C1 activation, with C1q in excess of functional C1 in synovial fluid from patients with rheumatoid arthritis
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Increased free C1q in rheumatoid arthritis synovial fluid suggests intra-articular complement activation. This was linked to low C1 and C4 levels, indicating complement system involvement in the disease.
Area of Science:
- Immunology
- Rheumatology
- Complement System
Background:
- Rheumatoid arthritis (RA) is a chronic inflammatory disease.
- The complement system plays a role in inflammation and immune responses.
- Understanding complement activation in RA joints is crucial for therapeutic strategies.
Purpose of the Study:
- To investigate the presence and significance of complement component C1q in the synovial fluid of rheumatoid arthritis patients.
- To explore the activation pathways of the complement system within the joint in RA.
- To differentiate complement activation patterns between RA and other arthritic conditions.
Main Methods:
- Analysis of synovial fluid and serum samples from patients with rheumatoid arthritis, osteoarthritis, and spondylarthritic syndromes.
- Quantification of complement components including free C1q, hemolytic C1, C4, and C3dg/d fragments.
- Immunochemical characterization of complement complexes in synovial fluid and serum.
Main Results:
- Elevated levels of functionally active free C1q were found in the synovial fluid of RA patients.
- Low concentrations of hemolytic C1 and C4, along with increased C3dg/d fragments, were associated with free C1q in RA synovial fluid.
- Intra-articular C1 activation was suggested, with distinct properties of synovial fluid C1r-C1s-C1 inactivator complexes compared to serum complexes.
- Control groups (osteoarthritis, spondylarthritic syndromes) showed no evidence of intra-articular complement activation, except for one case of Reiter's disease.
Conclusions:
- The findings strongly suggest intra-articular complement activation via the classical pathway in rheumatoid arthritis.
- Dissociation of C1 into free C1q and complexes containing C1r, C1s, and C1 inactivator occurs within the joint.
- Complement activation appears specific to RA among the studied arthritic conditions, highlighting its potential role in RA pathogenesis.
Abstract:
Free Clq, in functionally active form was present in increased amounts in the synovial fluid of patients with rheumatoid arthritis. The presence of free Clq was associated with low concentrations of hemolytic C1, low C4 and raised amounts of C3dg/d fragments in the synovial fluid. The findings suggested intra-articular C1 activation with dissociation of C1 into free C1q and complexes containing C1r, C1s, and C1 inactivator. However, the immunochemical properties of synovial fluid C1r-C1s-C1 inactivator complexes appeared to differ from those of the complexes formed in serum, which hampered quantification with the assay used. Control patients with osteoarthritis or spondylarthritic syndromes did not show evidence of intra-articular complement activation, even though 1 patient with Reiter's disease had unexplained low concentrations of synovial fluid C4 and C3. The concentrations of circulating complement components were largely normal in the patients. Slightly increased concentrations of free C1q and C1r-C1s-C1 inactivator complexes in serum and C3dg/d fragments in EDTA plasma were observed, particularly in the patients with rheumatoid arthritis.