Time-Dependent Variation in Immunoparalysis Biomarkers Among Patients with Sepsis and Critical Illness

Abigail Samuelsen, Parker Burrows, Erik Lehman, Anthony S Bonavia
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Abstract

Immunoparalysis is a significant concern in patients with sepsis and critical illness, potentially leading to increased risk of secondary infections. This study aimed to perform a longitudinal assessment of immune function over the initial two weeks following the onset of sepsis and critical illness. We compared ex vivo stimulated cytokine release to traditional markers of immunoparalysis, including monocyte Human Leukocyte Antigen (mHLA)-DR expression and absolute lymphocyte count (ALC). A total of 64 critically ill patients were recruited in a tertiary care academic medical setting, including 31 septic and 33 non-septic patients. Results showed that while mHLA-DR expression significantly increased over time, this was primarily driven by the non-septic subset of critically ill patients. ALC recovery was more prominent in septic patients. Ex vivo stimulation revealed significant increases in TNF and IL-6 production over time in septic patients. However, IFNg production varied with the stimulant used and did not show significant recovery when normalized to cell count. No significant correlation was found between mHLA-DR expression and other immunoparalysis biomarkers. These findings suggest the need for more nuanced immune monitoring approaches beyond the traditional 'sepsis' versus 'non-sepsis' classifications in critically ill patients. It also provided further evidence of a potential window for targeted immunotherapeutic interventions in the first week of critical illness.
败血症和危重症患者免疫分析生物标志物的时间依赖性变化
脓毒症和危重症患者的免疫功能低下是一个值得关注的问题,有可能导致继发感染的风险增加。本研究旨在对败血症和危重症患者发病后最初两周的免疫功能进行纵向评估。我们将体内外刺激细胞因子的释放与免疫分析的传统指标(包括单核细胞人类白细胞抗原(mHLA)-DR表达和绝对淋巴细胞计数(ALC))进行了比较。在一家三级医疗学术机构共招募了 64 名重症患者,包括 31 名败血症患者和 33 名非败血症患者。结果显示,随着时间的推移,mHLA-DR的表达量明显增加,但这主要是由非败血症重症患者亚群驱动的。脓毒症患者的 ALC 恢复更为明显。体内外刺激显示,随着时间的推移,脓毒症患者体内 TNF 和 IL-6 的产生量明显增加。然而,IFNg的产生随所用刺激物的不同而变化,并且在与细胞计数归一化时没有显示出明显的恢复。mHLA-DR 表达与其他免疫分析生物标志物之间没有发现明显的相关性。这些发现表明,除了传统的 "败血症 "和 "非败血症 "分类外,还需要对危重病人进行更细致的免疫监测。它还进一步证明,在危重病人发病的第一周,可能是进行有针对性的免疫治疗干预的窗口期。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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