Immune deposition of C1q and anti-C1q antibodies in the kidney is dependent on the presence of glomerular IgG.
Anti-C1q autoantibodies are found frequently in patients with Systemic Lupus Erythematosus (SLE) and several studies indicate that these autoantibodies are associated with renal involvement. We have shown earlier that administration of anti-C1q antibodies to normal BALB/c mice results in the deposition of these antibodies and C1q in the kidney. In the present study we have investigated which factors are essential for this C1q-anti-C1q deposition. Injection of anti-C1q antibodies in C57BL/6 mice results in deposition of both C1q and anti-C1q in glomeruli, while administration of equal concentrations of anti-C1q to immunoglobulin deficient Rag2-/- mice did not result in deposition of anti-C1q antibodies. Analysis of renal sections of naive Rag2-/- mice revealed absence of mouse IgG and C1q in the glomeruli, while circulating C1q was within normal levels. Reconstitution of Rag2-/- mice with IgG, either by injection with purified mouse IgG or by splenocyte transfer, resulted in restored localization of mouse IgG together with C1q in the kidney. Subsequent injection of anti-C1q antibodies in these IgG reconstituted mice resulted in clear deposition of C1q together with anti-C1q in the kidneys comparable to that found in C57BL/6 mice receiving anti-C1q. We propose that the continuous presence of serum derived non-immune IgG in the glomerulus serves as a target for low affinity interactions with C1q, which then can serve as antigen for anti-C1q antibodies. Therefore we hypothesize that high and fluctuating levels of IgG as observed in patients with SLE may contribute to flares of renal inflammation in those patients with anti-C1q autoantibodies.
Trouw
L A
LA
Department of Nephrology, D3-P-39 Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. latrouw@lumc.nl
Duijs
J M G J
JM
van Kooten
C
C
Daha
M R
MR
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex / Q000032:analysis*; D001323:Autoantibodies; D015922:Complement C1q / Q000032:analysis*; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis*; D007668:Kidney / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007074:Immunoglobulin G; D015922:Complement C1q