Limitations with determination of C3 and C4
There are a number of clinical situations where assessment of complement function is relevant. In many cases merely the level of C3 and C4 is measured immunochemically, as it is assumed that the concentrations of these complement components reflect the overall functionality of the complement system.
This view is oversimplification since simple determination of the levels of C3 and C4 is associated with serious limitations.
- There is a significant variation in the concentration of both C3 and C4 in normal individuals which also may overlap the concentration in many disease states.
- Most immunochemical methods used do not discriminate between native molecules C3 and C4 and the larger fragments formed during activation, C3b and C3c derived from C3 and C4b and C4c from C4.
- The condition of the liver is important since the synthesis of a majority of complement proteins including C3 and C4 takes place in this organ.
- During inflammation the acute phase reaction increases the synthesis of C3 and C4 which may counter-balance a concurrent consumption during complement activation.
- Simple immunochemical determination of the proteins may actually not reflect their functionality.
- Genetic variation may result in primary deficiency which may be interpreted as consumption during disease flares.
- Tissue deposition of immune complexes may lead to local complement activation, not revealed in the circulation.
- Any deficiency downstream from C3/C4 and several other complement deficiencies will go undetected if only C3 and C4 is measured.
Thus, single determination of the serum concentrations of C3 and C4, may not truthfully reflect overall complement function. In contrast, functional assays of the complement activation pathways such as the Svar Life Science complement ELISA, based on quantifying the formation of the Membrane Attack Complex, will reflect all the different steps in the complement activation pathways and hence the function.