Immune Complex Handling in Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) has long been regarded as the paradigm for autoimmune disease mediated by immune complexes. The idea that SLE was an ‘immune-complex disease’ came from a variety of observations. Firstly, antigen-antibody complexes could be found in the serum of patients with active disease1. Secondly, active disease was frequently associated with hypocomplementaemia, thought to be due to systemic activation of the classical complement pathway by immune complexes. Thirdly, there was evidence for the deposition of immune complexes (ICs) in a number of organs, including joints, lung, brain and kidney. More specifically, localization of DNA-anti-DNA complexes in kidneys was described in a number of studies2–4. Based on the work of Cochrane, Germuth, Dixon and colleagues, in a variety of models of serum-sickness in the late 1950s and 1960s5, a hypothesis was developed—that the interaction of antigens and antibodies results in the formation of circulating immune complexes, and that deposition of such complexes in the tissues, with local activation of complement and other inflammatory mediators, produces injury. The observation in SLE of both circulating and tissue bound ICs fitted well with this hypotheses. However, recent studies of the immunopathological basis of antibody- and IC-mediated damage have suggested a more complex explanation for the role of immune complexes in SLE6.