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分子识别理论与反义相互作用:在自身免疫中的治疗应用

Molecular recognition theory and sense-antisense interaction: therapeutic applications in autoimmunity.

作者信息

Hardison Matthew Thomas, Blalock James Edwin

机构信息

Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham 1918 University Blvd, Birmingham, AL 35294, USA.

出版信息

Front Biosci (Elite Ed). 2012 Jan 1;4(5):1864-70. doi: 10.2741/e508.

Abstract

Perhaps behind only the understanding of the genetic code in importance is the comprehension of protein sequence and structure in its effect on modern scientific investigation. How proteins are structured and interact dictates a considerable amount of the body's processes in maintaining homeostasis. Unfortunately, in diseases of autoimmunity, these processes are directed against the body itself and most of the current clinical responses are severely lacking. This review addresses current therapeutics involved in the treatment of various autoimmune diseases and details potential future therapeutics designed with a more targeted approach. Detailed in this manuscript is the concept of utilizing peptides possessing an inverse hydropathy to the immunogenic region of proteins to generate anti-idiotypic (anti-Id) and anti-clonotypic T cell receptor (TCR) antibodies (Abs). Theoretically, the anti-Id Abs cross react with Id Abs and negate the powerful machinery of the adaptive immune response with little to no side effects. A series of studies by a number of groups have shown this to be an exciting and intriguing concept that will likely play a role in the future treatment of autoimmune diseases.

摘要

在重要性方面,或许仅次于对遗传密码的理解的是对蛋白质序列和结构在现代科学研究中的影响的理解。蛋白质的结构和相互作用方式在很大程度上决定了身体维持内环境稳定的过程。不幸的是,在自身免疫性疾病中,这些过程针对的是身体自身,而目前大多数临床应对措施严重不足。本综述探讨了当前用于治疗各种自身免疫性疾病的疗法,并详细介绍了未来设计的更具针对性的潜在疗法。本手稿详细阐述了利用与蛋白质免疫原性区域具有相反亲水性的肽来产生抗独特型(抗Id)和抗克隆型T细胞受体(TCR)抗体(Abs)的概念。从理论上讲,抗Id抗体与Id抗体发生交叉反应,并以几乎没有副作用的方式抵消适应性免疫反应的强大机制。多个研究小组进行的一系列研究表明,这是一个令人兴奋且引人入胜的概念,很可能在未来自身免疫性疾病的治疗中发挥作用。

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本文引用的文献

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The neuropathological basis of clinical progression in multiple sclerosis.多发性硬化症临床进展的神经病理学基础。
Acta Neuropathol. 2011 Aug;122(2):155-70. doi: 10.1007/s00401-011-0840-0. Epub 2011 May 28.
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Cochrane Database Syst Rev. 2011 Feb 16(2):CD006986. doi: 10.1002/14651858.CD006986.pub2.
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Therapy of MS.多发性硬化症的治疗
Clin Neurol Neurosurg. 2010 Jun;112(5):365-85. doi: 10.1016/j.clineuro.2010.03.010. Epub 2010 Apr 1.

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