Basic studies for the pathogenesis and diagnosis of the autoimmune bullous diseases

自身免疫性大疱性疾病发病机制及诊断的基础研究

• 批准号: 05044186
• 负责人: NISHIKAWA Takeji
• 金额: $ 3.52万
• 依托单位: Keio Gijuku University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05044186/
• 关键词: Autoimmune bullous disease,; Pemphigus,; Bullous pemphigoid,; Dermatitis herpetiformis,; Desmosome,; Molecular biology,; Desmoglein,; Recombinant protein; 類天疱瘡; 線状IgA皮膚症; 自己抗原; 免疫電顕

There are a number of autoimmune blistering diseases. We have investigated various aspects in these diseases under a collaborative basis with many investigators in foreign institutes. Nishikawa T,Amagai M and Hashimoto T have been abroad in a past year, exchanged various materials for experiments and established a number of collaborative projects. Particularly, the antigens for various types of pemphiqus and various antigens for IgA antibodies in sera of either dermatitis herpetiformis and linear IgA dermatosis have been studied extensively with Dr.John R.Stanley and Dr.John J.Zone, respectively. With Dr.Stanley in NIH,U.S., We investigated on the pemphiqus vulgaris antigen and the pemphigus foliaceus antigen (desmoglein). Using their cDNA and baculovirus expression system, we produced recombinant proteins for both the pemphigus vulgaris antigen and the pemphigus foliaceus antigen (desmoglein) with proper conformation. Absorption of the pathogenic antibodies in the sera of both pemphig … More us vulgaris and pemphigus foliaceus patients was confirmed by the experiments that the treatment of the sera with these recombinant baculoproteins inhibit completely blister formation in newborn mouse animal experiment. This indicates the possibility of new therapy of antigen specific affinity column using these recombinant proteins. With Dr.Zone in Utah University, U.S., we studied on diseases in which IgA antibodies are involved. We analyzed a Japanese case with rare fibrillar type of dermatitis herpetiformis, in particular on various IgA autoantibodies. Furthermore, we investigated on the autoantigens for linear IgA bullous dermatosis, and found that most common antigen seems to be a 97 kD protein which is present in the epidermal side of the 1M NaCl split skin. Very recently, we have also found that the 290 kD epidermolysis bullosa acquisita antigen is recognized by some linear IgA bullous dermatosis sera. These collaborative researches should further provide us with many new insights for the progress in both diagnosis and therapy in various autoimmune skin diseases in the future. Less

有许多自身免疫性起泡疾病。我们与国外研究机构的许多研究人员合作，对这些疾病的各个方面进行了研究。西川T、天井M、桥本T在过去的一年里，在国外交流了各种实验材料，并建立了许多合作项目。特别地，JohnR.Stanley博士和JohnJ.Zone博士分别对疱疹样皮炎和线性伊加皮肤病血清中各种天疱疮的抗原和伊加抗体的各种抗原进行了广泛的研究.和美国国立卫生研究院的斯坦利博士一起，我们研究了寻常型天疱疮抗原和落叶型天疱疮抗原（桥粒芯糖蛋白）。利用它们的cDNA和杆状病毒表达系统，我们生产了具有适当构象的寻常型天疱疮抗原和落叶型天疱疮抗原（桥粒芯糖蛋白）的重组蛋白。两种天疱疮患者血清中病原抗体的吸收 ...更多信息 在新生小鼠动物实验中，用这些重组杆状蛋白处理血清完全抑制水疱形成的实验证实了寻常型和落叶型天疱疮患者。这表明利用这些重组蛋白进行新的抗原特异性亲和柱治疗的可能性。与美国犹他州大学的Zone博士一起，我们研究了与伊加抗体有关的疾病。我们分析了一个日本病例与罕见的纤维型疱疹样皮炎，特别是各种伊加自身抗体。此外，我们研究了线性伊加大疱性皮肤病的自身抗原，发现最常见的抗原似乎是存在于1M NaCl分裂皮肤的表皮侧的97kD蛋白。最近，我们还发现290 kD获得性大疱性表皮病抗原被一些线性伊加大疱性皮肤病血清识别。这些合作研究将为今后各种自身免疫性皮肤病的诊断和治疗提供新的思路。少

项目成果

Mariko SEISHIMA: "Pemphigus IgG,but not bullous pemphigoid IgG,Causes a transient increase in intracellular calcium and inositol 1,4,5-trisp-hate in DJM-1 cells,a squamous cell carcinoma line." J Invest Dermatol. 104. 33-37 (1995)

Mariko SEISHIMA：“天疱疮 IgG，但不是大疱性类天疱疮 IgG，会导致鳞状细胞癌细胞系 DJM-1 细胞中细胞内钙和肌醇 1,4,5-trisp-hate 短暂增加。”

Seiji KAWANA: "Change in clinical features,histologic finding,and antigen profiles with development of pemphigus foliaceus from pemphigus vulgaris." Arch Dermatol. 130. 1534-1538 (1994)

Seiji KAWANA：“随着寻常型天疱疮发展为落叶型天疱疮，临床特征、组织学发现和抗原谱发生变化。”

Tadeusz P.CHORZELSKI: "Atypical pemphigus associated with malignant thymoma and autoimmune response restricted to 170 kD antigen:is it a variant of para neoplastic pemphigus?" Eur J Dermatol. 5. 31-35 (1995)

Tadeusz P.CHORZELSKI：“与恶性胸腺瘤和仅限于 170 kD 抗原的自身免疫反应相关的非典型天疱疮：它是副肿瘤性天疱疮的变体吗？”

Mariko SEISHIMA: "Pemphigus IgG,but not bullous pemphigoid IgG,causes a transient increase in intracellular calcium and inositol 1,4,5-trisphate in Djj-1 cells, a squamous cell carcinoma line." J Invest Dermatol. 104. 33-37 (1995)

Mariko SEISHIMA：“天疱疮 IgG，而非大疱性类天疱疮 IgG，会导致鳞状细胞癌细胞系 Djj-1 细胞中细胞内钙和肌醇 1,4,5-三磷酸盐的短暂增加。”

Yukiko NISHIBORI: "Paraneoplastic pemphigus:The first case report from Japan." Dermatology. (in press).

Yukiko NISHIBORI：“副肿瘤性天疱疮：来自日本的第一个病例报告。”