Strong acceleration of murine lupus by injection of the SmD183-119 peptide

Gabriela Riemekasten*, Annegret Kawald, Catarina Weiß, Andrea Meine, Jeannette Marell, Rolf Klein, Berthold Hocher, Christian Meisel, Gert Hausdorf, Rudi Manz, Thomas Kamradt, G. R. Burmester, Falk Hiepe

*Corresponding author for this work
23 Citations (Scopus)


Objective. The mechanisms of IgG anti-double-stranded DNA (anti-dsDNA) antibody induction are incompletely understood. We recently demonstrated a high prevalence of autoantibodies to the C-terminus of SmD1 in patients with systemic lupus erythematosus (SLE) that was closely associated with anti-dsDNA reactivity. The aim of the present study was to analyze the influence of the SmD1 C-terminus on the generation of pathogenic anti-dsDNA antibodies in a murine model of SLE. Methods. Female lupus-prone prenephritic (NZB × NZW)F1 mice (NZB/NZW mice) as well as female control BALB/c, NZW, and (BALB/c × NZW)F1 mice (CWF1 mice) were subcutaneously injected with keyhole limpet hemocyanin (KLH)-coupled SmD1183-119. Controls received injections of recombinant SmD1 (rSmD1), KLH-rSmD1, KLH-coupled randomized peptide of SmD183-119, ovalbumin, or saline. Animals were monitored for survival and proteinuria and for levels of plasma creatinine, urea, and autoantibodies. In addition, histologic examinations were performed and T cell responses against SmD183-119 peptide and rSmD1 protein were determined in SmD183-119-treated and -untreated NZB/NZW mice. Results. Immunization with KLH-SmD183-119, but not with control peptide, significantly accelerated the natural course of lupus in NZB/NZW mice, with premature renal failure and increased development of anti-dsDNA antibodies. Control strains of mice remained healthy, with no relevant anti-SmD183-119 antibodies detectable even after immunization. In contrast to findings in control mice, a T cell response against SmD183-119 was already present in unmanipulated NZB/NZW mice, and this response was further amplified after immunization. Conclusion. The SmD183-119 peptide can influence the pathogenic anti-dsDNA response in the NZB/NZW murine lupus model. The data suggest that an SmD183-119-speciflc T cell response is critical. Therefore, modulation of these autoantigen-specific T cells by tolerance induction may provide a therapeutic approach to specific immunosuppression in lupus.

Original languageEnglish
JournalArthritis and Rheumatism
Issue number10
Pages (from-to)2435-2445
Number of pages11
Publication statusPublished - 2001

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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