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有丝分裂纺锤体装置的两个主要自身抗原-抗体系统。

Two major autoantigen-antibody systems of the mitotic spindle apparatus.

作者信息

Andrade L E, Chan E K, Peebles C L, Tan E M

机构信息

W. M. Keck Autoimmune Disease Center, Scripps Research Institute, La Jolla, California 92037, USA.

出版信息

Arthritis Rheum. 1996 Oct;39(10):1643-53. doi: 10.1002/art.1780391006.

Abstract

OBJECTIVE

To characterize human autoantigen-antibody systems related to the mitotic poles and spindles.

METHODS

Thirty-seven human sera with autoantibodies staining mitotic poles and spindles in indirect immunofluorescence (IIF) studies were further characterized by immunofluorescence on mitotic cells and by immunoblotting and immunoprecipitation. Clinical diagnoses meeting the American College of Rheumatology criteria were based on chart review and interview with the corresponding physicians.

RESULTS

Two autoantibody systems reactive with mitotic poles and spindles were defined. Type 1 nuclear mitotic apparatus (NuMA-1) antibodies were identified in the serum of 30 patients. Interphase cells showed a fine, speckled, nuclear staining, while mitotic cells had bright staining of the rim of the centrosomes and light staining of the spindles proximal to the centrosomes. In telophase, the staining shifted from the centrosomes to the reforming nuclei. On immunoblotting, anti-NuMA-1 sera reacted with a 210-kd protein. The reactivity of these sera was identified (with the aid of reference antibodies) as the previously described NuMA antigen-antibody system. Clinical information was available for only 17 of the 30 patients with anti-NuMA-1; of these, 17 (53%) had clinical and lip biopsy findings that met the criteria for Sjögren's syndrome. NuMA-2 antibodies were found in the sera of 7 patients. Interphase cells showed no nuclear or cytoplasmic staining, but mitotic cells had brightly stained poles and spindles. At anaphase/telophase, staining shifted to the midbody and the intercellular bridge. Anti-NuMA-2 sera immunoprecipitated a protein of 116 kd. This group of patients was more heterogeneous and had both systemic and organ-specific autoimmune diseases.

CONCLUSIONS

NuMA protein (here called NuMA-1) and a 116-kd protein (here called NuMA-2) are the major targets of the autoimmune response in the mitotic apparatus, since most of the selected sera (based on IIF staining of the mitotic spindles and poles) recognized 1 of these 2 antigens.

摘要

目的

对与有丝分裂极和纺锤体相关的人类自身抗原 - 抗体系统进行特征描述。

方法

在间接免疫荧光(IIF)研究中,对37份能使有丝分裂极和纺锤体染色的含自身抗体的人血清,通过对有丝分裂细胞进行免疫荧光检测、免疫印迹和免疫沉淀进一步进行特征分析。符合美国风湿病学会标准的临床诊断基于病历审查和与相应医生的访谈。

结果

确定了两种与有丝分裂极和纺锤体反应的自身抗体系统。在30例患者血清中鉴定出1型核有丝分裂器(NuMA - 1)抗体。间期细胞显示出精细的、斑点状的核染色,而有丝分裂细胞的中心体边缘有明亮染色,中心体近端的纺锤体有浅色染色。在末期,染色从中心体转移到正在重新形成的细胞核。在免疫印迹中,抗NuMA - 1血清与一种210kd的蛋白质反应。借助参考抗体确定这些血清的反应性为先前描述的NuMA抗原 - 抗体系统。30例抗NuMA - 1患者中仅有17例有临床信息;其中17例(53%)有符合干燥综合征标准的临床和唇活检结果。在7例患者血清中发现了NuMA - 2抗体。间期细胞未显示核或细胞质染色,但有丝分裂细胞的极和纺锤体有明亮染色。在后期/末期,染色转移到中间体和细胞间桥。抗NuMA - 2血清免疫沉淀出一种116kd的蛋白质。这组患者更为异质性,既有系统性自身免疫疾病,也有器官特异性自身免疫疾病。

结论

NuMA蛋白(此处称为NuMA - 1)和一种116kd的蛋白质(此处称为NuMA - 2)是有丝分裂器自身免疫反应的主要靶点,因为大多数所选血清(基于有丝分裂纺锤体和极的IIF染色)识别这两种抗原中的一种。

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