R E V I E W Anticomplement therapy Prathit A Kulkarni1 Vahid Afshar-Kharghan2 1Baylor College of Medicine, Houston, Texas, USA; 2The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA Correspondence: Vahid Afshar-Kharghan, M.D. Anderson Cancer Center, 2121 W. Holcombe Blvd., Suite 7.716, Unit 1100, Houston,TX 77030, USA Tel +1 713 563 5267 Fax +1 713 563 0411 Email vakharghan@mdanderson.org Abstract: The complement system is an important part of innate immunity; however, as with other parts of the immune system, the complement system can become pathologically activated and create or worsen disease. Anticomplement reagents have been studied for several years, but only recently have they emerged as a viable therapeutic tool. Here, we describe the role of the complement system in a wide array of diseases, as well as the use of anticomplement therapy as treatment for these diseases in animal models and in human clinical trials. Speciﬁcally, we will discuss the role of anticomplement therapy in paroxysmal nocturnal hemoglobinuria, glo- merulonephritis, and heart disease, including coronary artery disease, myocardial infarction, and coronary revascularization procedures such as percutaneous coronary angioplasty and coronary artery bypass graft surgery. Keywords: complement, paroxysmal nocturnal hemoglobinuria, glomerulonephritis, myocardial infarction, cardiopulmonary bypass Introduction The complement system, as a part of innate immunity, carries out a wide array of functions, including protection against foreign organisms, removal of immune complexes from the circulation, and clean-up of cellular debris which accumulates over time. The complement system also plays a signiﬁcant role in the initiation and propagation of the inﬂammatory response. Besides its beneﬁcial effect, though, the complement system can also play a detrimental role in many pathologic conditions. The complement system comprises several plasma and cell surface proteins, including complement regulatory proteins. When these complement regulatory proteins do not function properly, the complement system can become improperly activated and cause tissue damage. Over the last several years, a signiﬁcant amount of work has been done to study complement activation in certain disease states and whether there is any role for complement inhibition in the treatment of these diseases. In this paper, we will review the function and regulation of the complement system, give a brief description of various complement inhibitors, and discuss the recent use of anticomplement therapeutics in speciﬁc diseases, namely paroxysmal nocturnal hemoglobinuria, glomerulonephritis, and heart disease, including coronary artery disease, myocardial infarction, and cardiac surgery requiring the use of cardiopulmonary bypass. Overview of the complement system Activation of the complement system The complement system comprises more than 30 plasma proteins, most of which are synthesized by the liver. The complement system acts through three major pathways, the classical pathway, activated by antigen-antibody complexes; the alternative pathway, activated spontaneously by attachment of C3b to a particular surface; and the lectin pathway, activated by the binding of mannan-binding lectins to carbohydrate ligands on the surface of pathogens (Figure 1) (Janeway et al 1999; Qin and Gao 2006; Biologics: Targets & Therapy 2008:2(4) 671–685 © 2008 Kulkarni and Afshar-Kharghan, publisher and licensee Dove Medical Press Ltd.This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. 671