ABSTRACT
The ability of pooled normal human immunoglobulin (IgG) for intravenous use (IVIG) to inhibit complement1 was neither known before its clinical application nor expected. In fact, the opposite appeared more likely, because IVIG contains a huge variety of immune antibodies and a myriad of different naturally occurring autoantibodies (NAbs), capable of activating complement, when complexed with antigen. Some of these lowtiter, lowaffinity NAbs have tissue-homeostatic roles and do not exist in saturating conditions in human plasma2. Hence, an IVIG-induced increase in their concentration could enhance complement consumption in the course of additional clearance of altered and senescent self. Some evidence was presented for enhanced, isoagglutinin-independent clearance of red blood cells3, but the extent of an extra complement activation must have been minute, since the overall effect of IVIG is complement-inhibiting. To understand how IVIG may modulate complement, the following summarizes the relevant steps of complement activation.
