Complement activation in severely ill patients with sepsis: no relationship with inflammation and disease severity

被引:21
作者
de Nooijer, Aline H. [1 ,2 ,3 ]
Kotsaki, Antigone [4 ]
Kranidioti, Eleftheria [5 ]
Kox, Matthijs [2 ,3 ]
Pickkers, Peter [2 ,3 ]
Toonen, Erik J. M. [6 ]
Giamarellos-Bourboulis, Evangelos J. [4 ]
Netea, Mihai G. [1 ,3 ,7 ]
机构
[1] Radboud Univ Nijmegen, Dept Internal Med, Med Ctr, Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Dept Intens Care Med, Med Ctr, Nijmegen, Netherlands
[3] Radboud Univ Nijmegen, Radboud Univ Med Ctr Infect Dis, Radboud Univ Med Ctr, Med Ctr, Nijmegen, Netherlands
[4] Natl & Kapodistrian Univ Athens, Dept Internal Med 4, Athens, Greece
[5] Evangelismos Gen Hosp, Dept Internal Med 5, Athens, Greece
[6] R&D Dept, Hycult Biotechnol, Uden, Netherlands
[7] Univ Bonn, Life & Med Sci Inst, Dept Immunol & Metab, Bonn, Germany
基金
欧盟地平线“2020”; 欧洲研究理事会;
关键词
Sepsis; Inflammation; Complement; Septic shock; Mortality; DEFINITIONS;
D O I
10.1186/s13054-023-04344-6
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
BackgroundSepsis 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.MethodsSecondary 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.ResultsThe 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.ConclusionsOnce 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.
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页数:6
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