MOLECULAR MIMICRY AS A THERAPEUTIC APPROACH FOR AN AUTOIMMUNE-DISEASE- ORAL TREATMENT OF UVEITIS-PATIENTS WITH AN MHC-PEPTIDE CROSS-REACTIVE WITH AUTOANTIGEN - FIRST RESULTS

In the rat model of experimental autoimmune uveitis (EAU) we have demo nstrated that a peptide from the sequence of human disease-associated MHC-class I antigens can induce uveitis upon immunization. Moreover, o ral administration of this MHC-peptide tolerized Lewis rats to the dis ease induced with two different retinal autoantigens, retinal S-Antige n (S-Ag) and IRBP. In uveitis patients T cells responding to S-Ag pept ide also respond to the MHC-peptide, which shows crossreactivity with the major epitope from S-Ag due to some shared discontinuous amino aci d homologies. The 14-mer peptide B27PD is derived from the sequence of all HLA-B antigens that are statistically associated with uveitis (in cluding HLA-B27). Patients with long-lasting endogenous uveitis, suffe ring from side effects of conventional immune-suppressive therapy or b eing therapy-refractive, were orally tolerized with peptide B27PD in t his first open therapeutic trial. Patients received peptide three time s a week over a 12 weeks period, while only low dose steroids were all owed as concomitant medication. The aims were (1) to investigate wheth er immunosuppressive therapy could be discontinued and steroids reduce d while relapses of ocular inflammation reside and (2) to search for s ide effects. The Helsinki Declaration was strictly observed and the st udy design approved by the local ethical committee. The first patients orally tolerized with the HLA-peptide (two had stopped azathioprine i mmediately prior to onset of oral peptide treatment) could discontinue their steroids because of reduced intraocular inflammation. No side e ffects of therapy were observed. Oral tolerance induction with a pepti de derived from the patients: own HLA-antigens and crossreactive with the organ-specific autoantigen seems to be a potent therapeutic approa ch. (C) 1997 Elsevier Science B.V.