HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The mechanism by which a peptide based on complementarity-determining region-1 of a pathogenic anti-DNA auto-Ab ameliorates experimental systemic lupus erythematosus.

Abstract
A peptide based on complementarity-determining region (CDR)-1 of a monoclonal murine anti-DNA Ab that bears the common idiotype, 16/6Id, was synthesized and characterized. The peptide, designated pCDR1, was found to be an immunodominant T-cell epitope in BALB/c mice. The CDR1-based peptide was shown to be capable of inhibiting the in vivo priming of BALB/c mice immunized with the peptide or with the whole anti-DNA 16/6Id(+) mAbs of either mouse or human origin. We show here that administration of pCDR1 (weekly, i.v., 100 microgram/mouse) in aqueous solution for 5 weeks starting at the time of disease induction with the human 16/6Id prevented the development of clinical manifestations of experimental systemic lupus erythematosus (SLE). Further, 10 weekly injections of pCDR1 to BALB/c mice with an established experimental SLE down-regulated clinical manifestations of SLE (e.g., anti-DNA auto-Abs, leukopenia, proteinuria, immune complex deposits in the kidneys) in the treated mice. Prevention of SLE induction was shown to be associated mainly with a decrease in the levels of IL-2, INFgamma, and the proinflammatory cytokine TNFalpha. On the other hand, the secretion of the immunosuppressive cytokine TGFbeta was elevated. Amelioration of the clinical manifestations of an already established experimental SLE correlated with a dramatic decrease in TNFalpha secretion, elevated levels of TGFbeta, and immunomodulation of the Th1 and Th2 type cytokines to levels close to those observed in healthy mice.
AuthorsE Eilat, M Dayan, H Zinger, E Mozes
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 98 Issue 3 Pg. 1148-53 (Jan 30 2001) ISSN: 0027-8424 [Print] United States
PMID11158609 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Cytokines
  • Epitopes
  • Immunoglobulin Fragments
Topics
  • Amino Acid Sequence
  • Animals
  • Antibodies, Antinuclear (blood, chemistry, immunology)
  • Antibodies, Monoclonal (chemistry, immunology)
  • Cells, Cultured
  • Cytokines (biosynthesis)
  • Disease Models, Animal
  • Drug Administration Schedule
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes (immunology)
  • Humans
  • Immunoglobulin Fragments (administration & dosage, chemistry, therapeutic use)
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Lupus Erythematosus, Systemic (immunology, pathology, prevention & control)
  • Lymphocytes (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Spleen (immunology)
  • T-Lymphocytes (immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: