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Updated: May 19, 2026
06:29
Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
How immune complexes from certain IgG NAbs and any F(ab')₂ can mediate excessive complement activation
1Institute of Biochemistry, Swiss Federal Institute of Technology, ETH Hönggerberg, Zurich, Switzerland. hans.lutz@bc.biol.ethz.ch
Advances in Experimental Medicine and Biology
|August 21, 2012
Summary
Excessive immune complexes (IC) involving IgG or F(ab')₂ fragments drive sepsis mortality by amplifying complement activation. These ICs, particularly F(ab')₂-IC with anti-hinge antibodies, potently stimulate the complement cascade, leading to severe inflammation.
Area of Science:
- Immunology
- Complement System Biology
- Sepsis Pathophysiology
Background:
- Sepsis mortality is linked to excessive inflammation driven by the complement system, primarily through C3/C5 convertase activation.
- Immune complexes (IC), especially those containing IgG or F(ab andomIndex)₂ fragments, are key activators of complement amplification.
- The alternative pathway of complement is amplified by properdin, with C3b acting as a crucial component.
Purpose of the Study:
- To elucidate the mechanisms by which IgG-IC and F(ab andomIndex)₂-IC stimulate complement amplification in sepsis.
- To investigate the role of Fab affinity for C3 and the formation of secondary ICs in complement activation.
- To compare the potency of C3b₂-IgG-IC and C3b₂-F(ab andomIndex)₂-IC/anti-hinge NAbs in stimulating complement amplification.
Main Methods:
- Analysis of IgG-containing and F(ab andomIndex)₂-containing immune complexes (IC) in the context of complement activation.
- Investigation of the interaction between C3b and the Fab regions of IgG and F(ab andomIndex)₂ fragments.
- Characterization of secondary IC formation involving anti-hinge NAbs and F(ab andomIndex)₂-IC.
- Quantification of complement amplification stimulated by different IC types in conjunction with properdin.
Main Results:
- Both IgG-IC and F(ab andomIndex)₂-IC can capture dimeric C3b, acting as precursors for alternative C3 convertases.
- IgG-IC capture dimeric C3b via Fab affinity for C3, a property rare in natural antibodies (NAbs).
- F(ab andomIndex)₂-IC capture dimeric C3b when forming secondary ICs with anti-hinge NAbs, which rigidify the complex.
- C3b₂-IgG-IC and C3b₂-F(ab andomIndex)₂-IC/anti-hinge NAbs stimulate complement amplification up to 750 times more effectively than C3b and properdin alone.
- F(ab andomIndex)₂ fragments, generated during sepsis, evade Fc-receptor clearance, prolonging circulation and enhancing secondary IC formation.
Conclusions:
- Excessive complement amplification by specific immune complexes significantly contributes to sepsis-induced inflammation and mortality.
- F(ab andomIndex)₂-IC, particularly when forming secondary complexes, represent a potent pathway for complement overactivation in sepsis.
- Understanding these IC-mediated complement pathways offers potential therapeutic targets for managing sepsis.
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