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

有许多自身免疫性水疱疾病。我们在与国外许多研究机构合作的基础上，研究了这些疾病的各个方面。Nishikawa T，Amagai M和Hashimoto T在过去的一年里一直在国外，交换各种材料进行实验，并建立了多个合作项目。特别是，Dr.John R.Stanley和Dr.John J.Zone分别对各种类型的天疱疮抗原和疱疹样皮炎和线性IgA皮肤病血清中IgA抗体的各种抗原进行了广泛的研究。与美国国立卫生研究院的stanley博士合作我们对寻常型天疱疮抗原和叶型天疱疮抗原进行了研究。利用他们的cDNA和杆状病毒表达系统，我们获得了具有正确构象的天疱疮抗原和天疱疮叶状抗原（桥蛋白）的重组蛋白。在新生小鼠动物实验中，用这些重组杆状蛋白处理天疱疮和叶状天疱疮患者的血清，证实了病原菌抗体的吸收，完全抑制了新生小鼠的水疱形成。这提示了利用这些重组蛋白进行抗原特异性亲和柱治疗的可能性。我们与美国犹他大学的Dr.Zone一起研究了与IgA抗体有关的疾病。我们分析了一例日本罕见的纤原性疱疹样皮炎，特别是各种IgA自身抗体。此外，我们研究了线状IgA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裂皮表皮侧的97 kD蛋白。最近，我们还发现290 kD大疱性表皮松解抗原被一些线性IgA大疱性皮肤病血清识别。这些合作研究将进一步为我们今后在各种自身免疫性皮肤病的诊断和治疗方面的进展提供许多新的见解。少

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