A Peptide DNA Surrogate Accelerates Autoimmune Manifestations and Nephritis in Lupus-Prone Mice

• Published in: The Journal of immunology (1950) Vol. 168; no. 7; pp. 3617 - 3626
• Main Authors: Beger, Erik, Deocharan, Bisram, Edelman, Morris, Erblich, Bryna, Gu, Yun, Putterman, Chaim
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.04.2002
• Subjects: Animals; anti-DNA antibodies; Antibodies, Antinuclear - biosynthesis; Antibodies, Antinuclear - metabolism; Clone Cells; Cross Reactions; DNA - immunology; Female; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Gene Rearrangement, B-Lymphocyte, Light Chain; Genetic Predisposition to Disease; Immunoglobulin kappa-Chains - genetics; Immunoglobulin Variable Region - genetics; Injections, Subcutaneous; Lupus Nephritis - genetics; Lupus Nephritis - immunology; Lupus Nephritis - pathology; Mice; Mice, Inbred NZB; Molecular Mimicry - genetics; Molecular Mimicry - immunology; Molecular Sequence Data; Oligopeptides - administration & dosage; Oligopeptides - immunology; Oligopeptides - metabolism; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.7.3617

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 x NZW)F(1) 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 x NZW)F(1) 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.