Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Crit Care. 2020 Mar 20;24(1):110. doi: 10.1186/s13054-020-2830-x.
Decreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics.
We evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters.
No differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories ('early improvers', 'delayed or non-improvers' and 'decliners'). The probability for adverse outcome (secondary infection or death) was higher in the delayed or non-improvers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 [95% CI 1.0-4.0], p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 [95% CI 1.1-7.1], p = 0.03).
Sites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shock patients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shock patients.
单核细胞（m）HLA-DR 表达降低是脓毒症引起免疫抑制的最常用生物标志物。迄今为止，人们对脓毒症特征（如感染部位、病原体和疾病严重程度）与 mHLA-DR 表达动力学之间的关系知之甚少。
我们评估了 241 例不同感染部位和病原体的脓毒性休克患者的 mHLA-DR 表达动力学。此外，我们使用无监督聚类分析来识别 mHLA-DR 轨迹，并评估它们与预后参数的关系。
不同感染部位（腹部与呼吸道，p=0.13；腹部与泌尿道，p=0.53）和病原体类别（革兰阳性菌与革兰阴性菌，p=0.54；革兰阳性菌与阴性培养物，p=0.84）的患者组之间，mHLA-DR 表达动力学无差异。幸存者和非幸存者之间的 mHLA-DR 表达动力学存在差异（p<0.001），只有幸存者随时间增加。此外，我们鉴定了三种 mHLA-DR 轨迹（“早期改善者”、“延迟或非改善者”和“下降者”）。与早期改善者相比，延迟或非改善者和下降者的不良结局（继发感染或死亡）的可能性更高（延迟或非改善者对数秩检验 p=0.03，调整后的危险比为 2.0 [95%CI 1.0-4.0]，p=0.057；下降者对数秩检验 p=0.01，调整后的危险比为 2.8 [95%CI 1.1-7.1]，p=0.03）。
原发感染部位或病原体与脓毒性休克患者的 mHLA-DR 表达动力学无关。然而，与 mHLA-DR 表达迅速增加的患者相比，mHLA-DR 表达延迟或无改善或下降的患者不良结局的风险更高。我们的研究表明，mHLA-DR 表达随时间的变化而不是绝对值或静态测量，在脓毒性休克患者中具有临床重要性。
