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利用重组表位研究自身免疫性甲状腺疾病中抗甲状腺过氧化物酶自身抗体的异质性。

Use of recombinant epitopes to study the heterogeneous nature of the autoantibodies against thyroid peroxidase in autoimmune thyroid disease.

作者信息

Zanelli E, Henry M, Malthiery Y

机构信息

Laboratoire de Biochimie Médicale, INSERM U38, Faculté de Médecine, Marseille, France.

出版信息

Clin Exp Immunol. 1992 Jan;87(1):80-6. doi: 10.1111/j.1365-2249.1992.tb06417.x.

DOI:10.1111/j.1365-2249.1992.tb06417.x
PMID:1370775
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1554233/
Abstract

Microsomal antigen is often recognized by the sera from patients with autoimmune thyroid disease (AITD). Human thyroid peroxidase (hTPO) is the main component of this antigen. In a previous study, we expressed hTPO cDNA as fusion proteins in prokaryotic vector; we thereby defined seven antigenic peptides by using two rabbit polyclonal anti-hTPO antibodies. In the present study we used the seven epitopes and three widened peptides to define the reactivity pattern of 61 sera from patients with AITD. Thirty-eight of them reacted against at least one of the seven hTPO-restricted epitopes; 14 were negative against the seven determinants but recognized one or two of the extended peptides. Thus, the antibody response against hTPO appeared to be highly heterogeneous in AITD patient sera. Moreover, we demonstrated that the immunodetection of the hTPO on Western blotting with deoxycholate solubilized microsomes can be perfectly correlated with the recognition of one of the epitopes in the region 554-735.

摘要

微粒体抗原常被自身免疫性甲状腺疾病(AITD)患者的血清识别。人甲状腺过氧化物酶(hTPO)是该抗原的主要成分。在先前的研究中,我们在原核载体中表达hTPO cDNA作为融合蛋白;通过使用两种兔多克隆抗hTPO抗体,我们确定了7个抗原肽。在本研究中,我们使用这7个表位和3个延伸肽来确定61例AITD患者血清的反应模式。其中38例对7个hTPO限制性表位中的至少一个有反应;14例对这7个决定簇呈阴性,但识别出一或两个延伸肽。因此,AITD患者血清中针对hTPO的抗体反应似乎高度异质性。此外,我们证明用脱氧胆酸盐溶解的微粒体在蛋白质印迹法上对hTPO的免疫检测与对554 - 735区域中一个表位的识别完全相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce43/1554233/b6310b7faa65/clinexpimmunol00051-0083-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce43/1554233/b6310b7faa65/clinexpimmunol00051-0083-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce43/1554233/b6310b7faa65/clinexpimmunol00051-0083-a.jpg

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Structural features of the autoantigens involved in thyroid autoimmune disease: the thyroid microsomal/microvillar antigen.参与甲状腺自身免疫性疾病的自身抗原的结构特征:甲状腺微粒体/微绒毛抗原。
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Structure-activity analysis of microsomal antigen/thyroid peroxidase.微粒体抗原/甲状腺过氧化物酶的构效分析
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Antibodies against denatured and reduced thyroid microsomal antigen in autoimmune thyroid disease.
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Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs.人甲状腺过氧化物酶:完整的cDNA和蛋白质序列、染色体定位以及两种可变剪接mRNA的鉴定
Proc Natl Acad Sci U S A. 1987 Aug;84(16):5555-9. doi: 10.1073/pnas.84.16.5555.
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Porcine thyroid peroxidase: relationship between the native enzyme and an active, highly purified tryptic fragment.
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