Research subject: The role of complement in human disease.

Complement is part of the innate immune system protecting the host against invading micro-organisms. Regulatory control mechanisms normally prevent the system from extensive and systemic activation, thereby protecting the host from self damage. Under various disease conditions complement is improperly activated, either locally leading to tissue damage or systemically with risk of serious homeostatic disturbances. A primary research goal for the Complement Research Group is to elucidate the role of complement as a primary inducer of the inflammatory reaction and thereby form a basis for a future therapeutic approach in complement-mediated disease processes. For this purpose we have developed novel assays for detection and quantification of complement activation products based on monoclonal antibodies to activation dependent epitopes on a number of complement components; the most important one being the assay for TCC (the terminal SC5b-9 complement complex). These assays are used to detect complement activation experimentally and clinically and to evaluate the effect of various complement inhibitors in experimental models. In a novel in vitro human whole blood model where all potential inflammatory mediators are able to interact mutually, we are currently studying the effect of complement inhibition on a number of arms of the inflammatory network. Current clinical and experimental animal projects focus on allo- and xenotransplant rejection, pulmonary dysfunction and systemic inflammatory response syndrome of the newborn, infection and septicaemia, ischemia-reperfusion injury, biocompatibility of extracorporeal circulation devices, and rheumatic tissue damage.