Interactions between autoimmunity and molecular and cell biology. Bridges between clinical and basic sciences.

Interactions between autoimmunity and molecular and cell biology. Bridges between clinical and basic sciences.
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自身免疫与分子和细胞生物学之间的相互作用。

DOI:
10.1172/jci114127
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发表时间:
1989
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Tan,EM
Tan,EM
中科院分区:
--
文献类型:
--
作者:
Tan,EM

文献摘要

被引文献

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一组系统性自身免疫性疾病,包括系统性红斑狼疮 (SLE)、硬皮病、干燥综合征、皮肌炎/多发性肌炎和混合结缔组织病 (MCTD),其特征是独特的免疫反应,表现为自发产生与细胞内蛋白质和核酸反应的自身抗体(参考文献 1 中综述)。对临床医学产生重要影响的一项发现证明,上述每种疾病都有其各自的一组自身抗体,因此自身抗体谱可用于鉴别诊断。在分子和细胞生物学中,自身抗体已被用来阐明细胞内分子的分子结构及其在重要细胞内过程的生物学功能中的作用。该研究领域的临床和基础科学之间的相互作用在过去十年中特别活跃,是在这些学科之间建立桥梁的一个很好的例子。大多数早期关于自身抗体的研究都集中在与 DNA 和核蛋白反应的抗体上,后者现在被认为是脱氧核糖核蛋白的组蛋白成分。这些研究证明了 DNA 自身抗体通过免疫复合物形成在组织炎症发病机制中的重要作用 (2, 3),并激发了对自身抗体与疾病机制关系的持续研究。 1966 年,通过琼脂糖凝胶双扩散分析中的免疫沉淀定义了一种称为 Sm 的非组蛋白核蛋白抗原 (4)。 Sm 抗原被证明是一种位于核内的蛋白质,并且发现抗体对 SLE 具有高度特异性。此后不久,狼疮和 MCTD 患者血清中存在的抗体鉴定出另一种核抗原,并且由于免疫学研究表明 RNA 和 MCTD 的完整性
A group of systemic autoimmune diseases, including systemic lupus erythematosus (SLE),'scleroderma, Sjogren's syn-drome, dermatomyositis/polymyositis, and mixed connective tissue disease (MCTD), are characterized by a distinctive im-mune response which is manifested as the spontaneous pro-duction ofautoantibodies that react with intracellular proteins and nucleic acids (reviewed in reference 1). A finding thathas had an important impact on clinical medicine has been the demonstration that each ofthe diseases described above has its own individual set of autoantibodies, so that autoantibody profiles havebeen useful in differential diagnosis. In molecular and cell biology, autoantibodies have been used to clarify the molecular structure ofintracellular molecules and their role in the biological function of important intracellular processes. The interactions between clinical and basic sciences in this field of research have been especially active in the past decade and are a good example of bridges being built between these disciplines.Most of the earlier studies on autoantibodiesfocused on those reactive with DNA and nucleoproteins, the latter now recognized as the histone components ofdeoxyribonucleoprotein. These studies demonstrated the important role of au-toantibody to DNA in the pathogenesis of tissue inflammation via immune complex formation (2, 3) and stimulated continued investigations into the relationship of autoantibodies with disease mechanisms. A nonhistone nuclear protein antigen called Sm was defined in 1966 by immunoprecipitation in agarose gel double diffusion analysis (4). The Sm antigen was shown to be a protein that was nuclear in location and anti-bodies were found to behighly specific for SLE. Shortly there-after, another nuclear antigen was identified with antibodies present in sera of patients with lupus and MCTD, and since immunological studies showed that integrity ofboth RNA and