Open AccessThe mechanism by which a peptide based on complementarity-determining region-1 of a pathogenic anti-DNA auto-Ab ameliorates experimental systemic lupus erythematosus
Author(s) -
Eran Eilat,
Molly Dayan,
Heidy Zinger,
Edna Mozes
Publication year - 2001
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.98.3.1148
Subject(s) - immunology , idiotype , proinflammatory cytokine , cytokine , epitope , immune system , peptide , immunogenicity , tumor necrosis factor alpha , systemic lupus erythematosus , antibody , medicine , biology , monoclonal antibody , inflammation , disease , biochemistry
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 thein 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 μg/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, INFγ, and the proinflammatory cytokine TNFα. On the other hand, the secretion of the immunosuppressive cytokine TGFβ was elevated. Amelioration of the clinical manifestations of an already established experimental SLE correlated with a dramatic decrease in TNFα secretion, elevated levels of TGFβ, and immunomodulation of the Th1 and Th2 type cytokines to levels close to those observed in healthy mice.