Olivry Thierry, Joubeh Sohaila, Dunston Stanley M, Nishiyama Takafumi, Ghohestani Reza F
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Exp Dermatol. 2003 Apr;12(2):198-203. doi: 10.1046/j.0906-6705.2002.072.x.
Pemphigus vulgaris (PV) is an autoimmune blistering skin disease of humans and companion animals. In human patients, PV is associated with the production of IgG autoantibodies specific for keratinocyte desmosomal glycoproteins of the cadherin family. The purpose of this study was to determine whether antikeratinocyte IgG autoantibodies were present in the skin and serum of dogs with PV, and also to identify the canine PV autoantigen(s) targeted by circulating autoantibodies. Eleven dogs were selected because of the microscopic demonstration of suprabasal epithelial acantholysis. Direct immunofluorescence revealed the presence of IgG autoantibodies bound to the membrane of keratinocytes in skin biopsy specimens of 8/9 dogs (89%). Using indirect immunofluorescence, serum-circulating IgG autoantibodies were found in 10/11 (91%) and 5/11 (45%) dogs, using normal canine gingiva and cultured canine oral keratinocytes, respectively. By immunoblotting using cultured canine oral keratinocyte protein lysates, IgG autoantibodies from 7/9 (78%) tested dogs recognized a 130-kDa antigen that comigrated with that identified by rabbit polyclonal antibodies raised against desmoglein-3. This 130 kDa antigen was confirmed to represent the canine equivalent of human desmoglein-3 by immunoprecipitation-immunoblotting. The results of these studies provide evidence that the canine desmoglein-3 homologue is a major autoantigen in dogs with PV. These observations further establish spontaneous canine PV as a natural model for research on pathogenesis, etiology and novel therapeutic approaches for this disease of humans.
寻常型天疱疮（PV）是一种发生于人类和伴侣动物的自身免疫性水疱性皮肤病。在人类患者中，PV与针对钙黏蛋白家族角质形成细胞桥粒糖蛋白的IgG自身抗体的产生有关。本研究的目的是确定患有PV的犬的皮肤和血清中是否存在抗角质形成细胞IgG自身抗体，并鉴定循环自身抗体所靶向的犬PV自身抗原。由于显微镜下显示基底上棘层松解，选择了11只犬。直接免疫荧光显示，8/9只（89%）犬的皮肤活检标本中存在与角质形成细胞膜结合的IgG自身抗体。使用间接免疫荧光法，分别以正常犬牙龈和培养的犬口腔角质形成细胞为抗原，在10/11只（91%）和5/11只（45%）犬中发现了血清循环IgG自身抗体。通过使用培养的犬口腔角质形成细胞蛋白裂解物进行免疫印迹，7/9只（78%）受试犬的IgG自身抗体识别出一种130 kDa的抗原，该抗原与用抗桥粒芯糖蛋白-3兔多克隆抗体制备的抗体所识别的抗原迁移位置相同。通过免疫沉淀-免疫印迹证实，这种130 kDa的抗原代表犬的桥粒芯糖蛋白-3。这些研究结果提供了证据，表明犬桥粒芯糖蛋白-3同源物是患有PV的犬的主要自身抗原。这些观察结果进一步确立了自发性犬PV作为研究人类这种疾病的发病机制、病因和新治疗方法的天然模型。
