Molecular mimicry as a therapeutic approach for an autoimmune disease: oral treatment of uveitis-patients with an MHC-peptide crossreactive with autoantigen--first results.

In the rat model of experimental autoimmune uveitis (EAU) we have demonstrated that a peptide from the sequence of human disease-associated MHC-class I antigens can induce uveitis upon immunization. Moreover, oral administration of this MHC-peptide tolerized Lewis rats to the disease induced with two different retinal autoantigens, retinal S-antigen (S-Ag) and IRBP. In uveitis patients T cells responding to S-Ag peptide also respond to the MHC-peptide, which shows crossreactivity with the major epitope from S-Ag due to some shared discontinuous amino acid homologies. The 14-mer peptide B27PD is derived from the sequence of all HLA-B antigens that are statistically associated with uveitis (including HLA-B27). Patients with long-lasting endogenous uveitis, suffering from side effects of conventional immuno-suppressive therapy or being therapy-refractive, were orally tolerized with peptide B27PD in this first open therapeutic trial. Patients received peptide three times a week over a 12 weeks period, while only low dose steroids were allowed as concomitant medication. The aims were (1) to investigate whether immunosuppressive therapy could be discontinued and steroids reduced while relapses of ocular inflammation reside and (2) to search for side effects. The Helsinki Declaration was strictly observed and the study design approved by the local ethical committee. The first patients orally tolerized with the HLA-peptide (two had stopped azathioprine immediately prior to onset of oral peptide treatment) could discontinue their steroids because of reduced intraocular inflammation. No side effects of therapy were observed. Oral tolerance induction with a peptide derived from the patients' own HLA-antigens and crossreactive with the organ-specific autoantigen seems to be a potent therapeutic approach.