Systematic identification of novel SLE related autoantibodies responsible for type I IFN production in human plasmacytoid dendritic cells

Cell Immunol. 2013 Jul-Aug;284(1-2):119-28. doi: 10.1016/j.cellimm.2013.07.017. Epub 2013 Aug 6.

Abstract

Plasmacytoid dendritic cells [pDC], also known as type I interferon [IFN] producing cells, play a significant role in the pathogenesis of systemic lupus erythematosus [SLE]. The current study was undertaken to identify novel SLE autoantibody specificities associated with interferon-inducing activity in human pDCs. We found that immune complex mixtures from some Interferon signature negative [IFN-] and all interferon signature positive [IFN+] SLE patients could trigger type I IFN production by pDCs. IgGs from IFN- and IFN+ SLE patients were subsequently screened via a high throughput protein microarray to identify novel auto-antibody specifities that mediate type I IFN production by pDCs. This approach identified five novel autoantibodies that may contribute to type I IFN production by pDCs via a nucleic acid dependent mechanism. The newly identified autoantibody specificities function in a myriad of cell processess and, to date, have not been implicated in SLE pathogenesis.

Keywords: Autoimmune; Innate immunity; Plasmacytoid dendritic cells; Protein array; SLE; Type I interferons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Antibody Complex / immunology*
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Cell Line
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Interferon-alpha / biosynthesis*
  • Interferon-alpha / immunology*
  • Leukocytes, Mononuclear / immunology
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Protein Array Analysis

Substances

  • Antigen-Antibody Complex
  • Autoantibodies
  • Interferon-alpha