Association of anti-nucleoprotein autoantibodies with upregulation of Type I interferon-inducible gene transcripts and dendritic cell maturation in systemic lupus erythematosus

Clin Immunol. 2005 Dec;117(3):238-50. doi: 10.1016/j.clim.2005.07.009. Epub 2005 Aug 25.


Lupus patients selectively produce autoantibodies against nucleoproteins. Since the RNA/DNA components of these autoantigens are endogenous TLR ligands capable of stimulating Type I interferon (IFN-I) production, we asked whether autoantibodies against the ribonucleoproteins Sm/RNP and Ro60 and double-stranded DNA are associated with high levels of IFN-I. IFN-I levels were increased in SLE (n = 88) vs. other autoimmune diseases (n = 82) and controls (n = 57) (P < 0.0001) and were associated positively with autoantibodies against Sm/RNP, Ro60/La, and dsDNA but negatively with anti-phospholipid. Low numbers of circulating plasmacytoid and myeloid dendritic cells also were associated with these autoantibodies. The IFN-I and dendritic cell abnormalities correlated with disease severity and were not therapy-related. These findings suggest that immunostimulatory nucleic acid components of autoantigens may act as endogenous adjuvants by promoting IFN-I production and dendritic cell maturation, helping to explain the high prevalence of autoantibodies against nucleoprotein antigens in SLE.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Antinuclear / immunology*
  • Autoantigens / immunology
  • Cell Differentiation / immunology
  • DNA / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Female
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • Humans
  • Interferon Type I / biosynthesis*
  • Interferon-alpha / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / pathology
  • Male
  • Myxovirus Resistance Proteins
  • RNA, Small Cytoplasmic / immunology
  • Ribonucleoproteins / immunology*
  • Severity of Illness Index
  • Up-Regulation


  • Antibodies, Antinuclear
  • Autoantigens
  • Interferon Type I
  • Interferon-alpha
  • Myxovirus Resistance Proteins
  • RNA, Small Cytoplasmic
  • RO60 protein, human
  • Ribonucleoproteins
  • DNA
  • GTP-Binding Proteins