detailed characterization of autoantibodies in paraneoplastic pemphigus by phage display

通过噬菌体展示对副肿瘤性天疱疮自身抗体进行详细表征

• 批准号: 23591628
• 负责人: ISHII Ken
• 金额: $ 3.24万
• 依托单位: Toho University (2012-2013)Teikyo University (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591628/
• 关键词: 皮膚科学; 自己免疫性疾患; 細胞接着; 自己免疫; 天疱瘡; 自己抗体

To study the pathogenic mechanism of pareneoplastic pemphigus(PNP), we used phage display to clone monoclonal anti-Dsg3 antibodies from a PNP patient. We isolated 20 unique Dsg3-reactive mAbs, which we classified into four groups according to amino acid sequence. Pathogenic assay showed that three antibodies displayed pathogenic activity in blister formation with different potencies. Epitope mapping showed that these pathogenic mAbs bound Ca(2+)-dependent conformational epitopes in the middle portion of the extracellular region of Dsg3. These mAbs reflect the unique polyclonal nature of anti-Dsg3 antibodies in PNP and represent an important tool for detailing the pathophysiological mechanisms of blister formation in PNP.

为探讨副肿瘤性天疱疮(PNP)的发病机制，我们用噬菌体展示技术克隆了一例PNP患者的抗Dsg3单抗。我们分离了20株独有的Dsg3反应性单抗，并根据氨基酸序列将其分为四组。致病试验表明，三种抗体在水泡形成过程中表现出不同的致病活性。表位定位显示，这些致病单抗结合在Dsg3胞外区中部依赖于钙离子的构象表位。这些单抗反映了PNP中抗Dsg3抗体的独特的多克隆特性，是详细研究PNP中水泡形成的病理生理机制的重要工具。

项目成果

Human epidermal tight junctions are functional and allow penetration of activated Langerhans cell dendrites

人类表皮紧密连接具有功能性，可以穿透激活的朗格汉斯细胞树突

• 发表时间: 2011
• 作者: Keisuke Hotta;Yoshiki Higo;and Shinji Kusumoto;春山拓哉・草野修平・永次 史;Yoshida K
• 通讯作者: Yoshida K

What's new in bullous disease? What's new session

大疱性疾病有何新进展？

• 发表时间: 2011
• 作者: Y. Aoyama;K. Kamiya;O. Yamasaki;Y. Shirafuji;T. Hamada;S. Morizane;K. Fujii;A. Kubo;K. Iwatsuki;室慶直;Ishii K
• 通讯作者: Ishii K

Analysis of epitope profile of autoantibodies in pemphigus vulgaris using domain-swapped Dsg3/Dsg2 ELISAs

使用结构域交换 Dsg3/Dsg2 ELISA 分析寻常型天疱疮自身抗体的表位谱

• 发表时间: 2012
• 作者: Saleh M;Ken Ishii;Jun Yamagami;Takahisa Hachiya;Masayuki Amagai
• 通讯作者: Masayuki Amagai

Functional tight junction barrier localizes in the second layer of the stratum granulosum of human epidermis

• DOI: 10.1016/j.jdermsci.2013.04.021
• 发表时间: 2013-08-01
• 期刊: JOURNAL OF DERMATOLOGICAL SCIENCE
• 影响因子: 4.6
• 作者: Yoshida, Kazue;Yokouchi, Mariko;Kubo, Akiharu
• 通讯作者: Kubo, Akiharu

骨髄異形成症候群に合併した抗p200類天疱瘡の1例

抗p200类天疱疮合并骨髓增生异常综合征1例

• 发表时间: 2012
• 作者: Kazunori Masahata;Eiji Umemoto;Hisako Kayama;Manato Kotani;Shota Nakamura;Takashi Kurakawa;Junichi Kikuta;Kazuyoshi Gotoh;Daisuke Motooka;Shintaro Sato;Tomonori Higuchi;Yoshihiro Baba;Tomohiro Kurosaki;Makoto Kinoshita;Yosuke Shimada;Taishi;小原芙美子,橋本由起,漆畑真理,鷲崎久美子,石井健,関東裕美,石河晃
• 通讯作者: 小原芙美子,橋本由起,漆畑真理,鷲崎久美子,石井健,関東裕美,石河晃