6 - Complement deficiency and systemic lupus erythematosus

Abstract

The exact etiology of systemic lupus erythematosus (SLE) is not known. Hereditary complement deficiency, especially deficiency of an early complement component of the classical pathway, is a genetic factor associated with SLE and SLE-like disease in humans and most recently in mouse models with “knockout” of these components. This chapter reviews the association of hereditary and acquired complement deficiency states with SLE and SLE-like disease. The emphasis is on clinical manifestations in patients with these deficiencies, the differences in many patients from classic SLE, and the implication of these differences for current hypotheses on the specific role of the early complement components in SLE. The discussion begins with a description of the complement system. Next, the biological activities and the associations of deficiencies of the complement system with disease are described to provide the context for this review on the early components. The genetics of complement components and the clinical manifestations of genetic and acquired complement deficiencies are then reviewed with the exception of the genetics of the C4 component of complement. The chapter concludes with a speculative discussion of the role of complement deficiency in SLE, including recent studies and hypotheses on the role of early complement components in apoptosis.