The role of complement in antibody therapy for infectious diseases

The complement system is part of the innate immune system, eliciting central immunoregulatory functions. Detection of foreign surfaces is either achieved through complement-specific patternrecognition molecules or mediated by antigen recognition of antibodies. Immunoglobulin A (IgA), IgG, and IgM all have the potential to initiate a complement response, with the efficiency and response development closely related to the antibody isotype, multimeric state, and degree of glycosylation. A group of serum proteins constitutes the central effector functions of complement, thus allowing direct cell lysis, opsonization, and inflammation. These effector functions can be used in antibody therapies, especially against infectious diseases, as the target membranes lack complement regulatory proteins. The relative contribution of each function and the interplay with direct antibody-mediated clearance is not fully exploited, thus suggesting an option for further rational optimization of antibody therapies.