Novel roles of complement in systemic lupus erythematosus--hypothesis for a pathogenetic vicious circle.

We propose that impaired complement function enhances a pathogenetic vicious circle in SLE. In this process, induction and clearance of apoptotic cells is central. Apoptosis could be triggered by various etiological factors, such as infection, UV light, and drug reactions. Clearance of apoptotic material is reduced when complement function is impaired. Apoptosis leads to increased exposure of nuclear antigens to the immune system, to which estrogenic hormones could contribute. This could in turn lead to activation of autoreactive B cells, autoantibody production, and immune complex formation, all of which is accelerated by hypocomplementemia. Immune complexes may, at least partly via complement dependent mechanisms, accelerate apoptosis.