Fisler Grace, Brewer Mariana R, Yaipen Omar, Deutschman Clifford S, Taylor Matthew D
Cohen Children's Medical Center, Northwell, New Hyde Park, NY, United States.
Northwell, Division of Pediatric Critical Care Medicine, New Hyde Park, NY, United States.
Front Immunol. 2025 Jan 28;16:1527142. doi: 10.3389/fimmu.2025.1527142. eCollection 2025.
The immune response changes as patients age, yet studies on the immune dysregulation of sepsis often do not consider age as a key variable.
We hypothesized that age would influence the immune response in septic children and that there would be a distinct variation in the immune profile in healthy children and children with either sepsis, uncomplicated infection, or acute organ dysfunction without infection. We characterized the circulating immune profile of children presenting to our tertiary care children's hospital.
This investigation was a prospective, observational cohort study that enrolled patients from July 2020 - September 2022. Patients were included if they were < 21 years, admitted to the PICU, and received fluid resuscitation and antibiotics. Peripheral blood mononuclear cells were isolated from samples collected on PICU day 1.
Eighty patients were enrolled. Children with sepsis had more regulatory CD4 T cells and memory CD4 T cells and less CD4IL-10 and CD8T-bet T cells than healthy children. After stimulation, sepsis samples had less of a reduction in CD4 T cells producing IL-10 than healthy controls. Memory CD4 T cells and regulatory CD4 T cells were positively associated with age in sepsis alone.
A regulatory T cell failure may contribute to pediatric sepsis pathogenesis. Age is an important variable affecting sepsis-associated immune dysregulation and memory T cells in peripheral circulation correlate with age in sepsis alone.
免疫反应会随着患者年龄的增长而变化,但关于脓毒症免疫失调的研究通常不将年龄视为关键变量。
我们假设年龄会影响脓毒症患儿的免疫反应,并且健康儿童与患有脓毒症、单纯感染或无感染的急性器官功能障碍的儿童的免疫特征会存在明显差异。我们对在我们的三级护理儿童医院就诊的儿童的循环免疫特征进行了表征。
本研究为前瞻性观察队列研究,纳入了2020年7月至2022年9月的患者。纳入标准为年龄小于21岁、入住儿科重症监护病房(PICU)并接受液体复苏和抗生素治疗的患者。在PICU第1天采集的样本中分离出外周血单个核细胞。
共纳入80例患者。与健康儿童相比,脓毒症患儿的调节性CD4 T细胞和记忆性CD4 T细胞更多,而CD4IL-10和CD8T-bet T细胞更少。刺激后,脓毒症样本中产生IL-10的CD4 T细胞减少幅度小于健康对照组。仅在脓毒症中,记忆性CD4 T细胞和调节性CD4 T细胞与年龄呈正相关。
调节性T细胞功能衰竭可能导致小儿脓毒症的发病机制。年龄是影响脓毒症相关免疫失调的重要变量,并且仅在脓毒症中,外周循环中的记忆性T细胞与年龄相关。