TY - JOUR
T1 - Treatment of lupus patients with a tolerogenic peptide, hCDR1 (Edratide)
T2 - Immunomodulation of gene expression
AU - Sthoeger, Zev M.
AU - Sharabi, Amir
AU - Molad, Yair
AU - Asher, Ilan
AU - Zinger, Heidy
AU - Dayan, Molly
AU - Mozes, Edna
PY - 2009/8
Y1 - 2009/8
N2 - 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-β, 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-1β, TNF-α, IFN-γ, 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-β 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.
AB - 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-β, 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-1β, TNF-α, IFN-γ, 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-β 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.
KW - Immunomodulation of gene expression
KW - Lupus patients
KW - Peptide-based treatment
KW - Systemic lupus erythematosus
KW - Tolerogenic peptide
UR - http://www.scopus.com/inward/record.url?scp=67349261724&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2009.03.009
DO - 10.1016/j.jaut.2009.03.009
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C2 - 19346102
AN - SCOPUS:67349261724
SN - 0896-8411
VL - 33
SP - 77
EP - 82
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
IS - 1
ER -