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Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
Activated complement is more extensively present in diseased aortic valves than naturally occurring complement
M ter Weeme1, A B A Vonk, K Kupreishvili
1OLVG, Amsterdam, The Netherlands.
Insights
Naturally occurring anti-complement mediators like C1-inhibitor and clusterin are present in diseased aortic valves. However, activated complement deposition exceeds inhibitor presence, suggesting ongoing inflammation in aortic valve disease.
Area of Science:
- Immunology
- Cardiovascular Pathology
Background:
- Complement system activation is implicated in aortic valve disease pathogenesis.
- The role of endogenous anti-complement mediators in this context remains unclear.
Purpose of the Study:
- To investigate the presence and distribution of activated complement and its inhibitors in various aortic valve pathologies.
- To analyze the balance between complement activation and inhibition in degenerative, atherosclerotic, and bacterial endocarditis affected aortic valves.
Main Methods:
- Human aortic valves (n=30) from autopsy, including controls and diseased samples (atherosclerosis, degeneration, bacterial endocarditis), were analyzed.
- Immunohistochemistry was used to detect activated complement (C3d, C5b9) and inhibitors (C1-inh, clusterin).
- Positivity areas were quantified for comparative analysis.
Main Results:
- Activated complement (C3d, C5b9) and inhibitors (C1-inh, clusterin) were detected in aortic valve endothelium and extracellular matrix.
- All mediators were present in controls, with significantly increased deposition in diseased valves, especially bacterial endocarditis.
- Complement deposition was significantly more widespread than inhibitor deposition across all disease types.
Conclusions:
- Diseased aortic valves exhibit co-deposition of activated complement and anti-complement mediators (C1-inh, clusterin), indicating a local counter-response.
- The greater extent of activated complement deposition compared to inhibitors suggests a potential mechanism for sustained inflammation in affected aortic valves.
Background:
Recent studies indicate a role for complement in the pathogenesis of aortic valve disease. However, the role of naturally occurring anti-complement mediators in this context is unknown. In this study, we have analysed this in three different pathological conditions of the aortic valve: degeneration, atherosclerosis and bacterial endocarditis.
Materials And Methods:
Human aortic valves were obtained at autopsy (n = 30): 5 control valves, 10 aortic valves with atherosclerotic changes, 10 aortic valves with degenerative changes and 5 degenerative changed aortic valves with bacterial infection. These valves were analysed immunohistochemically for the presence of activated complement (C3d and C5b9) and the complement inhibitors C1-inh and clusterin. Areas of positivity were then quantified.
Results:
C3d, C5b9 and the complement inhibitors C1-inh and clusterin depositions were mainly found in the endothelium and extracellular matrix in aortic valves. All these mediators were already present in control valves, but the area of positivity increased significantly in response to the different diseases, with the highest increase in response to bacterial endocarditis. Interestingly, in all three aortic diseases, the depositions of complement were significantly more widespread than that of their inhibitors.
Conclusions:
Our study indicates that anti-complement mediators (C1-inh and clusterin) are deposited in diseased aortic valves together with activated complement, indicating an existing counter response against complement locally in the valve. However, deposition of activated complement is significantly more widespread than that of its inhibitors, which could explain ongoing inflammation in those diseased aortic valves.
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