C1q (460 kDa), a highly conserved protein, is part of the first component of the complement system. The biological function of C1q is to bind immune complexes via its six globular domains and of a variety of other "non-immune" activators of the complement system, including CRP, DNA, fibronectin, fibrinogen, and lipopolysaccharides, by its collagen-like region (CLR). In immune complexes, C1q is normally bound to Fc regions of IgG in order to fulfill the activation function of C1q within the classical pathway . For many years, C1q was therefore used in radioimmunoassays and ELISAs to detect circulating immune complexes (CIC) in numerous diseases, including SLE [157-159]. In SLE, the CIC titers determined by C1q assays correlated well with disease activity and renal involvement. However, an alternative means of binding C1q has also been described for use in cases where high-affinity autoantibodies directly recognize the CLR of C1q through the antibody F(ab) antigen-combining sites rather than via the Fc domain. Since they were first described [160-162], anti-C1q auto-antibodies have been commonly identified in patients with autoimmune diseases such as SLE, rheumatoid vasculitis, MCTD, Felt/s syndrome, ankylosing spondylitis, polyarteritis, mixed cryoglobulinemia, membranoproliferative glomerulonephritis, glomerulosclerosis, anti-glomerular basement membrane nephritis, and hypocomplementemic urticarial vasculitis syndrome [163-165].
Anti-C1q autoantibodies are thought to be closely associated with nephritis in SLE. IgG anti-C1q autoantibodies correlate with nephritis, hypocomplemente-mia, and anti-dsDNA autoantibodies [166-168]. Because significant increases in serum anti-C1q autoantibody titers precede clinical manifestation of nephritis, they have a predictive value . Recently, anti-C1q autoantibodies were identi-
fied postmortem in the glomeruli of four of five patients with proliferative glomerulonephritis. The concentrations of these autoantibodies in the glomerular tissue was at least 50 times higher than the serum concentration; this is the first evidence suggesting that anti-C1q autoantibodies collect and concentrate in the renal glomeruli of patients with SLE. Therefore, anti-C1q autoantibodies may contribute to the pathogenesis of lupus glomerulonephritis [170, 171]. Conversely, lupus nephritis does not develop in the absence of anti-C1q autoantibodies, [172, 173]. Anti-C1q autoantibodies also occur in murine models of SLE [174, 175]. A recent study showed that anti-C1q antibodies cause renal pathologies in combination with glomerular C1q-containing immune complexes .
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