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Updated: Mar 9, 2026
Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
Complement activation in relation to capillary leakage in children with septic shock and purpura
J A Hazelzet1, R de Groot, G van Mierlo
1Divisions of Pediatric Intensive Care, Department of Pediatrics, Sophia Children's Hospital/University Hospital Rotterdam, The Netherlands. hazelzet@alg.azr.nl
Insights
Complement activation, indicated by specific markers, is linked to severe meningococcal sepsis outcomes. Higher levels of complement activation products correlate with increased disease severity and mortality in children.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Infectious diseases
Background:
- Sepsis, particularly meningococcal sepsis, is a leading cause of mortality in children.
- Capillary leakage and inflammatory mediators play crucial roles in sepsis pathogenesis.
- The role of complement activation in severe meningococcal sepsis and its association with outcomes requires further elucidation.
Purpose of the Study:
- To investigate the relationship between capillary leakage and inflammatory mediators in children with severe meningococcal sepsis.
- To identify specific inflammatory markers and complement activation products associated with disease severity and mortality.
- To explore the potential of complement activation as a therapeutic target in meningococcal sepsis.
Main Methods:
- Blood samples collected from 52 children with severe meningococcal sepsis at admission, 24h, and 72h.
- Analysis of cytokines (IL-6, IL-8), neutrophil degranulation markers (elastase, lactoferrin), complement activation products (C3a, C3b/c, C4b/c, C3-CRP, C4-CRP), and complement regulators (C1 inhibitor, C4BP).
- Assessment of capillary leakage via plasma infusion volume and disease severity using the Pediatric Risk of Mortality (PRISM) score.
Main Results:
- Significantly different levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP were observed between survivors and non-survivors upon admission.
- C3b/c levels were 2.2 times higher in non-survivors, while C3-CRP levels were 1.9 times higher in survivors.
- Mortality was independently associated with elevated C3b/c and C3-CRP complex levels, which correlated with PRISM score and capillary leakage.
Conclusions:
- Complement activation is significantly associated with a poor outcome and a more severe disease course in children with severe meningococcal sepsis.
- Specific complement activation products, such as C3b/c and C3-CRP complexes, are predictive of mortality.
- Further research into complement activation as a potential therapeutic target for meningococcal sepsis is warranted.
Abstract:
To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.
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