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Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes

Trouw, Leendert A; Groeneveld, Tom LU ; Seelen, Marc A; Duijs, Jacques M G J; Bajema, Ingeborg M; Prins, Frans A; Kishore, Uday; Salant, David J; Verbeek, J Sjef and van Kooten, Cees, et al. (2004) In Journal of Clinical Investigation 114(5). p.679-688
Abstract
Anti-C1q autoantibodies are present in sera of patients with several autoimmune diseases, including systemic lupus erythematosus (SLE). Strikingly, in SLE the presence of anti-C1q is associated with the occurrence of nephritis. We have generated mouse anti-mouse C1q mAb's and used murine models to investigate whether anti-C1q autoantibodies actually contribute to renal pathology in glomerular immune complex disease. Administration of anti-C1q mAb JL-1, which recognizes the collagen-like region of C1q, resulted in glomerular deposition of C1q and anti-C1q autoantibodies and mild granulocyte influx, but no overt renal damage. However, combination of JL-1 with a subnephritogenic dose of C1q-fixing anti-glomerular basement membrane (anti-GBM)... (More)
Anti-C1q autoantibodies are present in sera of patients with several autoimmune diseases, including systemic lupus erythematosus (SLE). Strikingly, in SLE the presence of anti-C1q is associated with the occurrence of nephritis. We have generated mouse anti-mouse C1q mAb's and used murine models to investigate whether anti-C1q autoantibodies actually contribute to renal pathology in glomerular immune complex disease. Administration of anti-C1q mAb JL-1, which recognizes the collagen-like region of C1q, resulted in glomerular deposition of C1q and anti-C1q autoantibodies and mild granulocyte influx, but no overt renal damage. However, combination of JL-1 with a subnephritogenic dose of C1q-fixing anti-glomerular basement membrane (anti-GBM) antibodies enhanced renal damage characterized by persistently increased levels of infiltrating granulocytes, major histological changes, and increased albuminuria. This was not observed when a non-C1q-fixing anti-GBM preparation was used. Experiments with different knockout mice showed that renal damage was dependent not only on glomerular C1q and complement activation but also on Fcgamma receptors. In conclusion, anti-C1q autoantibodies deposit in glomeruli together with C1q but induce overt renal disease only in the context of glomerular immune complex disease. This provides an explanation why anti-C1q antibodies are especially pathogenic in patients with SLE. (Less)
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type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Investigation
volume
114
issue
5
pages
679 - 688
publisher
The Journal of Clinical Investigation
external identifiers
  • pmid:15343386
  • scopus:4944245001
ISSN
0021-9738
DOI
10.1172/JCI200421075
language
English
LU publication?
no
id
c7e0927b-9f3f-46d9-984a-736f13b88170 (old id 1130513)
date added to LUP
2008-06-18 15:54:52
date last changed
2017-12-10 04:34:33
@article{c7e0927b-9f3f-46d9-984a-736f13b88170,
  abstract     = {Anti-C1q autoantibodies are present in sera of patients with several autoimmune diseases, including systemic lupus erythematosus (SLE). Strikingly, in SLE the presence of anti-C1q is associated with the occurrence of nephritis. We have generated mouse anti-mouse C1q mAb's and used murine models to investigate whether anti-C1q autoantibodies actually contribute to renal pathology in glomerular immune complex disease. Administration of anti-C1q mAb JL-1, which recognizes the collagen-like region of C1q, resulted in glomerular deposition of C1q and anti-C1q autoantibodies and mild granulocyte influx, but no overt renal damage. However, combination of JL-1 with a subnephritogenic dose of C1q-fixing anti-glomerular basement membrane (anti-GBM) antibodies enhanced renal damage characterized by persistently increased levels of infiltrating granulocytes, major histological changes, and increased albuminuria. This was not observed when a non-C1q-fixing anti-GBM preparation was used. Experiments with different knockout mice showed that renal damage was dependent not only on glomerular C1q and complement activation but also on Fcgamma receptors. In conclusion, anti-C1q autoantibodies deposit in glomeruli together with C1q but induce overt renal disease only in the context of glomerular immune complex disease. This provides an explanation why anti-C1q antibodies are especially pathogenic in patients with SLE.},
  author       = {Trouw, Leendert A and Groeneveld, Tom and Seelen, Marc A and Duijs, Jacques M G J and Bajema, Ingeborg M and Prins, Frans A and Kishore, Uday and Salant, David J and Verbeek, J Sjef and van Kooten, Cees and Daha, Mohamed R},
  issn         = {0021-9738},
  language     = {eng},
  number       = {5},
  pages        = {679--688},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes},
  url          = {http://dx.doi.org/10.1172/JCI200421075},
  volume       = {114},
  year         = {2004},
}