Thurau S R, Diedrichs-Möhring M, Fricke H, Burchardi C, Wildner G
University Eye Hospital, Section of Immunobiology, Ludwig-Maximilians-University, Munich, Germany.
Immunol Lett. 1999 Jun 1;68(2-3):205-12. doi: 10.1016/s0165-2478(99)00071-1.
Endogenous uveitis is a T cell mediated autoimmune disease leading to impairment of visual acuity. The association of different uveitis entities with HLA-class I antigens and the discovery of antigenic mimicry between a peptide of uveitis-associated HLA-class I antigens and a peptide of retinal autoantigen led to a new hypothesis for the pathogenesis of uveitis. On the basis of this mechanism an open trial of oral tolerance induction with the HLA-peptide B27PD was initiated for nine patients with long lasting, therapy-refractive uveitis. Within 6 weeks of oral peptide treatment all patients responded 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 increase of visual acuity. In addition, two patients discontinued azathioprine immediately prior to oral tolerance induction without the occurrence of relapses. Visual acuity remained unchanged or increased in 14 of 16 eyes. One patient did not finish oral peptide treatment. None of these patients experienced 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.
内源性葡萄膜炎是一种由T细胞介导的自身免疫性疾病，可导致视力受损。不同葡萄膜炎实体与HLA - I类抗原的关联以及葡萄膜炎相关HLA - I类抗原的一种肽段与视网膜自身抗原的一种肽段之间抗原模拟的发现，引发了关于葡萄膜炎发病机制的新假说。基于这一机制，对9例患有长期难治性葡萄膜炎的患者开展了一项使用HLA肽B27PD诱导口服耐受的开放性试验。在口服肽治疗的6周内，所有患者的眼内炎症均显著减轻，7例患者得以减少全身皮质类固醇的用量。1例急性复发的患者在2周内有反应，随后视力提高。此外，2例患者在诱导口服耐受前立即停用硫唑嘌呤，未出现复发。16只眼中有14只眼的视力保持不变或提高。1例患者未完成口服肽治疗。这些患者均未出现任何不良事件。得出的结论是，口服高耐受性肽可能是治疗自身免疫性疾病的有效方法。
