The complement system in lupus nephritis

Abstract

The complement is part of the innate immune system and can be activated through one of three pathways. To prevent injury of self-tissue, complement is tightly regulated by over 30 proteins. Complement plays dual roles in the pathogenesis of systemic lupus erythematosus (SLE). On one hand, hereditary homozygous deficiencies of classical pathway components, such as C1q and C4, are associated with an increased risk for SLE, suggesting that complement is protective. On the other hand, complement is systemically consumed in both experimental and human SLE, suggesting its pathogenic role.  Studies in genetically altered mice have shown that lack of complement inhibitors, such as complement factor H (CFH) or decay-accelerating factor (DAF) accelerates the development of experimental lupus nephritis; while treatment with recombinant protein inhibitors such as CR1-related protein y (Crry)-Ig, CR2-Crry, CR2-DAF and CR2-CFH ameliorates the disease development.  Complement-targeted drugs, including soluble complement receptor 1 (TP10), C1 esterase inhibitor (C1-INH), and a monoclonal anti-C5 antibody (Eculizumab) have been shown to inhibit complement safely, and are now being investigated in a variety of clinical conditions. These clinical developments support their therapeutic use in lupus nephritis.