CENP-O, a Protein Localized at the Centromere Throughout the Cell Cycle, Is a Novel Target Antigen in Systemic Sclerosis

CENP-O, a Protein Localized at the Centromere Throughout the Cell Cycle, Is a Novel Target Antigen in Systemic Sclerosis
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DOI:
10.3899/jrheum.080726
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发表时间:
2009-04
期刊:
The Journal of Rheumatology
影响因子:
--
通讯作者:
A. Saito;Y. Muro;K. Sugiura;M. Ikeno;K. Yoda;Y. Tomita
A. Saito;Y. Muro;K. Sugiura;M. Ikeno;K. Yoda;Y. Tomita
中科院分区:
其他
文献类型:
--
作者:
A. Saito;Y. Muro;K. Sugiura;M. Ikeno;K. Yoda;Y. Tomita

文献摘要

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目标。CENP-A、-B和-C是着丝粒的主要成分,也是抗着丝粒抗体的主要靶点。许多其他蛋白质也在间期细胞核的CENP-A核小体周围组装,形成间期着丝粒复合体(ICEN)。CENP-O蛋白是ICEN的一个组成部分,在整个细胞周期中定位于着丝粒。我们研究了CENP-O是否也被系统性自身免疫性疾病患者的血清靶向。方法。分析了114例ACA患者和142例非ACA患者的血清。采用Western blotting和细菌表达重组CENP-O蛋白的ELISA方法筛选抗CENP-O抗体的存在。此外,采用Western blotting HeLa细胞提取物检测抗cenp - o抗体阳性血清与主要着丝粒抗原的反应性。结果。4例女性ACA患者有抗cenp - o抗体。抗cenp - o抗体与特定的临床特征或其他血清学特征没有相关性。然而,4例患者中有1例表现出独特的硬皮病临床病程,其血清对CENP-O的反应性明显较高。结论。CENP-O蛋白是一种新的着丝粒抗原,被极少数aca阳性的硬皮病患者所识别。由于CENP-O是ICEN的组成部分,ICEN可能是系统性自身免疫中的一个大型抗原结构。
Objective. CENP-A, -B, and -C are major centromere components and the main targets of anticentromere antibodies (ACA). Many other proteins are also assembled around CENP-A nucleosomes in interphase nuclei to form the interphase centromere complex (ICEN). The CENP-O protein is a component of the ICEN that localizes at the centromere throughout the cell cycle. We investigated whether CENP-O is also targeted by sera from patients with systemic autoimmune diseases. Methods. Sera from 114 patients with ACA and 142 patients without ACA were analyzed. Western blotting and an ELISA with bacterially expressed recombinant CENP-O protein were performed to screen for the presence of anti-CENP-O antibodies. In addition, anti-CENP-O antibody-positive sera were tested by Western blotting HeLa cell extracts to examine reactivity with the major centromere antigens. Results. Four female patients with ACA had anti-CENP-O antibodies. There was no correlation of anti-CENP-O antibodies with specific clinical features or other serological features. However, one of the 4 patients, who showed a unique clinical course of scleroderma, had sera with markedly high reactivity to CENP-O. Conclusion. CENP-O protein is a novel centromere antigen that is recognized by a very minor population of ACA-positive patients with scleroderma. Because CENP-O is an ICEN component, ICEN may be a large antigenic structure in systemic autoimmunity.