Evidence for multiple shared antigenic determinants within Ro60 and other lupus-related ribonucleoprotein autoantigens in human autoimmune responses
Evidence for multiple shared antigenic determinants within Ro60 and other lupus-related ribonucleoprotein autoantigens in human autoimmune responses
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DOI：
10.4049/jimmunol.175.11.7669
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发表时间：
2005-12-01
影响因子：
4.4
通讯作者：
Fu, SM
中科院分区：
文献类型：
--
作者：
Pal, R;Deshmukh, US;Fu, SM
针对几种核糖核蛋白（RNP）Ag的Ab反应是系统性红斑狼疮（SLE）的特征性特征。在我们实验室使用小鼠模型系统的先前工作已经揭示了核糖核蛋白之间的表位扩散和固有的交叉反应性有助于在自身免疫血清中观察到的多种特异性。我们现在已经将这些研究扩展到人类自身免疫反应。使用纯化的多克隆抗体和来自SLE患者的单克隆抗体，Ro 60和SmD之间的交叉反应性被证明。交叉反应性表位定位于Ro 60（481-505）和SmD 88 -102上的非同源区域。五个单克隆抗体特异性识别凋亡细胞，表现出可变水平的交叉反应性对其他非同源核糖核蛋白的目标和绑定多个，非重叠和非同源表位的Ro 60。我们的研究表明，经常针对自身抗原之间的交叉反应是人类系统性自身免疫反应的一个重要方面。Ro 60上多个交叉反应表位的存在对于SLE患者和未显示临床疾病证据的正常个体中抗Ro 60 Ab的产生可能是重要的。
Ab responses directed against several ribonucleoprotein (RNP) Ags are a characteristic feature of systemic lupus erythematosus (SLE). Previous work in our laboratory using mouse model systems had revealed that both epitope spreading and inherent cross-reactivity between ribonucleoproteins contributes to the observed multiple specificities in autoimmune sera. We have now extended these studies to human autoimmune responses. Using purified polyclonal and mAbs derived from SLE patients, crossreactivity between Ro60 and SmD was demonstrated. The cross-reactive epitope was mapped to nonhomologous regions on Ro60(481-505) and SmD88-102. Five mAbs specifically recognized apoptotic cells, demonstrated variable levels of cross-reactivity toward other nonhomologous ribonucleoprotein targets and bound multiple, nonoverlapping and nonhomologous epitopes on Ro60. Our study demonstrates that cross-reactivity between frequently targeted autoantigens is an important aspect of human systemic autoimmune responses. The presence of multiple cross-reactive epitopes on Ro60 might be important for the generation of anti-Ro60 Ab in SLE patients and in normal individuals displaying no evidence of clinical disease.