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Increased Alternative Complement Pathway Function and Improved Survival during Critical Illness.

William Bain1,2, Huihua Li3, Rick van der Geest1

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American Journal of Respiratory and Critical Care Medicine
|May 7, 2020
PubMed
Summary
This summary is machine-generated.

Elevated alternative complement pathway (AP) function in critically ill patients correlates with improved survival and reduced mortality. This enhanced immune capacity suggests AP plays a protective role in critical illness.

Keywords:
complementcritical illnesshost defensepneumoniaserum

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Area of Science:

  • Immunology
  • Critical Care Medicine
  • Complement System Biology

Background:

  • The complement system is vital for host defense but can contribute to detrimental inflammation in critical illness.
  • The role and function of the alternative complement pathway (AP), a key amplifier of complement activity, remain poorly understood in critically ill patients.

Purpose of the Study:

  • To investigate the function and essential components of the alternative complement pathway in critically ill patients.
  • To evaluate the association between alternative complement pathway activity and clinical outcomes, including mortality and survival.
  • To examine the alternative complement pathway's role in a mouse model of pneumonia.

Main Methods:

  • Quantified classical (CH50) and alternative complement (AH50) function in serum from 321 critically ill patients.
  • Measured alternative pathway (AP) regulatory factors (B, H, properdin) using ELISA and analyzed transcriptomics data from external cohorts.
  • Utilized wild-type, Cfb-/- , and C3-/- mice infected with Klebsiella pneumoniae (KP) to assess extrapulmonary dissemination.

Main Results:

  • Higher AH50 levels, but not CH50, were linked to decreased 30-day mortality (aOR, 0.53) and improved one-year survival (aHR, 0.59).
  • Elevated AH50 correlated with increased AP factors and a reduced 'hyperinflammatory' subphenotype (aOR, 0.30).
  • AP factor depletion or low AH50 impaired in vitro control of KP, and Cfb-/- mice showed increased dissemination and inflammation.

Conclusions:

  • Enhanced alternative complement pathway function is associated with improved survival in critical illness, suggesting a protective role.
  • The findings indicate that elevated AP activity may confer enhanced immune capacity, contributing to better patient outcomes.
  • The alternative complement pathway is a potential therapeutic target for improving outcomes in critical illness.