The
complement system is a key part of the innate immune system and plays an important role in the clearance of pathogens and apoptotic cells upon its activation. It is well known that both
IgG and
IgM can activate
complement via the classical pathway by binding of C1q to the Fc regions of these
immunoglobulins. Recent advances have shown that also
IgA is capable of activating the
complement system. Besides, more insight is gained into an additional role for
antibodies in the activation of both the alternative and the
lectin pathways. Mouse models have shown that auto-
antibodies can activate the alternative pathway and induce in cell lysis and tissue damage. Besides the role of
antibodies in complement activation,
complement may also be a target for recognition by
antibodies directed against autologous
complement components. These auto-
antibodies play a role in several diseases, especially
vascular diseases. Understanding how
antibodies interact with the
complement system will allow the manipulation of this interaction to diminish pathological consequences of auto-
antibodies and optimize the effect of therapeutic
antibodies. In the current review, we discuss complement activation by (auto-)
antibodies by the different pathways.