Conceptual framework for progression of lupus nephritis. An inflammatory reaction is brought about by complement- or Fc-mediated responses to autoantibodies in deposited immune complexes or locally exposed danger signals (such as necrotic chromatin; see text), triggering release of MMPs from intrinsic and infiltrating cells. Increased proteolytic degradation of the membrane exposes matrix components, facilitating binding of autoantibodies to capillary and mesangial antigens. This maintains the inflammatory reaction and continued stimulation of matrix degradation, leading to disruption of glomerular membrane barriers and progression toward end-stage renal failure. MMP, matrix metalloproteinase.