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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Erik BegerChaim Putterman

Abstract

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 toler...Continue Reading

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Citations

Mar 17, 2018·Frontiers in Immunology·Ole Petter Rekvig
Dec 4, 2019·Arthritis Research & Therapy·Huixia WangYumin Xia
Aug 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chaim O JacobWilliam Stohl
Nov 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zeguo ZhaoChaim Putterman
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amanda M GuthLawrence J Wysocki
Oct 21, 2015·Clinical and Experimental Immunology·Y XiaC Putterman
Mar 5, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·T Matt HollGarnett Kelsoe
Jan 22, 2004·Clinica Chimica Acta; International Journal of Clinical Chemistry·John G RoutsiasHaralampos M Moutsopoulos

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