A new model of induced experimental systemic lupus erythematosus (SLE) in pigs and its amelioration by treatment with a tolerogenic peptide

Amir Sharabi, Molly Dayan, Heidy Zinger, Edna Mozes

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Systemic lupus erythematosus (SLE) is characterized by a variety of autoantibodies and systemic clinical manifestations. A tolerogenic peptide, hCDR1, ameliorated lupus manifestations in mice models. The objectives of this study were to induce experimental SLE in pigs and to determine the ability of hCDR1 to immunomodulate the disease manifestations. Results and Discussion: We report here the successful induction, by a monoclonal anti-DNA antibody, of an SLE-like disease in pigs, manifested by autoantibody production and glomerular immune complex deposits. Treatment of pigs with hCDR1 ameliorated the lupus-related manifestations. Furthermore, the treatment downregulated the gene expression of the pathogenic cytokines, interleukin (IL)-1β, tumor necrosis factor alpha, interferon gamma, and IL-10, and upregulated the expression of the immunosuppressive cytokine transforming growth factor beta, the antiapoptotic molecule Bcl-xL, and the suppressive master gene, Foxp3, hence restoring the expression of the latter to normal levels. Thus, hCDR1 is capable of ameliorating lupus in large animals and is a potential candidate for the treatment of SLE patients.

Original languageEnglish
Pages (from-to)34-44
Number of pages11
JournalJournal of Clinical Immunology
Volume30
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Keywords

  • Experimental SLE in pigs
  • Glomerular immune complex deposits
  • Immunomodulation of gene expression
  • Peptide therapy

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