4.5 Article

Nucleosomes and C1q bound to glomerular endothelial cells serve as targets for autoantibodies and determine complement activation

Journal

MOLECULAR IMMUNOLOGY
Volume 49, Issue 1-2, Pages 75-83

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2011.07.020

Keywords

Systemic lupus erythematosus; Lupus nephritis; Autoantibodies; C1q; Nucleosomes

Funding

  1. Dutch Kidney Foundation [CO4.2077, KJPB 09.01]
  2. European Union [238756]
  3. MRC [G0800200] Funding Source: UKRI
  4. Medical Research Council [G0800200] Funding Source: researchfish

Ask authors/readers for more resources

Various studies indicate a role for both anti-nucleosome and anti-C1q autoantibodies in glomerulonephritis in patients with systemic lupus erythematosus. However, a causal relationship between these autoantibodies and the development of lupus nephritis has not been fully established. Since injury of the endothelium is a major target in lupus nephritis we assessed the interaction of C1q and nucleosomes with glomerular endothelial cells in vitro in the presence or absence of autoantibodies against these antigens. We demonstrate a direct and dose-dependent binding of both nucleosomes and C1q to immortalized human glomerular endothelial cells (GEnC) in vitro, which in part is mediated by cell surface heparan sulfate. We demonstrate that nucleosomes and C1q serve as targets for monoclonal and polyclonal antibodies as well as for anti-nuclear autoantibodies from patients with systemic lupus erythematosus. An additive effect of anti-C1q autoantibodies on anti-nucleosome mediated complement activation was observed. Furthermore, we showed that the activation of complement on glomerular endothelial cells is mediated by the classical pathway since the deposition of C3 on GEnC is abrogated by MgEGTA and does not occur in C1q-depleted serum. Taken together, our studies demonstrate a direct binding of both nucleosomes and C1q to glomerular endothelial cells in vitro. The subsequent binding of autoantibodies against nucleosomes in patients with systemic lupus erythematosus is potentially pathogenic and autoantibodies against C1q seem to have an additional effect. (C) 2011 Elsevier Ltd. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available