Autoantibodies to the constitutive 73-kD member of the hsp70 family of heat shock proteins in systemic lupus erythematosus.
Autoantibodies to the constitutive 73-kD member of the hsp70 family of heat shock proteins in systemic lupus erythematosus.
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系统性红斑狼疮热休克蛋白 hsp70 家族 73-kD 组成型成员的自身抗体。
DOI：
10.1084/jem.168.4.1475
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Winfield,JB
中科院分区：
文献类型：
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作者：
Minota,S;Cameron,B;Welch,WJ;Winfield,JB
系统性红斑狼疮（SLE）的特点是发展和持久的多种自身抗体的自我成分。检测患者血清中某些自身抗体的存在具有相当大的诊断实用性，例如抗dsDNA和Smith抗原Sm（1）的抗体。SLE中的自身抗体也可用作探针，以确定其靶抗原在正常生物过程中的功能。例如，观察到U1核糖核蛋白的自身抗体在体外抑制mRNA剪接（2），这提供了一些最早的证据，表明U1核糖核蛋白对于mRNA前体的剪接是必需的。hsp70家族（3，4）由五种不同的但结构和免疫学相关的蛋白质组成：（a）组成型73-kD/pI 5.5蛋白质;（B）应激诱导型72-kD/pI 5.6蛋白质;（c）应激诱导型73-kD/pI 6.3蛋白质;（d）存在于内质网中的组成型74 - 78-kD蛋白质（葡萄糖调节蛋白）;和（e）存在于线粒体中的75-kD成员。尽管hsp70家族蛋白的生物学功能尚未完全了解，但已显示73-kD/pI 5.5蛋白在细胞内蛋白转运期间以ATP依赖性方式从胞吞囊泡中剥除网格蛋白晶格（5）。由于感染微生物的某些免疫显性蛋白是真核生物中热休克蛋白的同源物（6，7），目前的证据表明SLE中存在以前未描述的73-kD/pI自身抗体5。5组成型表达的hsp70家族成员与分子模拟的概念（8）一致，分子模拟是这种疾病中自身抗体诱导的机制。
Systemic lupus erythematosus (SLE) is characterized by the development and persistence of multiple autoantibodies to self-constituents. Detection of the presence of certain autoantibodies in patient serum is of considerable diagnostic utility, eg, anti-dsDNA and antibody to the Smith antigen, Sm (1). Autoantibodies in SLE also have been useful as probes to define the function of their target antigens in normal biological processes. For example, the observation that autoantibodies to Ul ribonucleoprotein inhibit mRNA splicing in vitro (2) provided some of the earliest evidence that Ul ribonucleoprotein is essential for splicing of mRNA precursors. The hsp70 family (3, 4) consists offive distinct, but structurally and immunologically related, proteins:(a) a constitutive 73-kD/pI 5.5 protein;(b) a stress-inducible 72-kD/pI 5.6 protein;(c) a stress-inducible 73-kD/pI 6.3 protein;(d) a constitutive 74-78-kD protein present in the endoplasmic reticulum (glucose-regulated protein); and (e) a 75-kD member present in the mitochondria. Although the biologic function of proteins in the hsp70 family is incompletely understood, the 73-kD/pI 5.5 protein has been shown to uncoat the clathrin lattice from endocytotic vesicles in an ATP-dependent manner during intracellular protein transport (5). Because certain immunodominant proteins of infecting microorganisms are homologues ofheat shock proteins in eukaryotes (6, 7), the present evidence for the existence in SLE of a previously undescribed autoantibody to the 73-kD/pI 5. 5 constitutively expressed member of the hsp70 family is consistent with the concept of molecular mimicry (8) as a mechanism for autoantibody induction in this disorder.