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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Leendert A Trouw
  • Tom Groeneveld
  • Marc A Seelen
  • Jacques M G J Duijs
  • Ingeborg M Bajema
  • Frans A Prins
  • Uday Kishore
  • David J Salant
  • J Sjef Verbeek
  • Cees van Kooten
  • Mohamed R Daha
Externa organisationer
  • External Organization - Unknown
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Annan medicinsk grundvetenskap
Originalspråkengelska
Sidor (från-till)679-688
TidskriftJournal of Clinical Investigation
Volym114
Utgivningsnummer5
StatusPublished - 2004
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa