Anti-C1q autoantibodies specific against the globular domain of the C1qB-chain from patient with lupus nephritis inhibit C1q binding to IgG and CRP

Immunobiology. 2012 Jul;217(7):684-91. doi: 10.1016/j.imbio.2011.11.007. Epub 2011 Nov 28.

Abstract

Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus. Higher titers of serum anti-C1q autoantibodies correlate with disease activity in patients with lupus nephritis. Anti-C1q autoantibodies have been shown to bind neo-epitopes within the collagen region of human C1q. In a preliminary study, we recently reported that the anti-C1q autoantibodies could also recognize epitopes within the globular domain (gC1q) of the C1q molecule. Here, 38 sera from patients with renal biopsy-proven lupus nephritis were screened for the presence of anti-gC1q autoantibodies, using recombinant globular head regions of individual A (ghA), B (ghB) and C (ghC) chains of human C1q. We isolated anti-gC1q autoantibodies from three selected patients. Human C1q was pre-incubated with increasing concentrations of the isolated anti-ghA, anti-ghB or anti-ghC autoantibodies and its binding to different C1q target molecules such as IgG and CRP was then evaluated. Anti-ghB, but not anti-ghA and anti-ghC autoantibodies, markedly inhibited C1q interaction with IgG as well as CRP. These results appear to suggest that the anti-ghB autoantibodies may partially induce acquired functional C1q deficiency and thus may interfere with the biological function of C1q.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoantibodies / pharmacology
  • Binding Sites, Antibody
  • C-Reactive Protein / antagonists & inhibitors
  • C-Reactive Protein / immunology
  • C-Reactive Protein / metabolism
  • Complement C1q / antagonists & inhibitors
  • Complement C1q / immunology*
  • Complement C1q / metabolism
  • Epitopes
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Lupus Nephritis / blood
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / pathology
  • Male
  • Middle Aged
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Subunits
  • Recombinant Proteins / immunology*
  • Recombinant Proteins / metabolism
  • Severity of Illness Index

Substances

  • Autoantibodies
  • Epitopes
  • Immunoglobulin G
  • Protein Subunits
  • Recombinant Proteins
  • Complement C1q
  • C-Reactive Protein