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 language | English (US) |
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Pages (from-to) | 865-871 |
Number of pages | 7 |
Journal | Lupus |
Volume | 11 |
Issue number | 12 |
DOIs | |
State | Published - 2002 |
Keywords
- Lupus nephritis
- Peptide mimetopes
- Phage libraries
- SLE
- α-actinin
ASJC Scopus subject areas
- Rheumatology