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针对大疱性类天疱疮抗原1(BPAg 1)的人源单克隆自身抗体。

Human monoclonal autoantibodies specific for the bullous pemphigoid antigen 1 (BPAg 1).

作者信息

Peyron E, Nicolas J F, Réano A, Roche P, Thivolet J, Haftek M, Schmitt D, Péronne C, Banchereau J, Rousset F

机构信息

Inserm U346, Dermatology Clinic, Edouard Herriot Hospital, Lyon, France.

出版信息

J Immunol. 1994 Aug 1;153(3):1333-9.

PMID:8027561
Abstract

Bullous pemphigoid (BP) is an acquired blistering skin disease associated with the production of IgG autoantibodies to the 230-kDa BP Ag (BPAg1). To better characterize the epitopes of BPAg1, we generated immortalized B cell lines secreting human mAbs (HumAbs) to BPAg1 from two BP patients whose sera reacted with native BPAg1 but not with a recombinant BP55 carboxyl-terminal peptide. Ab-producing B cell lines were established by EBV infection of CD40-activated PBMCs. Three independent clonal lines were obtained that secreted IgG HumAbs, including one IgG1 kappa (BP3) and two distinct IgG4 kappa (BP1 and BP2). These three HumAbs immunoprecipitated BPAg1. Blocking immunofluorescence experiments and phylogenetic studies showed that these Abs recognize different epitopes of BPAg1. This analysis with HumAbs further extends the serologic demonstration of the wide variety of epitopes recognized by BPAg1 autoantibodies which contrasts with the limited number of epitopes recognized by thyroid peroxidase monoclonal autoantibodies.

摘要

大疱性类天疱疮(BP)是一种获得性水疱性皮肤病,与针对230-kDa BP抗原(BPAg1)产生IgG自身抗体有关。为了更好地表征BPAg1的表位,我们从两名BP患者中生成了分泌针对BPAg1的人源单克隆抗体(HumAbs)的永生化B细胞系,这两名患者的血清与天然BPAg1反应,但不与重组BP55羧基末端肽反应。通过EBV感染CD40激活的外周血单核细胞(PBMC)建立产生抗体的B细胞系。获得了三个独立的克隆系,它们分泌IgG HumAbs,包括一个IgG1 κ(BP3)和两个不同的IgG4 κ(BP1和BP2)。这三种HumAbs免疫沉淀了BPAg1。阻断免疫荧光实验和系统发育研究表明,这些抗体识别BPAg1的不同表位。用HumAbs进行的这项分析进一步扩展了BPAg1自身抗体识别的多种表位的血清学证明,这与甲状腺过氧化物酶单克隆自身抗体识别的有限数量的表位形成对比。

相似文献

1
Human monoclonal autoantibodies specific for the bullous pemphigoid antigen 1 (BPAg 1).针对大疱性类天疱疮抗原1(BPAg 1)的人源单克隆自身抗体。
J Immunol. 1994 Aug 1;153(3):1333-9.
2
[Study of epitopic sites of the major bullous pemphigoid antigen (BPAg1)].[大疱性类天疱疮主要抗原(BPAg1)表位的研究]
Ann Biol Clin (Paris). 1995;53(4):193-7.
3
Human autoantibodies against the 230-kD bullous pemphigoid antigen (BPAG1) bind only to the intracellular domain of the hemidesmosome, whereas those against the 180-kD bullous pemphigoid antigen (BPAG2) bind along the plasma membrane of the hemidesmosome in normal human and swine skin.针对230-kD大疱性类天疱疮抗原(BPAG1)的人类自身抗体仅与半桥粒的细胞内结构域结合,而针对180-kD大疱性类天疱疮抗原(BPAG2)的自身抗体则在正常人和猪的皮肤中沿着半桥粒的质膜结合。
J Clin Invest. 1993 Apr;91(4):1608-15. doi: 10.1172/JCI116368.
4
IgE autoantibodies directed against the major bullous pemphigoid antigen in patients with a severe form of pemphigoid.针对严重型类天疱疮患者主要大疱性类天疱疮抗原的IgE自身抗体。
J Immunol. 1996 Oct 15;157(8):3642-7.
5
IgG antibodies from patients with bullous pemphigoid bind to localized epitopes on synthetic peptides encoded by bullous pemphigoid antigen cDNA.大疱性类天疱疮患者的IgG抗体与大疱性类天疱疮抗原cDNA编码的合成肽上的局部表位结合。
J Immunol. 1990 Dec 1;145(11):3728-33.
6
Autoantibodies to bullous pemphigoid antigen 180 induce dermal-epidermal separation in cryosections of human skin.针对大疱性类天疱疮抗原180的自身抗体在人皮肤冰冻切片中诱导真皮-表皮分离。
J Invest Dermatol. 2002 Apr;118(4):664-71. doi: 10.1046/j.1523-1747.2002.01720.x.
7
Antibody to bullous pemphigoid antigen 1 binds to the antigen at perilesional but not uninvolved skin, in localized bullous pemphigoid.在局限性大疱性类天疱疮中,抗大疱性类天疱疮抗原1抗体在皮损周围皮肤而非未受累皮肤与该抗原结合。
Eur J Dermatol. 1999 Jan-Feb;9(1):39-42.
8
Immunofluorescence-negative bullous pemphigoid sera contain antibodies mostly directed against the 180 kDa bullous pemphigoid antigen (BPAg2).免疫荧光阴性的大疱性类天疱疮血清所含抗体大多针对180 kDa大疱性类天疱疮抗原(BPAg2)。
Br J Dermatol. 1997 Aug;137(2):306-7.
9
[Molecular heterogeneity of the bullous pemphigoid antigen as detected by immunoblotting].[免疫印迹法检测大疱性类天疱疮抗原的分子异质性]
Nihon Hifuka Gakkai Zasshi. 1989 Jul;99(8):871-5.
10
Difference in binding sites of autoantibodies against 230- and 170-kD bullous pemphigoid antigens on salt-split skin.盐裂皮肤表面针对230kD和170kD大疱性类天疱疮抗原的自身抗体结合位点的差异
J Invest Dermatol. 1994 May;102(5):686-90. doi: 10.1111/1523-1747.ep12374252.

引用本文的文献

1
IgG4-mediated autoimmune diseases: a niche of antibody-mediated disorders.IgG4 相关自身免疫性疾病:抗体介导性疾病的一个亚类。
Ann N Y Acad Sci. 2018 Feb;1413(1):92-103. doi: 10.1111/nyas.13561. Epub 2018 Jan 28.
2
Generation of Human B-Cell Lines Dependent on CD40-Ligation and Interleukin-4.依赖CD40连接和白细胞介素-4的人B细胞系的产生
Front Immunol. 2015 Feb 11;6:55. doi: 10.3389/fimmu.2015.00055. eCollection 2015.
3
IgE antibodies in sera from patients with bullous pemphigoid are autoantibodies preferentially directed against the 230-kDa epidermal antigen (BP230).
大疱性类天疱疮患者血清中的IgE抗体是优先针对230kDa表皮抗原(BP230)的自身抗体。
J Clin Immunol. 1998 May;18(3):202-9. doi: 10.1023/a:1020531005776.