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Determination of complement breakdown fragments C3d and its subfragments in health and disease
Insights
The study identifies a specific breakdown product, C3d3, of the complement system
Area of Science:
- Immunology
- Biochemistry
Background:
- The third component of complement (C3) plays a crucial role in the immune system.
- Measuring C3 breakdown products can indicate complement system activation and consumption.
Purpose of the Study:
- To investigate the breakdown products of C3.
- To characterize specific C3 subfragments and their clinical relevance.
- To assess the diagnostic potential of C3 breakdown products in autoimmune diseases.
Main Methods:
- Analysis of approximately 400 samples using rocket immunoelectrophoresis and two-dimensional electrophoresis.
- Quantification of C3d levels and identification of its subfragments (C3d1, C3d2, C3d3).
Main Results:
- Confirmed that C3d levels reflect complement consumption.
- Identified three novel subfragments: C3d1, C3d2, and C3d3.
- C3d3 was a predominant fragment in plasma from patients with autoimmune diseases, particularly systemic lupus erythematosus.
- C3d3 was found in limited amounts in normal plasma and sera, even after in vitro activation.
- Postsurgical patients showed C3d3, but C3d2 was more prevalent.
Conclusions:
- The C3d level is a valuable indicator of complement consumption.
- The C3d3 subfragment is a potential biomarker for chronic complement activation, likely driven by immune complexes.
- C3d3 may aid in diagnosing and monitoring autoimmune conditions characterized by sustained complement activation.
Abstract:
The breakdown products of the third component of complement in approximately 400 samples were measured by rocket immunoelectrophoresis and two-dimensional electrophoresis using the method of Brandslund et al [3]. It was confirmed that the measurement of the C3d level provides useful information on increased C3 consumption irrespective of the synthetic rate. Furthermore, three subfragments with C3d but without C3c antigenicity were distinguished, which were designated as C3d1, C3d2, and C3d3. The subfragment C3d3 which migrated to the most anodal side was a predominant component in the plasma from patients with autoimmune diseases. Little C3d3 subfragment was detected in normal plasma and in normal sera incubated in vitro for 24 hr. Even in the normal sera converted completely in vitro which contained little intact C3, only a limited amount of C3d3 was detected. In the plasma from postsurgical patients in whom activation of the complement system was considered to be in an acute phase, C3d3 was detected, but the C3d2 level was higher than the C3d3 level. In the plasma from patients with systemic lupus erythematosus having the normal C3d level, C3d3 was a major fragment. It is predicted that the preponderant presence of C3d3 in plasma could be the result of chronic continuous complement activation by immune complexes.