Anti-factor B autoantibody in dense deposit disease

Dense deposit disease (DDD), also known as membranoproliferative glomerulonephritis type II, is a rare kidney disorder that is associated with dysregulation of the alternative pathway of complement. Autoantibodies against the C3bBb convertase termed C3 nephritic factor are common in DDD patients. Here we report an autoantibody that binds to complement factor B in a DDD patient who was negative for C3 nephritic factor. This anti-factor B autoantibody recognized an epitope within the Bb fragment and was able to bind to the C3bBb convertase. Upon binding, the anti-factor B autoantibody stabilized the convertase against both intrinsic and factor H-mediated extrinsic decay and thus enhanced C3 consumption. Functional analyses demonstrated that, in contrast to C3 nephritic factor, the anti-factor B autoantibody inhibited complement-mediated lysis in vitro due to inhibition of the C5 convertase and the terminal complement pathway. Analysis of C5a plasma levels indicated that not all C5 convertases are inhibited by the autoantibodies in the patient in vivo. Antigen array experiments confirmed the presence of anti-factor B autoantibodies and also revealed complement activating anti-C1q antibodies in the patient's plasma. In summary, the present report describes a new autoantibody in DDD that binds to factor B and to the alternative pathway C3 convertase and alters the kinetics of complement activation and regulation.