Adverse Long-Term Outcomes and an Immune Suppressed Endotype in Sepsis Patients with Reduced Interferon-γELISpot: A Multicenter, Prospective Observational Study.
Adverse Long-Term Outcomes and an Immune Suppressed Endotype in Sepsis Patients with Reduced Interferon-γELISpot: A Multicenter, Prospective Observational Study.
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干扰素减少的脓毒症患者的长期不良结果和免疫抑制内型 - γELISpot：一项多中心、前瞻性观察研究。
DOI：
10.1101/2023.09.13.23295360
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发表时间：
2023
期刊：
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L
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作者：
Barrios,EvanA;Mazer,MontyB;McGonagill,Patrick;Bergmann,ChristianB;Goodman,MichaelD;Gould,Robert;Rao,Mahil;Polcz,Valerie;Davis,Ruth;DelToro,Drew;Dirain,Marvin;Dram,Alexandra;Hale,Lucas;Heidarian,Mohammad;Kucaba,TamaraA;L
脓毒症仍然是一个主要的临床挑战，成功的治疗需要更高的精确度来识别不良结果风险增加的患者，需要不同的治疗方法。预测脓毒症患者的临床结果和免疫内分泌分型通常依赖于使用血液蛋白或mRNA生物标记物，或静态细胞表型。方法对来自5个学术卫生中心的10 7例败血症患者和68例非败血症患者于入院后第1、4、7天采集血样，采用活血全血酶联免疫吸附试验检测干扰素-γ的细胞产生情况。结果与46例健康受试者相比，脓毒症患者和非败血症患者的未刺激和刺激的全血干扰素γ表达分别增加或不变。然而，在未存活180天的脓毒症患者中，刺激的全血干扰素γ的表达在ICU的第1、4和7天显著减少(均P<0.05)，这是由于产生干扰素γ−的细胞总数和每细胞产生的干扰素γ的数量均显著减少(均P<0.05)。重要的是，干扰素γ在入院后第1天和第4天的总表达比淋巴细胞绝对计数、IL-6和降钙素原更能区分180d的死亡率。低干扰素γ表达的脓毒症患者年龄较大，ALC较低，Spd-L1和IL-10浓度较高，与免疫抑制内型一致。结论全血干扰素γELISpot试验既可以识别晚期死亡风险增加的脓毒症患者，也可以识别免疫抑制的脓毒症患者。
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 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.MethodsAnex vivowhole 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.ResultsCompared 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.ConclusionsA whole blood IFNγ ELISpot assay can both identify septic patients at increased risk of late mortality, and identify immune-suppressed, sepsis patients.Trial RegistryBecause the study is a prospective observational study, and not a clinical trial, registration withclinical trials.govis not required.