Treatment of lupus patients with a tolerogenic peptide, hCDR1 (Edratide): immunomodulation of gene expression

J Autoimmun. 2009 Aug;33(1):77-82. doi: 10.1016/j.jaut.2009.03.009. Epub 2009 Apr 5.


Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by dysregulation of cytokines, apoptosis, and B- and T-cell functions. The tolerogenic peptide, hCDR1 (Edratide), ameliorated the clinical manifestations of murine lupus via down-regulation of pro-inflammatory cytokines and apoptosis, up-regulation of the immunosuppressive cytokine TGF-beta, and the induction of regulatory T-cells. In the present study, gene expression was determined in peripheral blood mononuclear cells of 9 lupus patients that were treated for 26 weeks with either hCDR1 (five patients), or placebo (four patients). Disease activity was assessed by SLEDAI-2K and the BILAG scores. Treatment with hCDR1 significantly down-regulated the mRNA expression of the pathogenic cytokines IL-1beta, TNF-alpha, IFN-gamma, and IL-10, of BLyS (B-lymphocyte stimulator) and of the pro-apoptotic molecules caspase-3 and caspase-8. In contrast, the treatment up-regulated in vivo gene expression of both TGF-beta and FoxP3. Furthermore, hCDR1 treatment resulted in a significant decrease in SLEDAI-2K (from 8.0+/-2.45 to 4.4+/-1.67; P=0.02) and BILAG (from 8.2+/-2.7 to 3.6+/-2.9; P=0.03) scores. Thus, the tolerogenic peptide hCDR1, immunomodulates, in vivo, the expression of genes that play a role in SLE, consequently restoring the global immune dysregulation of lupus patients. Hence, hCDR1 has a potential role as a novel disease-specific treatment for lupus patients.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / administration & dosage*
  • Apoptosis / drug effects
  • Caspases / genetics
  • Caspases / immunology
  • Caspases / metabolism
  • Complementarity Determining Regions / immunology
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation / immunology
  • Humans
  • Immunotherapy*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / pathology
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / physiopathology
  • Lupus Erythematosus, Systemic / therapy
  • Male
  • Middle Aged
  • Peptide Fragments / administration & dosage*
  • Self Tolerance / immunology
  • Severity of Illness Index
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Complementarity Determining Regions
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Peptide Fragments
  • Transforming Growth Factor beta
  • edratide
  • Caspases