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如何智胜大自然——自身免疫:从阴影走向阳光。

How to outfox mother nature--autoimmunity: moving from shadows to sunshine.

作者信息

Borchers A T, Keen C L, Shoenfeld Y, Gershwin M E

机构信息

Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, USA.

出版信息

Isr Med Assoc J. 2000 Jul;2 Suppl:15-22.

Abstract

The morbidity and disability associated with autoimmune diseases represent a significant health problem. One in 31 people have one form or another of an autoimmune disease. Despite the avalanche of molecular data, immunogenetic definitions and improvements in serologic diagnosis, we are still far from discovering the etiologies of these diseases. For some autoimmune diseases, there may be a very long latency period between disease onset and clinical presentation. Existing therapies tend to be only partially successful and often accompanied by a variety of serious side effects. However, even in the absence of a complete understanding of the underlying genetic, environmental and coincidental factors that confer susceptibility to autoimmune diseases, we believe that it is possible to devise successful therapies by interfering with one or more of the pathways of destruction characteristic of a specific autoimmune disease. We have prepared a futuristic look at the treatment of autoimmune disease by extrapolation of current research directions as well as thoughts on new methods of delivery of recombinant monoclonal antibodies. We predict that we will "cure" autoimmune pathology long before we understand the etiology. In the case of inflammatory bowel disease, as a model, and taking advantage of what is known on animal studies, we illustrate the progress that has been made in elucidating these pathways of destruction and speculate about possible therapeutic approaches.

摘要

自身免疫性疾病所带来的发病率和残疾问题是一个重大的健康难题。每31人中就有1人患有某种形式的自身免疫性疾病。尽管有大量的分子数据、免疫遗传学定义以及血清学诊断方面的改进,但我们距离发现这些疾病的病因仍相差甚远。对于某些自身免疫性疾病,从疾病发作到临床表现可能存在很长的潜伏期。现有的治疗方法往往仅取得部分成功,并且常常伴随着各种严重的副作用。然而,即使在尚未完全了解导致自身免疫性疾病易感性的潜在遗传、环境和偶发因素的情况下,我们相信通过干扰特定自身免疫性疾病特有的一种或多种破坏途径,有可能设计出成功的治疗方法。我们通过推断当前的研究方向以及对重组单克隆抗体新递送方法的思考,对自身免疫性疾病的治疗进行了前瞻性展望。我们预测,在理解病因之前很久,我们就能“治愈”自身免疫性病理。以炎症性肠病为例,利用动物研究中已知的信息,我们阐述了在阐明这些破坏途径方面取得的进展,并推测了可能的治疗方法。

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