A peptide DNA surrogate accelerates autoimmune manifestations and nephritis in lupus-prone mice

Erik Beger, Bisram Deocharan, Morris Edelman, Bryna Erblich, Yun Gu, Chaim Putterman

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Lupus-associated anti-DNA Abs display features of Ag selection, yet the triggering Ag in the disease is unknown. We previously demonstrated that the peptide DWEYSVWLSN is bound by a pathogenic anti-DNA Ab, and that immunization of nonautoimmune mice with this peptide induces autoantibodies and renal Ig deposition. To elucidate differences in the induced B cell responses in mice genetically predisposed to autoimmunity, young (NZB × NZW)F1 mice were immunized with this peptide DNA mimetope. DWEYSVWLSN-immunized mice had significantly increased IgG anti-dsDNA, anti-laminin, and anti-cardiolipin Ab titers compared with controls. In addition, glomerular histopathology in the form of endocapillary disease and crescent formation was markedly more severe in DWEYSVWLSN-immunized mice. Analysis of mAbs from DWEYSVWLSN-immunized mice revealed that anti-peptide Abs were often cross-reactive with DNA. Genetic elements used in the Ab response in immunized mice were homologous to those used in the spontaneous anti-DNA response in (NZB × NZW)F1 mice, as well as in other, experimentally induced anti-DNA Abs. Our results indicate that peptide immunization can induce a molecular genetic response common to a variety of stimuli that break tolerance to mammalian dsDNA. Based on the similarity between spontaneously arising anti-DNA Abs and several types of induced anti-DNA Abs, we suggest that there may be more than a single Ag that can trigger systemic lupus erythematosus.

Original languageEnglish
Pages (from-to)3617-3626
Number of pages10
JournalJournal of Immunology
Issue number7
StatePublished - 1 Apr 2002
Externally publishedYes


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