The relative merits of therapies being developed to tackle inappropriate (‘self’-directed) complement activation

The complement system is an enzyme cascade that helps defend against infection. Many complement proteins occur in serum as inactive enzyme precursors or reside on cell surfaces. Complement components have many biologic functions and their activation can eventually damage the plasma membranes of cells and some bacteria. Although a direct link between complement activation and autoimmune diseases has not been found, there is increasing evidence that complement activation significantly contributes to the pathogenesis of a large number of inflammatory diseases that may have autoimmune linkage. The inhibition of complement may therefore be very important in a variety of autoimmune diseases since their activation may be detrimental to the individual involved. However, a complete and long-term inhibition of complement may have some contra side effects such as increased susceptibility to infection. The site of complement activation will, however, determine the type of inhibitor to be used, its route of application and dosage level. Compared with conventional drugs, complement inhibitors may be the best option for treatment of autoimmune diseases. The review takes a critical look at the relative merits of therapies being developed to tackle inappropriate complement activation that are likely to result in sporadic autoimmune diseases or worsen already existing one. It covers the complement system, general aspects of complement inhibition therapy, therapeutic strategies and examples of complement inhibitors. It concludes by highlighting on the possibility that a better inhibitor of complement activation when found will help provide a formidable treatment for autoimmune diseases as well as preventing one.