Amelioration of SLE-like manifestations in (NZBxNZW)F1 mice following treatment with a peptide based on the complementarity determining region 1 of an autoantibody is associated with a down-regulation of apoptosis and of the pro-apoptotic factor JNK kinase

Clin Immunol. 2005 Dec;117(3):262-70. doi: 10.1016/j.clim.2005.09.003. Epub 2005 Oct 27.


Treatment with peptides based on the complementarity determining regions (CDR) of murine and human monoclonal anti-DNA antibodies that bear the common idiotype, 16/6 Id, ameliorates disease manifestations of mice with either induced or spontaneous SLE. Aberrant expression and function of the p21Ras/MAP kinase pathway are associated with active SLE. Therefore, we examined the effect of treatment with a CDR1-based peptide of a human autoantibody (hCDR1) on the p21Ras pathway and SLE manifestations of SLE-prone (NZBxNZW)F1 mice. Untreated SLE-afflicted mice demonstrated increased expression of p21Ras and the phosphorylated active form of its down-stream element JNK kinase in conjunction with reduced hSOS and unchanged p120GAP, as compared to healthy controls. Amelioration of SLE manifestations following treatment with hCDR1 was associated with a diminished expression of phosphorylated JNK kinase, mainly in the T cell population that also exhibited reduced rates of apoptosis. Thus, hCDR1 therapy ameliorates SLE, at least in part, via down-regulation of the activity of the pro-apoptotic JNK kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Autoantibodies / drug effects*
  • Autoantibodies / immunology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Complementarity Determining Regions / therapeutic use*
  • Crosses, Genetic
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Immunization
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • MAP Kinase Kinase 4 / metabolism*
  • Mice
  • Mice, Inbred NZB
  • Peptide Fragments / therapeutic use*
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology


  • Autoantibodies
  • Complementarity Determining Regions
  • Peptide Fragments
  • MAP Kinase Kinase 4
  • Proto-Oncogene Proteins p21(ras)