Choy E H
Department of Rheumatology, Guy's, King's and St Thomas' Hospitals School of Medicine, King's College Hospital, East Dulwich Grove, London, SE22 8PT, UK.
Curr Opin Investig Drugs. 2000 Sep;1(1):58-62.
Rheumatoid arthritis (RA) is a common inflammatory and destructive arthropathy. Its precise pathogenesis remains unknown but there is evidence to suggest it is an autoimmune disease. Recently, a number of candidate autoantigens have been identified in RA. Modulating the immune response to the autoantigens by oral tolerance may lead to safer and more effective treatment. Oral tolerance is a state of systemic immune suppression to an antigen induced by oral feeding of the same antigen. In animal models, oral feeding with pathogenic antigens prevents and reduces the severity of autoimmune diseases. Even in diseases where the pathogenic autoantigens are unknown, bystander suppression can be induced using antigens present in the anatomical vicinity. Hence, oral tolerance has been advocated as a treatment strategy for autoimmune diseases including RA. Clinical trials of chicken and bovine type II collagen, a major constituent of articular cartilage, produced conflicting results in RA. This review examines the scientific basis of oral tolerance, discusses the apparent discrepancy in clinical trial results and looks at the future prospect.
类风湿性关节炎(RA)是一种常见的炎症性破坏性关节病。其确切发病机制尚不清楚,但有证据表明它是一种自身免疫性疾病。最近,在类风湿性关节炎中已鉴定出许多候选自身抗原。通过口服耐受调节对自身抗原的免疫反应可能会带来更安全、更有效的治疗方法。口服耐受是通过口服相同抗原诱导产生的对该抗原的全身性免疫抑制状态。在动物模型中,口服致病性抗原可预防和减轻自身免疫性疾病的严重程度。即使在致病性自身抗原未知的疾病中,也可使用解剖学邻近部位存在的抗原诱导旁观者抑制。因此,口服耐受已被倡导作为包括类风湿性关节炎在内的自身免疫性疾病的一种治疗策略。对关节软骨的主要成分鸡和牛II型胶原蛋白进行的临床试验在类风湿性关节炎中产生了相互矛盾的结果。本综述探讨了口服耐受的科学依据,讨论了临床试验结果中明显的差异,并展望了未来前景。