Chapter 12 - The Complement System in Systemic Lupus Erythematosus

Abstract

Complement is intimately engaged in systemic lupus erythematosus (SLE). Here, we provide a comprehensive account of how complement is involved in the etiology, disease onset, pathogenesis, diagnosis, and management of human SLE. We have two primary objectives. The first is to summarize the current status and our thoughts about using complement as a biomarker to facilitate clinical management of SLE. The second is to summarize our knowledge on how genetic deficiency of complement contributes causatively to disease onset, and functional insufficiency of complement because of genetic polymorphisms or acquired protein deficiencies increases the predisposition and modifies the disease course and outcomes. The field of complement research in SLE is entering an exciting time with a wealth of new information on (a) crystal and solution structures of native and activated complement individual proteins as well as that of large molecular complexes, (b) identification of genetic variants and their functional consequences in predisposing to lupus, (c) utility of complement inhibitors to ameliorate complement-mediated tissue injuries, and (d) clinical trials using hematopoietic stem cells to cure SLE because of complement deficiency. Complement research has provided important breakthroughs relative to the etiology and pathogenesis of SLE. Hopefully, therapeutic interventions relative to modulating complement's role will favorably impact this chronic disease that affects millions of individuals.