The role of complement in the aetiopathogenesis of systemic lupus erythematosus.

The role of classical pathway complement components in systemic lupus erythematosus (SLE) is reviewed. Their importance in maintaining immune complexes (IC) in soluble form and in enhancing clearance of IC through binding to red cell CR1 is such that deficiency, complete or partial, of these components or some of their controlling enzymes can lead to IC mediated disease like SLE. C2 and C4 are encoded within the class III region of the major histocompatibility complex (MHC). There are certain well described associations between class II MHC genes and the occurrence of SLE and the relative importance of the two sets of gene products and their potential interactions are discussed. Complement C4 plays a role in drug induced lupus as many of the lupus associated drugs bind to C4 and interfere with its protective functions. Classical genetic studies provide clear evidence that non MHC genes are important in the aetiopathogenesis of SLE. Non MHC encoded complement deficiencies and functional deficits may well represent some of these other genetic factors and is clearly a fertile area for future research.