Oral tolerance with an HLA-peptide mimicking retinal autoantigen as a treatment of autoimmune uveitis

Endogenous uveitis is a T cell mediated autoimmune disease leading to impai rment of visual acuity. The association of different uveitis entities with HLA-class I antigens and the discovery of antigenic mimicry between a pepti de of uveitis-associated HLA-class I antigens and a peptide of retinal auto antigen led to a new hypothesis for the pathogenesis of uveitis. On the bas is of this mechanism an open trial of oral tolerance induction with the HLA -peptide B27PD was initiated for nine patients with long lasting, therapy-r efractive uveitis. Within 6 weeks of oral peptide treatment all patients re sponded with a marked decrease of intraocular inflammation, which allowed a reduction of systemic corticosteroids in seven patients. One patient, who suffered from an acute relapse, responded within 2 weeks, followed by an in crease of visual acuity. In addition, two patients discontinued azathioprin e immediately prior to oral tolerance induction without the occurrence of r elapses. Visual acuity remained unchanged or increased in 14 of 16 eyes. On e patient did not finish oral peptide treatment. None of these patients exp erienced any adverse events. It was concluded that the oral application of highly tolerogenic peptides might be a potent approach for the treatment of autoimmune diseases. (C) 1999 Elsevier Science B.V. All rights reserved.