Suspicion of congenital or acquired complement deficiency and complement activation. Further investigation and follow-up of SLE and glomerulonephritis.
Complement function is reported as a percentage of normal sera.
The complement system is a part of the immune defense. It strengthens the function of the antibodies and contributes to the killing of bacteria. Three pathways of activating the complement system are known: the classical, the alternative and the MBL pathway. (MBL=Mannan binding lectin). The classical pathway is activated by immune complexes, which is the case in SLE. C1q then binds to C1r and C1s and this triggers a cascade where C2 and C4 form a complex which cleaves C3. The alternative pathway is activated by formation of a complex between C3 and factor B through a reaction that especially occurs on the surface of bacteria. The MBL pathway is activated by a reaction between MBL and certain carbohydrates, which are found only in certain bacteria.
When measuring complement activation in vitro, a measure is obtained of the ability of the serum to activate the complement system through a certain pathway. The activation rate is a measure of the serum concentration of the components that are contained in the activating pathway. If the patient has a total lack of a component, the activation of that pathway becomes zero. In a patient with an active SLE disease, an activation of the classical pathway often occurs. This leads to a depletion of the components (C1q, C1s, C1r, C2, C4, C3 and C5-9). Serum from this patient is likely to have a reduced ability to activate the classical pathway in vitro. As some components are shared with the other pathways, their ability to be activated may be reduced because of the depletion of the components of the classical pathway. Complement activation is the most common cause of low levels of C3 and C4 in the circulation. Hereditary total deficiencies of complement factors (except for MBL) are rare.