@article{6411f2e4bad746c08e7155523f70a897,
title = "Antigenic triggers and molecular targets for anti-double-stranded DNA antibodies",
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.",
keywords = "Lupus nephritis, Peptide mimetopes, Phage libraries, SLE, α-actinin",
author = "B. Deocharan and X. Qing and E. Beger and C. Putterman",
year = "2002",
doi = "10.1191/0961203302lu308rr",
language = "אנגלית",
volume = "11",
pages = "865--871",
journal = "Lupus",
issn = "0961-2033",
publisher = "SAGE Publications Ltd",
number = "12",
}