Anti-C1q antibodies are present in 30%–40% of patients with SLE (Seelen et al 2003). One might conclude based on these various, then, that the early components of the complement system are probably necessary for normal homeostasis of the immune system and that their absence may predispose to the development of immune-complex disease. Thus, targeting later components of the complement system for anticomplement therapy in glomerulonephritis may be the best option (Berger and Daha 2007). Therapy The clinical trials of anticomplement agents in patients with kidney disease have been much more limited than those in PNH patients. Nonetheless, many in vitro experiments and animal studies have been conducted in various types of glomerulonephritis. Couser et al studied complement inhibition in three different animal models of complement- mediated glomerulonephritis (Couser et al 1995). In these models, administration of sCR1 was able to reduce the morphologic and functional characteristics of renal disease, as measured by mesangiolysis, glomerular inﬁltration by platelets and macrophages, and proteinuria. In a mouse model of immune-complex-mediated glomerulonephritis, a monoclonal antibody against C5, BB5.1, was able to lessen renal disease and prolong survival (Wang et al 1996). The same antibody was also able to reduce proteinuria and renal damage in mice subjected to human antidouble-stranded DNA (Ravirajan et al 2004). In a mouse model of antimyeloperoxidase IgG-induced glomerulonephritis, administration of anti-C5 antibody (BB5.1) thwarted the development of glomerular disease, as shown by decreased hematuria, pyuria, albuminuria, and glomerular neutrophil inﬁltration (Huugen et al 2007). In a multicenter, randomized, placebo-controlled phase II trial conducted in the US on 122 patients with idiopathic membranous nephropathy, treatment with eculizumab did not decrease urinary protein excretion, the primary outcome goal of the study (Appel et al 2002). However, there was some beneﬁt with eculizumab in the open-label extension of the study. Currently, there is an ongoing trial with eculizumab in patients with membranous nephropathy; the results of this trial are still pending (Berger et al 2005; Javaid and Quigg 2005; Brown et al 2007). Coronary heart disease Coronary artery disease (CAD) is one of the most common causes of morbidity and mortality in the United States and Biologics:Targets & Therapy 2008:2(4) Anticomplement therapy the world at large. A signiﬁcant amount of work has been done to better understand the role of the complement system in the pathology and pathophysiology of atherosclerosis and myocardial infarction (MI). This work has culminated in several clinical trials which have tested anticomplement therapy in the setting of acute myocardial infarction (AMI) and cardiac surgery. Stable coronary artery disease Overview and pathophysiology It has long been known that the complement system is involved in the development of CAD. For example, even in the late 1970’s and throughout the 1980’s, it was repeatedly shown that C3 is present in atherosclerotic plaques (Hollander et al 1979; Hansson et al 1984; Vlaicu et al 1985). Interestingly, complement regulatory proteins, including CR1, complement receptor 3, DAF, and CD59 are also present in atherosclerotic plaques, thus demonstrating activity and regulation of the complement system in atherosclerotic plaques (Seifert and Hansson 1989a, 1989b; Seifert et al 1992). More recently, it was shown that C3 levels may be a good marker of insulin resistance, a risk factor for the development of diabetes mellitus (DM), and CAD (Muscari et al 2000). The level of C3 was a better predictor of blood pressure and glucose levels than the level of insulin itself. C3 levels also have an independent, signiﬁcant correlation with ﬁbrinogen levels, body mass indices, platelet counts (important for the development of thrombi), insulin levels, triglyceride (TG) levels, and levels of low-density lipoprotein cholesterol (Capuano et al 2006). To our knowledge, no clinical trials using anticomplement therapies have been conducted in patients with stable CAD. However, we describe this work because it is relevant to potential clinical studies that could be done in patients with CAD. Acute myocardial infarction Overview and pathophysiology Involvement of the complement system in AMI has been shown since the 1970’s. It was ﬁrst observed that administration of CVF 30 min prior to occlusion of the left anterior descending coronary artery in dogs reduced necrosis and neutrophil inﬁltration into the myocardium (Maroko et al 1978). The complement proteins C3, C4, and C5 were deposited on infarcted tissue in a baboon model of AMI, and Laine et al showed that there was extensive deposition of iC3b in ruptured plaques, as compared to nonruptured plaques, from human coronary arteries in patients who had 677