Antigenic triggers and molecular targets for anti-double-stranded DNA antibodies

B. Deocharan, X. Qing, E. Beger, C. Putterman

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

While anti-double-stranded (ds)DNA antibodies are a characteristic serologic hallmark for SLE, the triggering antigen is unknown. Using phage display libraries, we identified DWEYSVWLSN as a peptide mimic of DNA for a pathogenic anti-dsDNA antibody. Peptide immunization of non-autoimmune mice induced anti-dsDNA as well as other lupus-associated antibodies. Molecular analysis of the induced anti-dsDNA antibodies revealed several similarities with anti-dsDNA antibodies that appear spontaneously in lupus mice. Furthermore, lupus-prone mice immunized with this peptide DNA mimic had higher autoantibody titers as well as more severe nephritis. Anti-DNA antibodies may contribute to lupus nephritis via cross-reactivity with renal antigen. Using western blotting of lysates of mesangial cells from a lupus mouse, we found that a pathogenic anti-DNA antibody binds to α-actinin. High titers of anti-α-actinin antibodies were present in the sera and kidney eluates of lupus mice with active disease. Binding to α-actinin was diminished in mesangial cells derived from BALB/c mice, suggesting that target antigen expression may play a role in determining autoantibody binding to the kidney. We conclude that a pathogenic, lupus-like autoantibody response can be induced by a peptide antigen, and that α-actinin is a cross-reactive renal target for the pathogenic anti-dsDNA autoantibody response in lupus mice.

Original languageEnglish (US)
Pages (from-to)865-871
Number of pages7
JournalLupus
Volume11
Issue number12
DOIs
StatePublished - Dec 1 2002

Keywords

  • Lupus nephritis
  • Peptide mimetopes
  • Phage libraries
  • SLE
  • α-actinin

ASJC Scopus subject areas

  • Rheumatology

Fingerprint Dive into the research topics of 'Antigenic triggers and molecular targets for anti-double-stranded DNA antibodies'. Together they form a unique fingerprint.

  • Cite this