Background 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. Methods 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. Results 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). Conclusion 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.

中文翻译：

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不同病原体、感染部位和不良结局的感染性休克患者的单核细胞 HLA-DR 表达动力学

背景 单核细胞 (m)HLA-DR 表达降低是脓毒症诱导的免疫抑制的研究最多的生物标志物。迄今为止，关于败血症特征（例如感染部位、致病病原体或疾病严重程度）与 mHLA-DR 表达动力学之间的关系知之甚少。方法我们评估了 241 名感染性休克患者的 mHLA-DR 表达动力学，这些患者具有不同的原发感染部位和病原体。此外，我们使用无监督聚类分析来识别 mHLA-DR 轨迹并评估它们与结果参数的关联。结果在感染部位不同的患者组之间（腹部与呼吸道，p = 0.13；腹部与泌尿道，p = 0.53）和病原体类别（革兰氏阳性与非感染）之间，未发现 mHLA-DR 表达动力学存在差异。革兰氏阴性，p = 0.54；革兰氏阳性与阴性培养物，p = 0.84）。幸存者和非幸存者的 mHLA-DR 表达动力学不同 (p < 0.001)，仅在幸存者中随时间增加。此外，我们确定了三个 mHLA-DR 轨迹（“早期改进者”、“延迟或非改进者”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果（继发性感染或死亡）概率更高（延迟或非改善者对数秩 p = 0.03，调整后的风险比 2.0 [95% CI 1.0– 4.0]，p = 0.057，下降者对数秩 p = 0.01，调整后的风险比为 2.8 [95% CI 1.1–7.1]，p = 0.03）。结论 感染性休克患者的原发感染部位或致病病原体与 mHLA-DR 表达动力学无关。然而，与显示出 mHLA-DR 表达迅速增加的患者相比，显示出 mHLA-DR 表达延迟或无改善或下降的患者出现不良结果的风险更高。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值，对脓毒性休克患者具有临床重要性。