tyler J; Turnbull, Isaiah R; Efron, Philip A; Remy, Kenneth E; Brakenridge, Scott C; Badovinac, Vladimir P; Griffith, Thomas S; Moldawer, Lyle L; Hotchkiss, Richard S; Caldwell, Charles C.
Afiliación
  • Barrios EL; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Mazer MB; Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • McGonagill PW; Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
  • Bergmann CB; Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
  • Goodman MD; University Hospital Ulm, Clinic for Trauma Surgery, Hand, Plastic, and Reconstructive Surgery Albert-Einstein-Allee 23, Ulm, Germany.
  • Gould RW; Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
  • Rao M; Department of Anesthesiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Polcz VE; Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
  • Davis RJ; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Del Toro DE; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Dirain ML; Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Dram A; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Hale LO; Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Heidarian M; Department of Anesthesiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Kim CY; Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
  • Kucaba TA; Department of Urology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Lanz JP; Department of Urology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • McCray AE; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Meszaros S; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Miles S; Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Nelson CR; Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Rocha IL; Department of Anesthesiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Silva EE; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Ungaro RF; Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
  • Walton AH; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Xu J; Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Zeumer-Spataro L; Department of Urology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Drewry AM; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Liang M; Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Bible LE; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Loftus TJ; Department of Biostatistics, University of Florida College of Public Health and Health Professions and the University of Florida College of Medicine, Gainesville, Florida, USA.
  • Turnbull IR; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Efron PA; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Remy KE; Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Brakenridge SC; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Badovinac VP; Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Griffith TS; Department of Surgery, Harborview Medical Center, University of Washington School of Medicine, Seattle, Washington, USA.
  • Moldawer LL; Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
  • Hotchkiss RS; Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
  • Caldwell CC; Experimental Pathology PhD Program, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
JCI Insight ; 9(2)2024 Jan 23.
Article en En | MEDLINE | ID: mdl-38100268
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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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Interferón gamma / Sepsis Idioma: En Revista: JCI Insight Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Interferón gamma / Sepsis Idioma: En Revista: JCI Insight Año: 2024 Tipo del documento: Article