Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Crit Care. 2023 Feb 16;27(1):63. doi: 10.1186/s13054-023-04344-6.
Sepsis is characterized by a dysregulated immune response to infection. The complement system plays an important role in the host defence to pathogens. However, exaggerated complement activation might contribute to a hyperinflammatory state. The interplay between complement activation and inflammation in relationship with adverse outcomes in sepsis patients is unclear.
Secondary analysis of complement factors in a prospective study in 209 hospitalized sepsis patients, of whom the majority presented with shock. Concentrations of complement factors C3, C3a, C3c, C5, C5a, and soluble terminal complement complex were assessed in ethylenediaminetetraacetic acid plasma samples collected within 24 h after sepsis diagnosis using enzyme-linked immunosorbent assays.
The concentration of complement factors in plasma of severely ill sepsis patients indicated profound activation of the complement system (all P < 0.01 compared to healthy controls). Spearman rank correlation tests indicated consistent relationships between the different complement factors measured, but no significant correlations were observed between the complement factors and other inflammatory biomarkers such as leukocyte numbers, C-reactive protein and ferritin concentrations, or HLA-DR expression on monocytes. The concentration of complement factors was not associated with Sequential Organ Failure Assessment score, the incidence of septic shock, and mortality rates (all P > 0.05) in this cohort of patients with high disease severity.
Once an infection progresses to severe sepsis or septic shock, the complement pathway is already profoundly activated and is no longer related to a dysregulated inflammatory response, nor to clinical outcome. This implies that in this patient category with severe disease, the complement system is activated to such an extent that it no longer has predictive value for clinical outcome.
败血症的特征是对感染的免疫反应失调。补体系统在宿主防御病原体中起着重要作用。然而，补体的过度激活可能导致过度的炎症状态。补体激活与炎症之间的相互作用与败血症患者的不良结局的关系尚不清楚。
对 209 例住院败血症患者的前瞻性研究中的补体因子进行二次分析，其中大多数患者出现休克。在败血症诊断后 24 小时内，使用酶联免疫吸附试验，从采集的乙二胺四乙酸血浆样本中评估补体因子 C3、C3a、C3c、C5、C5a 和可溶性末端补体复合物的浓度。
严重败血症患者的血浆中补体因子的浓度表明补体系统的深度激活（与健康对照组相比，所有 P 值均<0.01）。Spearman 等级相关检验表明，所测量的不同补体因子之间存在一致的关系，但补体因子与其他炎症生物标志物（如白细胞计数、C 反应蛋白和铁蛋白浓度，或单核细胞上 HLA-DR 表达）之间未观察到显著相关性。在这个疾病严重程度高的患者队列中，补体因子的浓度与序贯器官衰竭评估评分、败血性休克的发生率和死亡率均无关（均 P>0.05）。
一旦感染进展为严重败血症或败血性休克，补体途径已经被深度激活，并且不再与失调的炎症反应相关，也与临床结局无关。这意味着在这个疾病严重的患者群体中，补体系统被激活到如此程度，以至于它对临床结局不再具有预测价值。
