Kulkarni and Afshar-Kharghan the period of time of the study. Hemoglobin stabilization without transfusion occurred in 21 of 43 patients in the eculizumab group, while it occurred in 0 of 44 patients in the placebo group. A median of 10 units of blood were given to the placebo group during the study period, while the group receiving eculizumab required 0 units. In addition, the eculizumab group had a signiﬁcant decrease in LDH levels as well as a signiﬁcant increase in quality of life. In a multinational open-label extension study of the TRI- UMPH study using 195 patients, the same authors studied the effect of eculizumab on the occurrence of thromboembolism (TE) (Hillmen et al 2007). Prior to treatment, the TE event rate was 7.37/100 patient-years, whereas with treatment, the rate was 1.07/100 patient-years. It was thus concluded that treatment with eculizumab in PNH signiﬁcantly reduces the occurrence of TE. Another possible option for the treatment of PNH is recombinant soluble CD59, since this is one of the critical membrane-bound proteins deﬁcient in PNH. In vitro studies with human PNH erythrocytes showed that recombinant soluble CD59 was able to bind to the surface of RBCs at levels sufﬁcient to inhibit complement-mediated hemolysis (Hill et al 2006). In an in vivo experiment, the RBCs of mice given recombinant soluble CD59 were partially protected from complement-mediated destruction. In a similar experi- ment, a single-chain antibody variable region fragment tar- geted against TER-119, a mouse RBC antigen, was attached to human DAF (Spitzer et al 2004). This recombinant protein was able to bind to mouse RBCs in vivo and protect them from complement-mediated destruction. Glomerulonephritis Overview and pathophysiology The basic pathophysiology of glomerulonephritis is inflammation of the glomerulus, and the main clinical features of the various glomerulonephritides include proteinuria, hematuria, and decreased glomerular function (Javaid and Quigg 2005). End-stage renal disease can be the eventual outcome of glomerulonephritis, which leaves patients dependent on chronic dialysis and/or renal transplantation. The complement system can play a signiﬁcant role in the inﬂammation of glomerulonephritis. For example, greater than 80% of patients with Type II membranoproliferative glomerulonephritis (MPGN) are positive for serum C3-nephritic factor, an antibody against C3bBb which inhibits the dissociation of Bb from C3b (Daha et al 1976; Schwertz et al 2001). In patients with IgM nephropathy, 676 serum C3 levels are directly correlated with proteinuria and progression of the disease (Myllymäki et al 2006). The important role of the complement system in the development of different glomerular diseases has been shown in several animal models. Mice deﬁcient in FH develop Type II MPGN with deposition of C3 in the capillary walls (Pickering et al 2002). Of interest, mice deﬁcient in FH and C5 developed less severe disease than those only deﬁcient in FH (Pickering et al 2006). Mice deficient in either DAF or DAF and CD59 had an increased incidence of immune-complex- mediated glomerulonephritis with increased glomerular deposition of C3 (Bao et al 2007). In a mouse model of immune-complex-mediated glomerulonephritis, CD59-deficient mice had more proteinuria (Turnberg et al 2003). Similarly, DAF-deficient mice and DAF- and CD59-combined knockout mice had much worse albuminuria in a model of nephrotoxic serum-induced nephritis (Lin et al 2004). In another mouse model of progressive glomerlonephritis, C5a receptor (C5aR)-deﬁcient mice showed less interstitial damage than control mice (Welch et al 2002). Similarly, in a mouse model of lupus nephritis, a synthetic anti-C5a receptor molecule (a cyclic hexapeptide) led to less decline in renal function, as well as decreased inﬁltration of kidneys by neutrophils and macrophages (Bao et al 2005). Despite the etiologic role of the complement system in the pathogenesis of the majority of the glomerulone- phritides, in some cases, a functional complement system might play a protective role against the development of glomerulonephritis. For example, factor D-deficient mice, which lack the alternative complement system, developed immune-complex glomerulonephritis (specifically Type II rapidly progressive glomerulonephritis) and showed mesangial deposition of IgM (Abrera-Abeleda et al 2007). Complement activity is necessary for the clearance of immune complexes from the body, and lack of this clearance activity due to a deficiency in complement activity might contribute to the development of glomerulonephritis. Another example of complement’s protective role in glomerulonephritis is that deficiencies in C1q, C2, or C4 predispose humans to the development of systemic lupus erythematosus (SLE) and lupus nephritis (Mitchell et al 2002). Presence of anti-C1q antibodies, resulting in the lack of a functional classical complement pathway, predicts with relatively high sensitivity and specificity the presence of active lupus nephritis (Moroni et al 2001; Trendelenburg et al 2006). Biologics:Targets & Therapy 2008:2(4)