In the absence of C1q, or when C1q is low due to immune complex-mediated complement consumption, the high level of HMGB1 in SLE patients may skew to M1 macrophage polarization unchecked, promoting inflammation and further reducing clearance of apoptotic cells, exposing autoantigens and thus creating a favorable environment for the adaptive immune system to generate autoantibodies. The gene discussed is HMGB1; the disease is systemic lupus erythematosus.