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C3 activation products, C3 containing immune complexes, the terminal complement complex and native C9 in patients
U Olmez1, P Garred, T E Mollnes
1Institute of Immunology and Rheumatology, National Hospital, Oslo, Norway.
Insights
Complement activation is significantly higher in rheumatoid arthritis (RA) joints, with elevated C3 products and immune complexes in synovial fluid (SF). This highlights the need for neoepitope detection in RA diagnostics.
Area of Science:
- Immunology
- Rheumatology
- Biochemistry
Background:
- Rheumatoid arthritis (RA) involves joint inflammation where complement system activation may play a role.
- Assessing complement activation in synovial fluid (SF) can provide insights into local joint pathology.
Purpose of the Study:
- To evaluate complement activation products, specifically C9 and C3-containing immune complexes (CIC), in the SF and plasma of RA and osteoarthritis (OA) patients.
- To determine the significance of local complement activation within the joints of RA patients.
Main Methods:
- Analysis of complement activation products (C9, C3-CIC) in plasma and SF samples.
- Comparison of complement levels between RA patients, OA patients, and potentially healthy controls (implied).
- Correlation analysis between complement activation markers and CIC levels.
Main Results:
- Synovial fluid (SF) from RA patients showed significantly higher levels of C3 activation products and terminal complement complexes (5-8 times plasma levels).
- Native C9 concentration was lower in SF compared to plasma, suggesting excessive local complement consumption.
- Elevated CIC levels in RA SF correlated with the degree of local complement activation.
Conclusions:
- The findings strongly support substantial local complement cascade activation within the joints of RA patients.
- Detecting C3 activation via neoepitope expression is emphasized over single fragment analysis for diagnostic accuracy.
- Increased CIC levels are linked to the extent of complement activation in RA joints, indicating their potential as biomarkers.
Abstract:
Complement activation products, C9 and C3-containing circulating immune complexes (CIC), were evaluated in plasma and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis. C3 activation products and the fluid phase terminal complement complex were considerably elevated in SF from RA patients reaching levels five- to eighttimes that in plasma, consistant with a local activation of the whole cascade in the joints. The results emphazise the importance of detecting C3 activation by neoepitope expression instead of single fragment determinations. The concentration of native C9 was lower in synovial fluid compared with plasma, consistant with the excessive local complement activation. Increased CIC levels which correlated with the degree of complement activation were also found in the SF from the RA patients.