Oral administration of different forms of a tolerogenic peptide to define the preparations and doses that delay anti-DNA antibody production and nephritis and prolong survival in SLE-prone mice.

摘要

Therapeutic agents currently in use to treat systemic lupus erythematosus (SLE) are predominantly immunosuppressive agents with limited specificities. Multiple groups, including ours, have illustrated that inducing tolerance in SLE animal models ameliorates disease symptoms and increases survival. We examined if oral administration of a tolerogenic peptide could affect SLE disease progression. The pConsensus (pCons) peptide, based on protein sequences of anti-double stranded (anti-ds)DNA antibodies, induces tolerance through upregulation of regulatory T cells when administered intravenously. Six different forms of pCons, including multiple antigenic peptides (MAP) and cyclic peptides made up of L- and D-amino acids, at three different concentrations, were fed to BWF1 SLE-susceptible mice for 30 weeks. Mice fed 100 microg of L-MAP or D-MAP had less cumulative proteinuria and serum anti-dsDNA antibody levels than controls. In addition, animals in these groups also survived significantly longer than controls with a corresponding increase in serum transforming growth factor beta (TGFbeta, implying a protective role for pCons-induced regulatory T cells. Oral administration of a tolerogenic peptide is a safe, effective method for ameliorating SLE disease manifestations and prolonging survival in SLE-prone mice. Induction of oral tolerance using modified pCons peptides could lead to a novel targeted therapy for human SLE.