SLE is a chronic multisystem disease that is genetically associated with a deficiency of the C4A but not the C4B isotype of the fourth component of human complement.
Pathogenesis is attributed to the inadequate clearance and processing of immune complexes.
The importance of complement receptors and its ligands has been clearly demonstrated as CR1 and CR2 deficient mice have severe defects in both their innate and acquired immune responses. Evidence obtained in this laboratory suggests that immune complexes coated with C4A bind better to CR1 and are less likely to precipitate than C4B-coated immune complexes and that this is directly related to differential folding of the cognizant protein. The two isotypes of C4A and C4B have different conformations after nucleophilic scission of the thioester. Analysis of human C4A and C4B binding to an immune complex in serum. J. of Clin.