| Systemic lupus erythematosus (SLE) is considered to be the prototype of immune complex (IC) diseases in man. It is thought that the complement system plays a major role in the regulation of formation and clearance of IC. Compatible with these observations is the finding that homozygous C1q deficiency is asssociated with a greater that 90% revalence of severe disease. We and others have reported that autoantibodies against C1q are found in 35-40% of patients with SLE who do not have a primary deficiency of C1q. In these patients a strong association between the occurrence of anti-C1q antibodies and renal involvement was found. More recently Mannik and co-workers demonstrated that eluates of kidneys from patients with SLE contain autoantibodies specific for C1q. These findings are in line with our observations that human C1q, when administered intraperitoneally to rats or mice, is transiently deposited in the glomerulus and that this glomerular C1q is stabilized when anti-C1q autobodies are present. The working hypothesis therefore is that under normal conditions C1q is trapped transiently in the glomerular basement membrane and when autoantibodies are present stabilization of deposition occurs followed by initiation of inflammation. Until now it was not possible to determine the role of anti-C1q antibodies in the development and maintenace of renal disease because no homologous anti-C1q antibodies were available to use in an animal model. The generation of transgenic mice with C1q deficiency has now permitted the development of a large number of mouse monoclonal antibodies with specificity for mouse C1q. The availability of these antibodies now offers the possibility to assess the role of anti-C1q antibodies in the development and maintenance of renal disease in the short and long term. |
